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A Children's Oncology Group clinical trial aimed to determine if bortezomib (B) increased the efficacy of ifosfamide and vinorelbine (IV) in paediatric Hodgkin lymphoma (HL). This study enrolled 26 relapsed HL patients (<30 years) treated with two to four cycles of IVB. The primary endpoint was anatomic complete response (CR) after two cycles. Secondary endpoints included overall response (OR: CR + partial response) at study completion compared to historical controls [72%; 95% confidence interval (CI): 59-83%]. Although few patients achieved the primary objective, OR with IVB improved to 83% (95% CI: 61-95%; p = 0.32). Although not statistically different, results suggest IVB may be a promising combination.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Adulto , Ácidos Borônicos/administração & dosagem , Bortezomib , Criança , Pré-Escolar , Intervalo Livre de Doença , Humanos , Ifosfamida/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Pirazinas/administração & dosagem , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , Vinorelbina , Adulto JovemRESUMO
BACKGROUND: We assessed the safety and efficacy of ifosfamide and vinorelbine (IV) as a less toxic and effective reinduction regimen for pediatric patients with relapsed or refractory Hodgkin Lymphoma. PROCEDURE: This multi-center Children's Oncology Group phase II pilot study enrolled patients <30 years of age with biopsy-proven Hodgkin Lymphoma in relapse or refractory disease after front-line therapy. Treatment consisted of ifosfamide 3,000 mg/m(2) intravenous infusion over 24 hr on Days 1-4 and vinorelbine 25 mg/m(2) /dose intravenous push on Days 1 and 5 of each 21 day cycle with cytokine support. The study endpoints included estimation of key toxicities (cardiac, hepatic, or renal toxicity or toxic death), the rate of successful peripheral stem cell harvesting, and response after two cycles of therapy. RESULTS: Sixty-six patients received a median of two cycles of IV. Sixty-four of 66 were heavily pretreated, 4 had refractory disease, 55% were male and 79% had nodular sclerosis HL. The primary toxicities were hematologic. Harvested peripheral stem cells were sufficient for autologous transplantation in 46 of 54 patients for whom stem cell collection was attempted. The overall response rate (72%; 95% CI 59-83%) permitted the majority of patients to undergo subsequent stem cell transplantation. CONCLUSIONS: IV is a safe and effective re-induction regimen for salvage of pediatric patients with relapsed or refractory Hodgkin Lymphoma with an excellent response rate and success of post chemotherapy stem cell harvest. It avoids the use of etoposide, an agent associated with secondary malignancy after stem cell transplantation.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Doença de Hodgkin/terapia , Recidiva Local de Neoplasia/terapia , Transplante de Células-Tronco de Sangue Periférico , Terapia de Salvação , Adolescente , Adulto , Criança , Pré-Escolar , Terapia Combinada , Feminino , Seguimentos , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Ifosfamida/administração & dosagem , Lactente , Recém-Nascido , Masculino , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Projetos Piloto , Prognóstico , Indução de Remissão , Taxa de Sobrevida , Transplante Autólogo , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , Vinorelbina , Adulto JovemRESUMO
STUDY OBJECTIVE: To evaluate the disposition of pentoxifylline and its metabolite, lisofylline, in New Zealand rabbits after two alternative routes of administration, intranasal and intratracheal. DESIGN: Pharmacokinetics study in an animal model. SETTING: University-affiliated animal care facility. SUBJECTS: Twenty New Zealand white rabbits divided into four groups of five rabbits each: group 1 did not receive study drug (control group), and groups 2, 3, and 4 evaluated intravenous, intranasal, and intratracheal routes of administration, respectively. INTERVENTION: Each rabbit in groups 2-4 received pentoxifylline as a single 20-mg/kg dose by their respective route of administration. MEASUREMENTS AND MAIN RESULTS: Blood samples were collected over a 24-hour period and were analyzed by using high-performance liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters evaluated were area under the concentration-time curve from time zero extrapolated to infinity (AUC(0-infinity)), maximum concentration (Cmax), time to maximum concentration (Tmax), elimination rate constant (k(el)), and half-life (t1/2). Median pentoxifylline pharmacokinetic parameters after intravenous administration were AUC(0-infinity) 5420 ng x hr/ml, Cmax 16,727 ng/ml, Tmax 5 minutes, k(el) 0.036 minute(-1), and t1/2 19 minutes. Median pharmacokinetic parameters after intranasal and intratracheal administration, respectively, were AUC(0-infinity) 4224 and 6824 ng x hr/ml, Cmax 11,181 and 16,758 ng/ml, Tmax 5 and 5 minutes, k(el) 0.028 and 0.032 minute(-1), and t1/2 25 and 22 minutes. The metabolite, lisofylline, displayed a similar disposition after the three different routes of administration. CONCLUSION: The pharmacokinetic profiles after intranasal and intratracheal administration of pentoxifylline appear similar to those after intravenous administration. These data provide support for development of pentoxifylline intranasal and intratracheal dosage formulations that would be suitable for use in premature neonates.
