RESUMO
INTRODUCTION: Delayed methotrexate clearance in several patients admitted to the oncology unit at a regional medical center necessitated the development of a pharmacist-driven protocol for supportive therapy with high-dose methotrexate. This performance improvement project evaluated the impact of the protocol on inpatient length of stay, patient safety, and clinical outcomes. METHODS: Retrospective data were collected over 14 months pre-implementation and prospective data were collected over 19 months post-implementation. Primary outcomes included mean length of stay and incidence of kidney injury. Secondary outcomes included myelosuppression, treatment delays, mucositis, protocol adherence, and pharmacist interventions. Chi-squared and unpaired two sample t-test were used for data analysis. INTERVENTION: A literature review of consensus recommendations for supportive care post high-dose methotrexate administration was conducted to develop the protocol. Education on implementation was provided to involved disciplines. RESULTS: One-hundred ten high-dose methotrexate admissions for 23 patients were analyzed: 24 pre-protocol and 86 post-protocol. Mean length of stay was 5.17 nights pre-protocol and 3.91 nights post-protocol (p = 0.026). Incidence of kidney injury significantly decreased (16.7% pre-protocol versus 3.5% post-protocol; p = 0.0394). Lower incidences of all-grade anemia (83.3% versus 58.1%), neutropenia (62.5% versus 29.1%), and thrombocytopenia (58.3% versus 33.7%) as well as treatment delays (29.2% versus 11.6%; p = 0.036) were reported post protocol. No statistically significant difference in mucositis was detected. Pharmacist adherence to protocol was ≥80% resulting in 348 interventions with 99.4% provider acceptance. CONCLUSION: The implementation of a pharmacist-driven high-dose methotrexate management protocol resulted in a statistically significant decrease in inpatient length of stay and kidney injury. Further studies are needed to assess the impact on additional outcomes.
Assuntos
Antimetabólitos/administração & dosagem , Antimetabólitos/uso terapêutico , Conduta do Tratamento Medicamentoso , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Neoplasias/tratamento farmacológico , Farmacêuticos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Idoso , Antimetabólitos/efeitos adversos , Estudos de Coortes , Feminino , Fidelidade a Diretrizes , Humanos , Incidência , Tempo de Internação , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Thiopurine S-methyltransferase (TPMT) testing, either by genotyping or phenotyping, can reduce the incidence of adverse severe myelotoxicity episodes induced by azathioprine. The comparative cost-effectiveness of TPMT genotyping and phenotyping are not known. OBJECTIVE: Our aim was to assess the cost-effectiveness of phenotyping-based dosing of TPMT activity, genotyping-based screening and no screening (reference) for patients treated with azathioprine. METHODS: A decision tree was built to compare the conventional weight-based dosing strategy with phenotyping and with genotyping using a micro-simulation model of patients with inflammatory bowel disease from the perspective of the French health care system. The time horizon was set up as 1 year. Only direct medical costs were used. Data used were obtained from previous reports, except for screening test and admission costs, which were from real cases. The main outcome was the cost-effectiveness ratios, with an effectiveness criterion of one averted severe myelotoxicity episode. RESULTS: The total expected cost of the no screening strategy was 409/patient, the total expected cost of the phenotyping strategy was 427/patient, and the total expected cost of the genotyping strategy was 476/patient. The incremental cost-effectiveness ratio was 2602/severe myelotoxicity averted in using the phenotyping strategy, and 11,244/severe myelotoxicity averted in the genotyping strategy compared to the no screening strategy. At prevalence rates of severe myelotoxicity > 1%, phenotyping dominated genotyping and conventional strategies. CONCLUSION: The phenotype-based strategy to screen for TPMT deficiency dominates (cheaper and more effective) the genotype-based screening strategy in France. Phenotype-based screening dominates no screening in populations with a prevalence of severe myelosuppression due to azathioprine of > 1%.
