RESUMO
METHODS: We conducted a multinational pharmacoeconomic evaluation comparing the immediate release form of a new class of serotonin norepinephrine reuptake inhibitor (SNRI), venlafaxine IR to the selective serotonin reuptake inhibitors (SSRIs) and the tricyclic antidepressants (TCAs) in the treatment of acute major depressive disorder (MDD) in 10 countries (Germany, Italy, Netherlands, Poland, Spain, Sweden, Switzerland, United Kingdom, United States, and Venezuela). We designed a decision analytic model assessing the acute phase of MDD treatment within a 6-month time horizon. Six decision tree models were customized with country-specific estimates from a clinical management analysis, meta-analytic rates from two published meta-analyses, and a resource valuation of treatment costs representing the inpatient and outpatient settings within each country. The meta-analyses provided the clinical rates of success defined as a 50% reduction in depression scores on the Hamilton Depression Scale (HAM-D) or the Montgomery-Asberg Depression Rating Scale (MADRS). Treatment regimen costs were determined from standard lists, fee schedules, and communication with local health economists in each country. The meta-analytic rates were applied to the decision analytic model to calculate the expected cost and expected outcomes for each antidepressant comparator. Cost-effectiveness was determined using the expected values for both a successful outcome, and a composite measure of outcome termed symptom-free days. A policy analysis was conducted to examine the health system budget impact in each country of increasing the utilization of the most effective antidepressant found in our study. RESULTS: Initiating treatment of MDD with venlafaxine IR yielded a lower expected cost compared to the SSRIs and TCAs in all countries except Poland in the inpatient setting, and Italy and Poland within the outpatient settings. The weighted average expected cost per patient varied from US$632 (Poland) to US$5647 (US) in the six-month acute phase treatment of MDD. The estimated total budgetary impact for each 1% of venlafaxine utilization, assuming a population of one million MDD patients, ranged from US$1600 (Italy) to US$29,049 (US). CONCLUSIONS: Within the inpatient and outpatient treatment settings, venlafaxine IR was a more cost-effective treatment of MDD compared to the SSRIs and TCAs. Additionally, the results of this investigation indicate that increased utilization of venlafaxine in most settings across Europe and the Americas will have favorable impact on health care payer budgets. ADR, adverse drug reaction; CMA, clinical management analysis; ECT, electroconvulsive therapy; HAM-D, Hamilton Depression Scale; MADRS, Montgomery-Asberg depression rating scale; MDD, major depressive disorder; SFD, symptom-free day; SNRI, serotonin-norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant; WHO, world health organization.
Assuntos
Antidepressivos de Segunda Geração/economia , Antidepressivos Tricíclicos/economia , Cicloexanóis/economia , Transtorno Depressivo Maior/tratamento farmacológico , Farmacoeconomia/estatística & dados numéricos , Inibidores Seletivos de Recaptação de Serotonina/economia , Antidepressivos de Segunda Geração/uso terapêutico , Antidepressivos Tricíclicos/uso terapêutico , Orçamentos , Análise Custo-Benefício , Cicloexanóis/uso terapêutico , Árvores de Decisões , Transtorno Depressivo Maior/economia , Custos de Medicamentos/estatística & dados numéricos , Europa (Continente) , Pesquisa sobre Serviços de Saúde/métodos , Humanos , Reembolso de Seguro de Saúde , Método de Monte Carlo , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Estados Unidos , Venezuela , Cloridrato de VenlafaxinaRESUMO
We investigated the effect of dexamethasone on parenteral lipid tolerance in 7-day-old extremely low birth weight infants (n = 28) in a randomized, double-blind trial. Serum triglycerides were measured before and after 3 days of dexamethasone or placebo treatment. Infants treated with dexamethasone responded with higher triglyceride concentrations and greater sensitivity to incremental increases in the intravenous lipid dose.
Assuntos
Dexametasona/uso terapêutico , Emulsões Gordurosas Intravenosas/uso terapêutico , Glucocorticoides/uso terapêutico , Recém-Nascido de muito Baixo Peso , Dexametasona/administração & dosagem , Método Duplo-Cego , Glucocorticoides/administração & dosagem , Humanos , Recém-Nascido , Nutrição Parenteral , Estudos Prospectivos , Triglicerídeos/sangueRESUMO
The treatment of colorectal cancer continues to pose major challenges for oncologists throughout the world. Uracil and tegafur (UFT), as an oral agent, represents a new patient-focused approach to managing a malignancy with few treatment alternatives other than an intravenous fluorouracil (5-FU)-based regimen. The ability of UFT to achieve equivalent clinical outcomes compared with continuous 5-FU infusion, along with its oral formulation and mild toxicity profile, provide a compelling backdrop for fiscal analysis. An economic assessment of therapy attributes and effects would, therefore, be prudent and necessary when deliberating the adoption of this chemotherapy regimen. We developed a pharmacoeconomic model in Brazil and Argentina identifying clinical practices associated with chemotherapy administration and adverse event management practices from a panel of physicians assembled in each country. Practice patterns and clinical events were then evaluated for resource utilisation trends. The perspective of this pharmacoeconomic analysis was that of the healthcare payor. Country-specific charge data were applied to the identified resources to arrive at an average cost per patient receiving a 6-cycle course of 5-FU with either levamisole and/or leucovorin as a modulator vs a modelled oral UFT/leucovorin regimen. As a comparator, the oral UFT/leucovorin regimen was modelled based on the expert panel's input. Adverse events and incidence data were derived from clinical trial data for both agents. Both agents were analysed in the treatment of metastatic disease and as adjuvant therapy. The principal findings of a cost-minimisation analysis in Brazil revealed approximately equivalent treatment costs for both regimens in the adjuvant setting. When analysing the metastatic treatment arm, costs diverged by $R335/per patient ($R = Reals - the currency of Brazil) in favour of a UFT regimen. The profile in Argentina yielded more dramatic differences, with a UFT regimen costing $P782/per patient ($P = Pesos - the currency of Argentina) less than a 5-FU regimen in the adjuvant setting. In the treatment of metastatic disease, a UFT regimen provided $P1188/per patient in savings over a 5-FU regimen. These differences are predominantly driven by the mild toxicity profile of UFT and its corresponding less severe adverse event management practice patterns. In addition, the oral formulation of UFT versus intravenous 5-FU provides for ease of administration, lowering the total cost of care as well as likely impacting on the patient's quality of life. The pharmacoeconomic results suggest that a UFT regimen is a useful and economical alternative to the standard 5-FU regimen in the treatment of colorectal cancer in Brazil and Argentina.