Assuntos
Pentoxifilina/análogos & derivados , Adjuvantes Imunológicos , Animais , Área Sob a Curva , Cromatografia Líquida de Alta Pressão , Vias de Administração de Medicamentos , Meia-Vida , Taxa de Depuração Metabólica , Pentoxifilina/administração & dosagem , Pentoxifilina/sangue , Pentoxifilina/farmacocinética , Farmacocinética , Coelhos , Espectrometria de Massas em TandemRESUMO
BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the success of a faculty Research/Writing Group (RWG) by quantifying the amount of scholarly productivity from participants in the group compared with that of a matched cohort. EDUCATIONAL ACTIVITY AND SETTING: The RWG meets monthly to discuss current projects, providing an assessment of their scholarly activity. Participants offer ideas on improvement, resources and possible platforms for presentations and/or publications. FINDINGS: To evaluate the success of this model, scholarly production from the participants in the RWG was compared to a matched group of clinical non-tenure track faculty not participating in the group over a three year period. Faculty perception of RWG participation was evaluated by data collected through a survey using Qualtrics. SUMMARY: Participation in the RWG provided these junior faculty the support system to feel confident in their pursuit of scholarly activities; and therefore, they outpaced their counterparts in dissemination of their research.
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Pesquisa Biomédica , Docentes de Farmácia/estatística & dados numéricos , Escrita Médica , Comunicação Acadêmica/estatística & dados numéricos , Emprego/classificação , Processos Grupais , Humanos , Mentores , Comunicação Acadêmica/tendênciasRESUMO
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer and the leading cause of cancer-related death in children and adolescents. Minimal residual disease (MRD) is a strong, independent prognostic factor. The objective of this study was to identify molecular signatures distinguishing patients with positive MRD from those with negative MRD in different subtypes of ALL, and to identify molecular networks and biological pathways deregulated in response to positive MRD at day 46. We compared gene expression levels between patients with positive MRD and negative MRD in each subtype to identify differentially expressed genes. Hierarchical clustering was applied to determine their functional relationships. We identified subtype-specific gene signatures distinguishing patients with positive MRD from those with negative MRD. We identified the genes involved in cell cycle, apoptosis, transport, and DNA repair. We also identified molecular networks and biological pathways dysregulated in response to positive MRD, including Granzyme B, B-cell receptor, and PI3K signaling pathways.
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OBJECTIVE: To describe the implementation of a student research program and to provide outcomes from the initial 4 years' experience. DESIGN: Students conducted individual research projects in a 4-year longitudinal program (known as Pathway), with faculty member advising and peer mentoring. A prospective assessment compared perceptions of those who completed the Pathway program with those of students who did not. Descriptive statistics, t tests, and analysis of variance (ANOVA) were used. ASSESSMENT: The class of 2013 was the first to complete the Pathway program. In the Pathway assessment project, 59% (n=47) of students who responded reached self-set goals. Pathway students agreed that this research experience improved their ability to work/think independently, evaluate literature, and distinguish themselves from other students. CONCLUSION: The Pathway program helped students understand the research process and reach other self-set goals.