Assuntos
Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/genética , Genótipo , Metiltransferases/genética , Modelos Biológicos , Fenótipo , Erros Inatos do Metabolismo da Purina-Pirimidina/diagnóstico , Erros Inatos do Metabolismo da Purina-Pirimidina/genética , Antimetabólitos/química , Antimetabólitos/farmacologia , Antimetabólitos/uso terapêutico , Azatioprina/química , Azatioprina/farmacologia , Azatioprina/uso terapêutico , Análise Custo-Benefício , Hipersensibilidade a Drogas/tratamento farmacológico , Hipersensibilidade a Drogas/metabolismo , Testes Genéticos/economia , Testes Genéticos/métodos , Variação Genética , Humanos , Metiltransferases/metabolismo , Erros Inatos do Metabolismo da Purina-Pirimidina/tratamento farmacológico , Erros Inatos do Metabolismo da Purina-Pirimidina/metabolismoRESUMO
AIM: To evaluate the cost-effectiveness of trifluridine and tipiracil hydrochloride (FTD/TPI) compared with best supportive care (BSC) or regorafenib for the treatment of patients with metastatic colorectal cancer who have been previously treated with or are not considered candidates for available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF agents and anti-EGFR agents in Greece. METHODS: A partitioned survival model was locally adapted from a third-party payer perspective over a 10 year time horizon. Efficacy data and utility values were extracted from published studies. Resource consumption data were obtained from local experts using a questionnaire developed for the purpose of the study and was combined with unit costs obtained from official sources. All costs reflect the year 2017 in euros. Primary outcomes were patients' life years (LYs), quality-adjusted life years (QALYs), total costs and incremental cost-effectiveness ratios (ICERs) per QALY and LYs gained. RESULTS: Total life time cost per patient for FTD/TPI, BSC and regorafenib was estimated to be 10,087, 1,879 and 10,850, respectively. In terms of health outcomes, FTD/TPI was associated with 0.25 and 0.11 increment in LYs compared with BSC and regorafenib, respectively. Furthermore, FTD/TPI was associated with 0.17, and 0.07 increment in QALYs compared with BSC and regorafenib, resulting in ICERs of 32,759 per LY gained and 49,326 per QALY gained versus BSC. Moreover, FTD/TPI was a dominant alternative over regorafenib. CONCLUSION: The results indicate that FTD/TPI may represent a cost-effective treatment option compared with other alternative therapies as a third-line treatment of metastatic colorectal cancer in Greece.
Assuntos
Neoplasias Colorretais/tratamento farmacológico , Análise Custo-Benefício/estatística & dados numéricos , Pirrolidinas/economia , Pirrolidinas/uso terapêutico , Timina/economia , Timina/uso terapêutico , Trifluridina/economia , Trifluridina/uso terapêutico , Adulto , Antimetabólitos/economia , Antimetabólitos/uso terapêutico , Neoplasias Colorretais/patologia , Análise Custo-Benefício/economia , Grécia , Humanos , Análise de SobrevidaRESUMO
INTRODUCCIÓN: El presente informe expone la evaluación de tecnología sobre la eficacia y seguridad de mifamurtida, para el tratamiento de pacientes con osteosarcoma (OS) osteoblástico no metastásico sin tratamiento sistémico previo, en el contexto de neoadyuvancia com quimioterapia MAPI (metotrexato, doxorrubicina, cisplatino e ifosfamida). El osteosarcoma (OS) es un tumor maligno primario del esqueleto y la neoplasia primaria más común del hueso en niños y adultos jóvenes. Representa aproximadamente el 20% de todos los tumores óseos primarios malignos y el 0.2% de todos los tumores malignos. Su curva de distribución en cuanto a la edad es bimodal, con un primer pico en la adolescencia y otro después de los 65 años. La adición de quimioterapia agresiva adyuvante o neoadyuvante a la cirugía há mejorado considerablemente el pronóstico de los pacientes con enfermedad localizada, incrementando la tasa de curación de pacientes con OS en las extremidades y sin enfermedad metastásica evidente de 10-15% a 50-70%. OBJETIVO: El presente dictamen preliminar expone la evaluación de la tecnología sanitaria de la eficacia y seguridad de mifamurtida, para el tratamiento de pacientes com osteosarcoma (OS) osteoblástico no metastásico sin tratamiento sistémico previo, en el contexto de neoadyuvancia