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1.
Artigo em Inglês | MEDLINE | ID: mdl-31929386

RESUMO

Acute lymphoblastic leukemia is the most common malignancy in children. Long-term survival exceeds 90%; however, therapy-induced toxicity remains a concern. Methotrexate neurotoxicity (MTX-NT) is common, often necessitating alterations in chemotherapy regimens. Dextromethorphan has been used as an abortive and prophylactic treatment for MTX-NT. The authors report a case series of 7 pediatric patients with acute lymphoblastic leukemia with prior episodes of MTX-NT given a single dose of dextromethorphan (1 to 2 mg/kg) on the day of MTX administration and 7 days later. No subsequent episodes of MTX-NT occurred after 40 intravenous and 81 intrathecal administrations. This specific regimen of secondary prophylaxis may prevent MTX-NT.

2.
Clin Pediatr (Phila) ; 58(1): 50-59, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30296841

RESUMO

Patient experience is positively associated with superior medical outcomes, clinical quality, patient safety measures, physician job satisfaction, doctor-patient communication, and patient compliance with treatment recommendations. A concrete pediatrics-focused methodology for improving patient experience in a multispecialty ambulatory setting has not been described, nor has the impact on practice outcomes been assessed. The primary aim of this study was to improve patient experience care provider scores at a single multiclinic children's hospital in the Midwest to the 70th percentile in a 5-year period. The secondary aim sought to determine the impact of quality improvement efforts on practice growth, patient complaint rate, and provider/staff engagement. Patient experience was measured by returned Press-Ganey surveys. Interventions involved establishing infrastructure, promoting feedback and transparency, providing education, and transforming culture. Provider scores improved from the 19th to the 70th percentile within 5 years. Practice volume increased by 17.1%; patient complaint/grievance frequency decreased 33-fold; and provider/staff engagement did not appreciably change.


Assuntos
Hospitais Pediátricos/estatística & dados numéricos , Ambulatório Hospitalar/normas , Satisfação do Paciente/estatística & dados numéricos , Relações Médico-Paciente , Melhoria de Qualidade , Pesquisa sobre Serviços de Saúde , Humanos , Inquéritos e Questionários
3.
Cancer ; 125(6): 963-971, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30521100

RESUMO

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm characterized by the presence of abnormal CD1a-positive (CD1a+ )/CD207+ histiocytes. Hemophagocytic lymphohistiocytosis (HLH) represents a spectrum of hyperinflammatory syndromes typified by the dysregulated activation of the innate and adaptive immune systems. Patients with LCH, particularly those with multisystem (MS) involvement, can develop severe hyperinflammation mimicking that observed in HLH. Nevertheless, to the authors' knowledge, little is known regarding the prevalence, timing, risk factors for development, and outcomes of children and young adults who develop HLH within the context of MS-LCH (hereafter referred to LCH-associated HLH). METHODS: To gain further insights, the authors conducted a retrospective, multicenter study and collected data regarding all patients diagnosed with MS-LCH between 2000 and 2015. RESULTS: Of 384 patients with MS-LCH, 32 were reported by their primary providers to have met the diagnostic criteria for HLH, yielding an estimated 2-year cumulative incidence of 9.3% ± 1.6%. The majority of patients developed HLH at or after the diagnosis of MS-LCH, and nearly one-third (31%) had evidence of an intercurrent infection. Patient age <2 years at the time of diagnosis of LCH; female sex; LCH involvement of the liver, spleen, and hematopoietic system; and a lack of bone involvement each were found to be independently associated with an increased risk of LCH-associated HLH. Patients with MS-LCH who met the criteria for HLH had significantly poorer 5-year survival compared with patients with MS-LCH who did not meet the criteria for HLH (69% vs 97%; P < .0001). CONCLUSIONS: Given its inferior prognosis, further efforts are warranted to enhance the recognition and optimize the treatment of patients with LCH-associated HLH.


Assuntos
Sistema Hematopoético/imunologia , Histiocitose de Células de Langerhans/complicações , Fígado/imunologia , Linfo-Histiocitose Hemofagocítica/epidemiologia , Baço/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Sistema Hematopoético/patologia , Histiocitose de Células de Langerhans/imunologia , Humanos , Lactente , Recém-Nascido , Fígado/patologia , Linfo-Histiocitose Hemofagocítica/imunologia , Masculino , Prognóstico , Estudos Retrospectivos , Baço/patologia , Adulto Jovem
4.
Ochsner J ; 18(4): 332-338, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30559617

RESUMO

Background: Patient perception of care is positively associated with better medical outcomes, clinician job satisfaction, and fewer malpractice claims and also has significant downstream economic impact for healthcare organizations. A sparse amount of data exists regarding provider and practice characteristics driving high levels of patient experience in the pediatric hematology-oncology (PHO) ambulatory setting. The aims of this study were to determine key drivers of high care provider ratings and of the likelihood of recommending our ambulatory PHO practice. Methods: Patient experience was measured using the Consumer Assessment of Healthcare Providers and Systems Clinician & Group Survey (CG-CAHPS). The study outcomes were to determine the survey items most associated with top-box scores for "Rate This Provider" and for "Likelihood of Your Recommending Our Practice to Others." Results: The survey items Explanations the care provider gave you about your problem or condition and Concern the care provider showed for your questions or worries were most strongly correlated with high provider ratings. How well the staff worked together to care for you and Friendliness/courtesy of nurse/assistant were most strongly correlated with the likelihood of recommending the practice. Conclusion: High provider ratings were most associated with the physician's ability to explain problems and conditions to families. Staff teamwork and nursing attitude were most associated with patient recommendations of the PHO practice. By identifying key drivers of high provider and practice ratings by patients in the PHO ambulatory setting, a targeted approach with a focus on physician-specific communication attributes, teamwork, and nursing attitude can be deployed to improve the patient experience.