Assuntos
Educação em Farmácia/métodos , Pesquisa , Estudantes de Farmácia , Competência Clínica , Currículo , Avaliação Educacional , Docentes , Humanos , Estudos Longitudinais , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: The purpose of this study was to assess children's comprehension of a new assent booklet, (K(id)S(ent)), which uses pictures and written information. STUDY DESIGN: A randomized, crossover study evaluated the comprehension of assent documents by children, 7 to 11 years of age at a local elementary school. The two types of documents tested were the standard assent form and the K(id)S(ent) Assent Booklet. Participants were randomized as to which test document they received first by using a cluster randomization design. Participants read the document and then took a short quiz. The process was repeated for the other document on a separate day. Study participants were assigned a percentage score and a binary perfect score for each quiz. Mixed effects logistic and linear regression models with random intercepts were applied to the continuous percent quiz scores and binary perfect quiz scores, respectively. RESULTS: A total of 190 participants completed the standard quiz, and 195 students completed the booklet quiz. A statistically significant difference in perfect quiz scores (p=0.004) and percent quiz scores (p≤0.001) between booklet and standard form was noted. CONCLUSIONS: The quiz scores may indicate that the style of document is not the only factor influencing participant understanding.
RESUMO
Extrinsic staining of teeth due to excessive iron intake has been reported previously in the literature. We describe a 7-month-old infant who presented with extrinsic teeth staining due to inadvertent over consumption of dietary iron. The infant was fed iron-fortified formula and rice cereal. Rice cereal, fortified with iron, was being used as part of a normal infant diet and as a thickening agent when added to the formula for treatment of gastroesophageal reflux. After several months of administration, "blackening" of the infant's teeth was noted by the mother. The stain was removed by the pediatric dentist who simply scraped the affected teeth. No further staining occurred after the amount of dietary iron was reduced.
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OBJECTIVES: To evaluate graduating pharmacy students' perceptions of their preparedness for advanced pharmacy practice experiences and the effectiveness of problem-based learning in their preparation. METHODS: A survey instrument was administered anonymously in May 2004 and May 2005 to graduating pharmacy students of the University of Mississippi School of Pharmacy. RESULTS: Students reported that the areas in which problem-based learning prepared them most effectively for advanced pharmacy practice experiences were retrieval of medical information (80%), discussion of disease states and drug therapies at the basic science level (56%), and evaluation of the appropriateness of a medication regimen based on patient specific information (50%). Areas in which students reported being inadequately prepared included identifying and utilizing drug assistance programs (42%) and processing prescriptions/hospital orders (40%). CONCLUSION: Data from 2 consecutive graduating classes supports that problem-based learning is an effective format for preparing pharmacy students for advanced pharmacy practice experiences in a variety of areas.
Assuntos
Aprendizagem Baseada em Problemas/métodos , Estudantes de Farmácia , Currículo , Coleta de Dados , Humanos , Seleção de Pacientes , Estudantes de Medicina , Ensino/métodosRESUMO
OBJECTIVES: To determine whether implementing a rotating facilitator structure provides a reliable method of assessing group participation and assigning grades to third-professional year pharmacy students in a problem-based learning curriculum. DESIGN: In the 2004-2005 school year, a "one block, one facilitator" structure was replaced by a "weekly rotating facilitator" structure. Each student received a grade from the assigned facilitator each week. The 8 weekly grades were then averaged for a final course grade. Student grades were reviewed weekly and at the end of each block. Facilitators and students completed survey instruments at the end of each of four 8-week blocks. ASSESSMENT: Student grades were reviewed, and the class average was compared to the class averages from the 2 previous years. For example, in block I the class average was 86 which compared to averages of 88 and 87 for 2002-03 and 2003-04 respectively. Survey data revealed a 40% agreement by facilitators in block I that student performance was improved compared to student performance prior to this change. This agreement increased to 71%, 72%, and 71% respectively for blocks II - IV. Student survey data at the end of the academic year supported weekly facilitator rotation and revealed that a majority of students agreed that exposure to a variety of facilitators enhanced their group participation. CONCLUSION: As confirmed by student grades and student and faculty members' feedback, the change to a rotating facilitator structure resulted in a reliable method of assigning student grades for group participation.