con quimioterapia MAPI (metotrexato, doxorrubicina, cisplatino e ifosfamida). TECNOLOGIA SANITARIA DE INTERES: La mifamurtida (Mepact, Takeda) es un compuesto químico biológicamente activo con actividad inmunomoduladora, clasificándose como un adyuvante biológico y perteneciente al grupo farmacoterapéutico de los inmunoestimulantes (36,37) . El compuesto es un derivado totalmente sintético del muramil dipéptido (MDP), el estimulante inmunológico natural más pequeño de las paredes celulares de micobacterias (37) . Al igual que la MDP, la mifamurtida es reconocida por el receptor de reconocimiento de patrones NOD2, localizado en varios tipos de glóbulos blancos, principalmente monocitos y macrófagos. De tal manera, mifamurtida simula una infección bacteriana, resultando en una activación de los macrófagos y un incremento en la producción de TNF-alfa, interleuquina 1, 6, 8 y 12, y moléculas de adhesión (e.g., ICAM-1 y LFA-1). METODOLOGÍA: Se llevó a cabo una búsqueda sistemática de la literatura con respecto a la eficacia y seguridad del uso de mifamurtida para el tratamiento de pacientes con osteosarcoma osteoblástico no metastásico sin tratamiento sistémico previo, en el contexto de neoadyuvancia con quimioterapia MAPI (metotrexato, doxorrubicina, cisplatino e ifosfamida). La búsqueda se realizó utilizando las bases de datos: National Library of Medicine (PubMed, 09/2017), Web of Science (WoS, 09/2017), y Centre for Reviews and Dissemination (CRD, 09/2017). Adicionalmente, se amplió la búsqueda revisando la evidencia generada por grupos internacionales que realizan revisiones sistemáticas (RS), evaluaciones de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC), tales como The Cochrane Library (09/2017), The National Institute of Health and Care Excellence (NICE, 08/2017) del Reino Unido, The National Guidelines of Clearinghouse (NGC, 08/2017) de los Estados Unidos, The Scottish Intercollegiate Guidelines Network (SIGN, 08/2017) de Escocia, Australian Clinical Practice Guidelines (08/2017), The Royal Children's Hospital Melbourne Practice Guidelines de Australia (08/2017), CMA Infobase de la Canadian Medical Association (08/2017), American College of Physicians Clinical Practice Guidelines and Recommendations (08/2017) de los Estados Unidos, Guidelines International Network (GIN, 08/2017), New Zealand Guidelines Group (NZGG, 08/2017) de Nueva Zelanda, Guía Salud de España (08/2017, 08/2017), y el Centro Nacional de Excelencia Tecnológica en Salud (CENETEC) de México. Esta búsqueda se completo revisando publicaciones de grupos dedicados a la educación, investigación y mejora de la práctica clínica oncológica dentro de América y Europa, como The National Comprehensive Cancer Network (NCCN, 09/2017) de los Estados Unidos, y The European Society for Medical Oncology (ESMO, 08/2017). Por último, se completó la búsqueda ingresando a la página web www.clinicaltrials.gov, para así poder identificar ensayos clínicos en elaboración o que no hayan sido publicados aún, y así disminuir el riesgo de sesgo de publicación. RESULTADOS: se llevó a cabo una búsqueda bibliográfica y de evidencia científica hasta setiembre de 2017 relacionada al uso de mifamurtida en el tratamiento de pacientes con osteosarcoma (OS) osteoblástico no metastásico sin tratamiento sistémico previo, en el contexto de neoadyuvancia con quimioterapia MAPI (metotrexato, doxorrubicina, cisplatino e ifosfamida). Según las guías consultadas para pacientes con OS no metastásico resecable, referentes al uso de mifamurtida como parte del régimen quimioterapéutico MAPI neoadyuvante (pre-operatorio), no existen recomendaciones generales, unicamente algunas hacen mención al uso de mifamurtida en un contexto de adyuvancia (post-operatorio). El único ensayo clínico que evalúa el uso de mifamurtida dentro del régimen quimioterapéutico MAPI, lo hace en un contexto adyuvante, el cual reporta que no hubo una mejora estadísticamente significativa en relación a la sobreviva libre de eventos (HR 0.78, IC 95%: 0.54 1.2; p=0.22). Por otro lado, si bien se observó una aparente mejora en relación a la sobrevida global (HR 0.71; IC 95%, 0.52 0.96, valor p no reportado), es de notar que el límite superior del intervalo de confianza es marginal con respecto al valor nulo de no