5.
Mol Cancer Ther ; 17(5): 1079-1089, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29483210

RESUMO

Germ cell tumors (GCT) are malignant tumors that arise from pluripotent embryonic germ cells and occur in children and young adults. GCTs are treated with cisplatin-based regimens which, while overall effective, fail to cure all patients and cause significant adverse late effects. The seminoma and nonseminoma forms of GCT exhibit distinct differentiation states, clinical behavior, and response to treatment; however, the molecular mechanisms of GCT differentiation are not fully understood. We tested whether the activity of the mTORC1 and MAPK pathways were differentially active in the two classes of GCT. Here we show that nonseminomatous germ cell tumors (NSGCT, including embryonal carcinoma, yolk sac tumor, and choriocarcinoma) from both children and adults display activation of the mTORC1 pathway, while seminomas do not. In seminomas, high levels of REDD1 may negatively regulate mTORC1 activity. In NSGCTs, on the other hand, EGF and FGF2 ligands can stimulate mTORC1 and MAPK signaling, and members of the EGF and FGF receptor families are more highly expressed. Finally, proliferation of NSGCT cells in vitro and in vivo is significantly inhibited by combined treatment with the clinically available agents erlotinib and rapamycin, which target EGFR and mTORC1 signaling, respectively. These results provide an understanding of the signaling network that drives GCT growth and a rationale for therapeutic targeting of GCTs with agents that antagonize the EGFR and mTORC1 pathways. Mol Cancer Ther; 17(5); 1079-89. ©2018 AACR.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Receptores ErbB/antagonistas & inibidores , Alvo Mecanístico do Complexo 1 de Rapamicina/antagonistas & inibidores , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Linhagem Celular Tumoral , Receptores ErbB/metabolismo , Cloridrato de Erlotinib/administração & dosagem , Humanos , Subunidade gama Comum de Receptores de Interleucina/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Embrionárias de Células Germinativas/metabolismo , Sirolimo/administração & dosagem , Neoplasias Testiculares/genética , Neoplasias Testiculares/metabolismo , Carga Tumoral/efeitos dos fármacos
6.
J Oncol Pract ; 11(5): 416-20, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26130818

RESUMO

PURPOSE: The study of patient satisfaction is a rapidly emerging area of importance within health care. High levels of patient satisfaction are associated with exceptional physician-patient communication, superior patient compliance, reduced risk of medical malpractice, and economic benefit in the value-based purchasing era. To our knowledge, no previous reports have evaluated methods to improve the patient experience within the pediatric hematology-oncology (PHO) outpatient clinic. METHODS: Patient satisfaction was measured using returned Press-Ganey surveys at Blank Children's Hospital PHO outpatient clinic (UnityPoint Health). The aim of this study was to raise the overall patient satisfaction score to the 75th percentile and raise the care provider score (CP) to the 90th percentile nationally. After analyzing data from 2013, interventions were implemented in January 2014, including weekly review of returned surveys, review of goals and progress at monthly staff meetings, distribution of written materials addressing deficiencies, score transparency among providers, provider use of Web-based patient satisfaction training modules, devotion of additional efforts to address less satisfied demographics (new patient consultations), and more liberal use of service recovery techniques. RESULTS: In the PHO outpatient clinic, overall patient satisfaction improved from the 56th to 97th percentile. Care provider scores improved from the 70th to 99 th percentile. For new patients, overall satisfaction improved from the 27th to 92 nd percentile, and care provider scores improved from the 29th to 98 th percentile. CONCLUSION: Patient satisfaction was improved in a midsize PHO clinic by implementing provider- and staff-driven initiatives. A combination of minor behavioral changes among care providers and staff in conjunction with systems-related modifications drove improvement.


Assuntos
Satisfação do Paciente , Instituições de Assistência Ambulatorial , Hematologia , Humanos , Oncologia , Pediatria
7.
Neonatal Netw ; 32(5): 316-22, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23985469

RESUMO

Rectal bleeding in neonates is an alarming sign that suggests a possible serious underlying condition, such as infection or bleeding disorder that would necessitate hospitalization and prompt intervention. We report a case of eosinophilic gastroenteritis caused by cow's milk protein allergy in a one-day- old infant, who presented with frankly bloody stools associated with massive gastrointestinal and peripheral blood eosinophilia prior to initiation of enteral feedings. The patient's outcome was favorable, with complete spontaneous recovery in one week, after a period of bowel rest, parenteral nutrition, and use of amino acid formula. The eosinophilia was also transient and gradually resolving by two months of age. Rectal bleeding secondary to allergic colitis caused by cow's milk sensitization may occur in neonates, and failure to appreciate this possibility may lead to inappropriate diagnostic or therapeutic intervention.