significancia estadística y que el valor p no ha sido reportado. Asimismo, estos resultados son invalidados por i) interacción observada entre mifamurtida y quimioterapia, afectando el análisis marginal del ensayo, ii) falta de poder estadístico para comparar individualmente los cuatro regímenes quimioterapéuticos evaluados, y iii) aparente falta de poder estadístico para evaluar el efecto de mifamurtida a los regímenes quimioterapéuticos sobre la sobrevida global. Actualmente, no se ha identificado ningún estudio publicado o en proceso dirigido a evaluar los efectos de la mifamurtida neoadyuvante en población con diagnóstico de OS no metastásico. Por lo tanto, no existe evidencia respecto a la eficacia y seguridad de mifamurtida en un contexto pre-operatorio. Se requiere de un ensayo clínico que evalúe la administración de mifamurtida, prévio a la resección del tumor, en la población de interés del presente dictamen. CONCLUSIÓN: El Instituto de Evaluación de Tecnologías en Salud e Investigación-IETSI no aprueba el uso de mifamurtida para el manejo de los pacientes com diagnóstico de osteosarcoma (OS) osteoblástico no metastásico sin tratamento sistémico en el contexto de neoadyuvancia con quimioterapia MAPI.
Assuntos
Humanos , Doxorrubicina/uso terapêutico , Acetilmuramil-Alanil-Isoglutamina/análogos & derivados , Acetilmuramil-Alanil-Isoglutamina/uso terapêutico , Cisplatino/uso terapêutico , Ifosfamida/uso terapêutico , Antimetabólitos/uso terapêutico , Avaliação da Tecnologia Biomédica , Osteossarcoma/tratamento farmacológico , Análise Custo-Benefício , Quimioterapia CombinadaRESUMO
INTRODUÇÃO: Leucodermias solares geram preocupações estéticas para os pacientes e nenhum tratamento é primeira escolha na literatura. MÉTODOS: Ensaio clínico randomizado, monocego. Foram selecionados nove pacientes, com presença de pelo menos 10 lesões de leucodermia em cada antebraço, totalizando 180 lesões. Avaliou-se a eficácia de 2 sessões do MMP® com 5-Fluoracil comparado com MMP® sem medicação e 5-Fluoracil intralesional para tratamento das leucodermias de antebraços. RESULTADOS: Das lesões avaliadas segundo a eficácia, todas apresentaram repigmentação, o que indica melhora clínica com qualquer dos 3 tratamentos. O 5-FU isolado foi o mais eficaz, com significância estatística, seguido do MMP®+5-FU. O MMP® sem medicação foi o menos eficaz. Dentre os efeitos adversos, hiperpigmentação, ardor, prurido e dor não tiveram significância estatística ao fim do estudo. O eritema do MMP®+5-FU foi significativamente superior na maioria das visitas. Todos os pacientes relataram melhora clínica após os procedimentos. Maior relato de dor com a técnica de MMP® com ou sem medicação. DISCUSSÃO: A melhor eficácia do 5-FU em relação ao MMP®+5-Fluoracil poderia ser explicada pela diferente técnica de aplicação da medicação. Supõe-se que o MMP® foi o menos eficaz devido a não utilização do 5-FU. Não existem na literatura trabalhos com o uso de 5-FU intralesional ou MMP®+5-FU ou MMP® isolado para tratar leucodermias solares. O eritema persistente do MMP®+5-FU seria resultado do trauma somado a reação inflamatória induzida pelo 5-FU. CONCLUSÃO: Após 2 sessões de tratamento, o 5-FU mostrou-se o mais eficaz e com maior tolerabilidade pelos pacientes. Descritores: Leucodermia solar; 5-Fluoracil; MMP®; Dermatologia
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Sistemas de Liberação de Medicamentos/instrumentação , Hipopigmentação/terapia , Fluoruracila/uso terapêutico , Microinjeções , Agulhas , Antimetabólitos/uso terapêutico , Prurido/etiologia , Urticária/etiologia , Medição da Dor , Injeções Intradérmicas , Resultado do Tratamento , Sistemas de Liberação de Medicamentos/efeitos adversos , Hiperpigmentação/etiologia , Eritema/etiologia , Fluoruracila/administração & dosagem , Microinjeções/efeitos adversos , Antimetabólitos/administração & dosagemRESUMO
D-cycloserine (DCS), an FDA approved anti-tuberculosis drug has extensively been studied for its cognitive enhancer effects in psychiatric disorders. DCS may enhance the effects of fear extinction trainings in animals during exposure therapy and hence we investigated the effects of DCS on distinct behavioral parameters in a predator odor stress model and tested the optimal duration for repeated daily administrations of the agent. Cat fur odor blocks were used to produce stress and avoidance and risk assessment behavioral parameters were used where DCS or saline were used as treatments in adjunct to extinction trainings. We observed that DCS facilitated extinction training by providing further extinction of avoidance responses, risk assessment behaviors and increased the contact with the cue in a setting where DCS was administered before extinction trainings for 3 days without producing a significant tolerance. In amygdala and hippocampus, GluN1 protein expressions decreased 72h after the fear conditioning in the traumatic stress group suggesting a possible down-regulation of NMDARs. We observed that extinction learning increased GluN1 proteins both in the amygdaloid complex and the dorsal hippocampus of the rats receiving extinction training or extinction training with DCS. Our findings also indicate that DCS with extinction training increased GluN1 protein levels in the frontal cortex. We may suggest that action of DCS relies on enhancement of the consolidation of fear extinction in the frontal cortex.
Assuntos
Antimetabólitos/uso terapêutico , Aprendizagem da Esquiva/efeitos dos fármacos , Ciclosserina/uso terapêutico , Lobo Frontal/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/metabolismo , Transtornos de Estresse Traumático/tratamento farmacológico , Análise de Variância , Animais , Gatos , Modelos Animais de Doenças , Extinção Psicológica/efeitos dos fármacos , Feminino , Reação de Congelamento Cataléptica/efeitos dos fármacos , Lobo Frontal/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Odorantes , Ratos , Ratos Wistar , Reflexo de Estiramento/efeitos dos fármacos , Medição de Risco , Transtornos de Estresse Traumático/patologia , Transtornos de Estresse Traumático/fisiopatologiaRESUMO
This report represents a further update of the consensus panel criteria for the assessment of clinical response in patients with Waldenström macroglobulinaemia (WM). These criteria have been updated in light of further data demonstrating an improvement in categorical responses with new drug regimens as well as acknowledgement of the fact that such responses are predictive of overall outcome. A number of key changes are proposed but challenges do however remain and these include the variability in kinetics of immunoglobulin M (IgM) reduction with different treatment modalities and the apparent discrepancy between IgM and bone marrow/tissue response noted with some regimens. Planned sequential bone marrow assessments are encouraged in clinical trials.
Assuntos
Macroglobulinemia de Waldenstrom/tratamento farmacológico , Anticorpos Monoclonais/sangue , Anticorpos Monoclonais/uso terapêutico , Antimetabólitos/uso terapêutico , Exame de Medula Óssea/métodos , Exame de Medula Óssea/normas , Ácidos Borônicos/uso terapêutico , Bortezomib , Densitometria , Progressão da Doença , Intervalo Livre de Doença , Previsões , Hematopoese , Humanos , Cadeias Leves de Imunoglobulina/sangue , Imunoglobulina M/sangue , Imunossupressores/uso terapêutico , Neoplasia Residual , Nefelometria e Turbidimetria , Tomografia por Emissão de Pósitrons , Pirazinas/uso terapêutico , Indução de Remissão , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Macroglobulinemia de Waldenstrom/sangue , Macroglobulinemia de Waldenstrom/patologiaRESUMO
The treatment of Condylomata acuminata often causes disappointment to both the physician and the patient since most of the current medical approaches require multiple examines while on the other hand success rates are low and recurrence rates remain high. The treatment approaches include surgical as well as non-surgical methods. The non-surgical treatment includes the application of local agents such as imiquimod, podophyllotoxin, and 5-fluorouracil. Other local agents, used in outpatient treatment settings, include trichloroacetic acid (TCA), podophyllin, or the intralesional application of agents such as interferon and bleomycin. The surgical methods include cryotherapy, electrosurgery, excision and laser therapy. Their major goal is the removal of the visible lesions. The development of the laser systems and the new HPV vaccines are a significant progress in the treatment and prevention of the HPV infections.