Assuntos
Enterite/imunologia , Enterite/enfermagem , Eosinofilia/imunologia , Eosinofilia/enfermagem , Gastrite/imunologia , Gastrite/enfermagem , Hipersensibilidade a Leite/imunologia , Hipersensibilidade a Leite/enfermagem , Proteínas do Leite/imunologia , Efeitos Tardios da Exposição Pré-Natal/imunologia , Efeitos Tardios da Exposição Pré-Natal/enfermagem , Biópsia , Diagnóstico Diferencial , Endoscopia Gastrointestinal/enfermagem , Enterite/diagnóstico , Eosinofilia/diagnóstico , Feminino , Mucosa Gástrica/patologia , Gastrite/diagnóstico , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/enfermagem , Hemorragia Gastrointestinal/patologia , Humanos , Recém-Nascido , Mucosa Intestinal/patologia , Hipersensibilidade a Leite/diagnóstico , Triagem Neonatal/enfermagem , Diagnóstico de Enfermagem , Gravidez , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Efeitos Tardios da Exposição Pré-Natal/patologia
8.
BMC Cancer ; 13: 313, 2013 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-23806198

RESUMO

BACKGROUND: Aberrant DNA methylation is a prominent feature of many cancers, and may be especially relevant in germ cell tumors (GCTs) due to the extensive epigenetic reprogramming that occurs in the germ line during normal development. METHODS: We used the Illumina GoldenGate Cancer Methylation Panel to compare DNA methylation in the three main histologic subtypes of pediatric GCTs (germinoma, teratoma and yolk sac tumor (YST); N = 51) and used recursively partitioned mixture models (RPMM) to test associations between methylation pattern and tumor and demographic characteristics. We identified genes and pathways that were differentially methylated using generalized linear models and Ingenuity Pathway Analysis. We also measured global DNA methylation at LINE1 elements and evaluated methylation at selected imprinted loci using pyrosequencing. RESULTS: Methylation patterns differed by tumor histology, with 18/19 YSTs forming a distinct methylation class. Four pathways showed significant enrichment for YSTs, including a human embryonic stem cell pluripotency pathway. We identified 190 CpG loci with significant methylation differences in mature and immature teratomas (q < 0.05), including a number of CpGs in stem cell and pluripotency-related pathways. Both YST and germinoma showed significantly lower methylation at LINE1 elements compared with normal adjacent tissue while there was no difference between teratoma (mature and immature) and normal tissue. DNA methylation at imprinted loci differed significantly by tumor histology and location. CONCLUSION: Understanding methylation patterns may identify the developmental stage at which the GCT arose and the at-risk period when environmental exposures could be most harmful. Further, identification of relevant genetic pathways could lead to the development of new targets for therapy.


Assuntos
Metilação de DNA/genética , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Embrionárias de Células Germinativas/patologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem
9.
Proc Natl Acad Sci U S A ; 108(32): 13153-8, 2011 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-21775673

RESUMO

Germ-cell tumors (GCTs), which arise from pluripotent embryonic germ cells, exhibit a wide range of histologic differentiation states with varying clinical behaviors. Although testicular GCT is the most common cancer of young men, the genes controlling the development and differentiation of GCTs remain largely unknown. Through a forward genetic screen, we previously identified a zebrafish mutant line, tgct, which develops spontaneous GCTs consisting of undifferentiated germ cells [Neumann JC, et al. (2009) Zebrafish 6:319-327]. Using positional cloning we have identified an inactivating mutation in alk6b, a type IB bone morphogenetic protein (BMP) receptor, as the cause of the zebrafish GCT phenotype. Alk6b is expressed in spermatogonia and early oocytes, and alk6b mutant gonads display impaired BMP signal transduction, altered expression of BMP target genes, and abnormal germ-cell differentiation. We find a similar absence of BMP signaling in undifferentiated human GCTs, such as seminomas and embryonal carcinoma, but not in normal testis or in differentiated GCTs. These results indicate a germ-cell-autonomous role for BMP signal transduction in germ-cell differentiation, and highlight the importance of the BMP pathway in human GCTs.


Assuntos
Receptores de Proteínas Morfogenéticas Ósseas Tipo I/genética , Diferenciação Celular/genética , Células Germinativas/patologia , Mutação/genética , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Embrionárias de Células Germinativas/patologia , Peixe-Zebra/genética , Alelos , Animais , Sequência de Bases , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/metabolismo , Clonagem Molecular , Feminino , Loci Gênicos/genética , Células Germinativas/metabolismo , Humanos , Masculino , Meiose , Dados de Sequência Molecular , Ovário/metabolismo , Ovário/patologia , Transdução de Sinais , Espermatozoides/metabolismo , Espermatozoides/patologia , Neoplasias Testiculares/genética , Neoplasias Testiculares/patologia , Testículo/metabolismo , Testículo/patologia
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