Assuntos
Condiloma Acuminado/terapia , Doenças dos Genitais Femininos/terapia , Alphapapillomavirus/isolamento & purificação , Aminoquinolinas/uso terapêutico , Antimetabólitos/uso terapêutico , Cáusticos/uso terapêutico , Condiloma Acuminado/diagnóstico , Condiloma Acuminado/tratamento farmacológico , Condiloma Acuminado/cirurgia , Crioterapia , Eletrocirurgia , Feminino , Fluoruracila/uso terapêutico , Doenças dos Genitais Femininos/diagnóstico , Doenças dos Genitais Femininos/tratamento farmacológico , Doenças dos Genitais Femininos/cirurgia , Humanos , Imiquimode , Indutores de Interferon/uso terapêutico , Podofilina/uso terapêutico , Ácido Tricloroacético/uso terapêuticoAssuntos
Alopurinol/uso terapêutico , Síndrome de Lise Tumoral/tratamento farmacológico , Alopurinol/administração & dosagem , Alopurinol/economia , Antimetabólitos/administração & dosagem , Antimetabólitos/economia , Antimetabólitos/uso terapêutico , Humanos , Hiperpotassemia/etiologia , Hiperpotassemia/metabolismo , Hiperuricemia/etiologia , Infusões Intravenosas , Fosfatos/metabolismo , Fatores de Risco , Urato Oxidase/administração & dosagem , Urato Oxidase/economia , Urato Oxidase/uso terapêuticoRESUMO
Tumor lysis syndrome (TLS) is a serious complication in patients with hematological malignancies. Massive lysis of tumor cells can lead to hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcaemia. These metabolic disturbances may result in renal failure, because of precipitation of uric acid crystals and calcium phosphate salts in the kidney. The standard prophylaxis or treatment of hyperuricemia consists of decreasing uric acid production with allopurinol and facilitating its excretion by urinary alkalinization and hyperhydration. By inhibiting the enzyme xanthine oxidase, allopurinol blocks the conversion of hypoxanthine and xanthine into uric acid. An alternative treatment is urate oxidase which oxidates uric acid into allantoin. Allantoin is 5-10 times more soluble than uric acid and is therefore excreted easily. In several clinical trials rasburicase, the recombinant form of urate oxidase, has shown to be very effective in preventing and treating hyperuricemia. Rasburicase, in contrast with the non-recombinant form of urate oxidase uricozyme, is associated with a low incidence of hypersensitivity reactions. In addition to the demonstrated clinical benefit, rasburicase also proved to be a cost-effective option in the management of hyperuricemia.
Assuntos
Hiperuricemia/tratamento farmacológico , Urato Oxidase/uso terapêutico , Alopurinol/uso terapêutico , Antimetabólitos/uso terapêutico , Ensaios Clínicos como Assunto , Análise Custo-Benefício , Sequestradores de Radicais Livres/farmacologia , Humanos , Hipoxantina/metabolismo , Fatores de Tempo , Síndrome de Lise Tumoral/prevenção & controle , Urato Oxidase/metabolismo , Ácido Úrico/metabolismo , Xantina Oxidase/antagonistas & inibidoresRESUMO
BACKGROUND: Targeting 2-hr postdose cyclosporine (C2) levels to 1,000 to 1,700 mg/dL during the first 6 months after renal transplantation is recommended for triple immunosuppressive regimens. This trial determines whether lower C2 levels could be targeted safely in de novo kidney transplant recipients under a quadruple regimen compared with a similar cohort monitored with trough (C0) levels. METHODS: This single-center, sequential, cohort-designed trial included patients who received Thymoglobulin, corticosteroids, an antimetabolite, and cyclosporine monitored by C2 (n=50) or C0 (n=50). Cyclosporine was tapered to maintain the C2 between 1,000 and 1,200 ng/mL months 0 to 3 and between 600 and 1,000 ng/mL thereafter and C0 between 250 and 350 ng/mL months 0 to 3 and between 100 and 250 ng/mL thereafter. RESULTS: Baseline patient and donor characteristics were similar. There were no differences in graft survival (100% C2 vs. 100% C0), acute rejection (4% C2 vs. 6% C0), allograft function, or adverse events at 6 months. C2 levels were lower than the suggested guidelines throughout the study (33% lower at 1 month and 48% lower at 6 months). Lower cyclosporine doses were achieved in the C2 arm compared with the C0 arm by 1 month and were sustained throughout the trial, which translated into an average cyclosporine cost savings of USD $773 in the C2 arm during the 6-month period (P<0.001). CONCLUSION: With a quadruple immunosuppressive regimen and lower C2 targets than recommended for triple therapy, safe and effective cyclosporine minimization was achieved. Lower cyclosporine doses were achieved in C2-monitored patients compared with C0-monitored patients, translating into lower immunosuppressive costs.
Assuntos
Controle de Custos , Ciclosporina/administração & dosagem , Ciclosporina/sangue , Custos de Medicamentos , Imunossupressores/administração & dosagem , Transplante de Rim , Corticosteroides/economia , Corticosteroides/uso terapêutico , Adulto , Soro Antilinfocitário/economia , Soro Antilinfocitário/uso terapêutico , Antimetabólitos/economia , Antimetabólitos/uso terapêutico , Estudos de Coortes , Ciclosporina/economia , Ciclosporina/uso terapêutico , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/economia , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: We compared the direct medical costs of secondary prophylaxis with bisphosphonates (BPs) in bone metastases (BMs) of breast cancer (BCa) from a payer perspective. PATIENTS AND METHODS: This study adopted an incidence-based chart review of consecutive BCa patients with BMs who received prophylactic treatment with orally administered (po) clodronate (CLODpo group), or intravenously administered (iv) pamidronate (PAM group) in 1997 at two large oncology centers in Toronto, Ontario. We evaluated the difference in costs of management of patients among the CLODpo and PAM groups using an intent-to-treat analysis from diagnosis of BMs to death, or last follow-up. The results are presented as observed mean and average lifetime (including terminal care) costs per patient. RESULTS: The observed mean costs in the PAM and CLODpo groups were 49,472 dollars and 50,307 dollars (2002 Canadian dollars), respectively. The difference in costs between the CLODpo (n=34) and PAM (n=18) groups was not significant (P=0.64), and remained robust after sensitivity analyses. The corresponding average lifetime costs were 65,677 dollars in the CLODpo group and 61,254 dollars in the PAM group. Inpatient and terminal care were the major cost drivers, comprising 45% and 25% of overall costs. Of all hospitalizations, 46% were associated with complications from BMs. CONCLUSIONS: Our analysis, which was based on a convenience sample, failed to reveal a statistically significant difference in the observed mean costs between groups of patients who initiated treatment with po clodronate versus iv pamidronate. The cost estimates from this study can be used for future corroborative economic analyses.
Assuntos
Antimetabólitos/economia , Antineoplásicos/economia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Ácido Clodrônico/economia , Difosfonatos/economia , Antimetabólitos/uso terapêutico , Antineoplásicos/uso terapêutico , Distribuição de Qui-Quadrado , Ácido Clodrônico/uso terapêutico , Análise Custo-Benefício , Difosfonatos/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Pamidronato , Estatísticas não ParamétricasAssuntos
Antineoplásicos/efeitos adversos , Neoplasias/tratamento farmacológico , Síndrome de Lise Tumoral/etiologia , Alopurinol/uso terapêutico , Antimetabólitos/uso terapêutico , Antineoplásicos/uso terapêutico , Análise Custo-Benefício , Inibidores Enzimáticos/uso terapêutico , Humanos , Fatores de Risco , Síndrome de Lise Tumoral/economia , Síndrome de Lise Tumoral/prevenção & controle , Urato Oxidase/economia , Urato Oxidase/uso terapêutico , Ácido Úrico/metabolismo , Equilíbrio HidroeletrolíticoRESUMO
BACKGROUND: In the current economic climate, it is important to justify the cost of treatments used in dermatology, particularly where cheaper alternatives exist. OBJECTIVES: To determine which treatment modality commonly used for Bowen's disease is associated with the lowest cost to the National Health Service. METHODS: A cost-minimization analysis was used to compare the following six treatments for Bowen's disease: cryotherapy, curettage and cautery, excision, laser ablation, photodynamic therapy and 5-fluorouracil. These are all known to have similar recurrence rates. Information regarding use of these treatment modalities was extracted from a literature review. Costs were determined from published data, average wholesale prices of medications, staff salary pay scales and health economics departments. RESULTS: The results show that, if treatment is indeed undertaken, a single lesion of Bowen's disease is most cheaply treated by curettage or excision biopsy under local anaesthetic, and most expensively treated by photodynamic therapy. The usefulness of this information has to be taken in the context of the study design, outcome measurements and base assumptions. CONCLUSIONS: Valid costing studies such as this, in conjunction with evidence of effectiveness and safety, can provide guidance for resource allocation and treatment decisions.
Assuntos
Doença de Bowen/economia , Medicina Estatal/economia , Antimetabólitos/economia , Antimetabólitos/uso terapêutico , Biópsia/economia , Doença de Bowen/terapia , Análise Custo-Benefício , Custos e Análise de Custo , Crioterapia/economia , Curetagem/economia , Fluoruracila/economia , Fluoruracila/uso terapêutico , Humanos , Terapia a Laser/economia , Fotoquimioterapia/economiaRESUMO
PURPOSE: To examine why most ophthalmologists routinely use mitomycin C or 5-fluorouracil (antimetabolites) in association with filtering surgery for glaucoma. METHODS: Critical analysis of seven medical, social and economic trends. RESULTS: The rapid acceptance of the adjunctive use of antimetabolites at the time of filtration surgery may be explained by reasons other than anticipated increase in the "success" of glaucoma surgery. CONCLUSION: The use of antimetabolites in conjuction with filtering glaucoma surgery may be at least partially a consequence of changing medical-social-economic factors, rather than solely a desire on the part of physicians to improve the "success" of glaucoma surgery. This may indicate a need to reevaluate the proper place of antimetabolites in association with filtration surgery.
Assuntos
Antimetabólitos/uso terapêutico , Fluoruracila/uso terapêutico , Glaucoma/tratamento farmacológico , Glaucoma/cirurgia , Mitomicina/uso terapêutico , Trabeculectomia , Terapia Combinada , Atenção à Saúde/economia , Glaucoma/economia , Humanos , Pressão IntraocularAssuntos
Alopurinol/uso terapêutico , Antimetabólitos/uso terapêutico , Síndrome de Lise Tumoral/tratamento farmacológico , Doença Aguda , Alopurinol/administração & dosagem , Alopurinol/economia , Antimetabólitos/administração & dosagem , Antimetabólitos/economia , Análise Custo-Benefício , Humanos , Síndrome de Lise Tumoral/economia , Síndrome de Lise Tumoral/prevenção & controleRESUMO
We evaluated whether trough cyclosporine (CYA) level monitoring was useful in the diagnosis of rejection within 2 weeks after transplantation. Rejection occurred in 14 out of 17 patients (82.3%) treated with CYA, mizoribine (MZR) and prednisolone (Pred) when trough CYA levels dropped below 70 ng/ml, suggesting the importance of trough level monitoring. When anti-lymphocyte globulin (ALG) was added to the 3 above-mentioned drugs, however, rejection occurred in only 1 patient (6.7%) and 2 patients (13.3%), respectively, within 1 week and 1-2 weeks after transplantation, suggesting that trough level monitoring is less important in patients treated with these 4 drugs.