RESUMO
OBJECTIVE: We tested the hypothesis that vitamin C supplementation of premature neonates is associated with hemolysis. STUDY DESIGN: A double-blind, randomized, controlled trial of vitamin C supplementation (50 mg/day) was undertaken in premature neonates (birth weight, 1000 to 1500 gm). Infants were randomly assigned to receive vitamin C (Ce-Vi-Sol) (n = 32) or placebo (n = 24) for 14 days. Twenty-three subjects per group were required to detect a difference of 1 SD in corrected carboxyhemoglobin values (alpha = 0.05, beta = 0.10). RESULTS: Day 14 vitamin C levels were lower in control subjects than in supplemented neonates (62 +/- 24 vs 125 +/- 62 micromol/L, p = 0.005). There was no difference in corrected blood carboxyhemoglogin concentrations (0.72 +/- 0.44 vs 0.72 +/- 0.23%; p = 0.95), other parameters of hemolysis, weight gain, blood sampled, presumed septic episodes, necrotizing enterocolitis, feeding intolerance, or transfusion. On day 14, bilirubin values were higher in control subjects than in the supplemented group (77 +/- 37 vs 55 +/- 33 micromol/L; p = 0.04). When a distant outlier in the nonsupplemented group was excluded (163 micromol/L), statistical significance was lost (73 +/- 32 vs 55 +/- 33 micromol/L; p = 0.09). CONCLUSION: Oral supplementation of premature infants with vitamin C is not associated with evidence of increased erythrocyte destruction, hyperbilirubinemia, or other morbidity.
Assuntos
Ácido Ascórbico/efeitos adversos , Hemólise/efeitos dos fármacos , Recém-Nascido Prematuro/fisiologia , Anemia Hemolítica/induzido quimicamente , Ácido Ascórbico/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Hiperbilirrubinemia/induzido quimicamente , Recém-Nascido , Doenças do Prematuro/induzido quimicamente , MasculinoRESUMO
OBJECTIVE: To examine the effectiveness of cyclic oral high-dose (HD) dexamethasone therapy in pediatric patients with chronic immune thrombocytopenic purpura (ITP), which has been reported to cause complete remission in adults with chronic ITP. STUDY DESIGN: Eleven children with primary chronic ITP, with a median disease duration of 28 months (range, 6 to 120 months), were treated with cycles of HD dexamethasone therapy. RESULTS: Excellent short-term responses (initial platelet counts < or = 50 x 10(9)/L, increasing to > 100 x 10(9)/L within 72 hours of completion of an HD dexamethasone cycle) were observed in 78% of 41 cycles. Long-term effects include one complete response (platelet count > or = 150 x 10(9)/L) and three partial responses (platelet count > or = 50 and < 150 x 10(9)/L) in 11 children followed for 6 or more months after completing cyclic HD dexamethasone therapy. Because side effects were substantial, three children did not complete their sixth treatment cycle. At day 6 of treatment, B lymphocytes were significantly increased (p = 0.005). CONCLUSIONS: Dexamethasone, given orally in high doses, is an effective drug in achieving short-term platelet responses, but it induced long-term remissions in fewer than half of the children with well-established chronic ITP. Its effect on B lymphocytes requires further elucidation. A prospective, controlled study will be needed to establish whether cyclic HD dexamethasone therapy can alter the natural history of children with early chronic ITP and thus avoid splenectomy.
Assuntos
Dexametasona/administração & dosagem , Glucocorticoides/administração & dosagem , Púrpura Trombocitopênica/tratamento farmacológico , Administração Oral , Adolescente , Plaquetas/imunologia , Criança , Pré-Escolar , Doença Crônica , Dexametasona/efeitos adversos , Esquema de Medicação , Feminino , Glucocorticoides/efeitos adversos , Humanos , Imunoglobulinas/sangue , Contagem de Leucócitos/efeitos dos fármacos , Masculino , Contagem de Plaquetas/efeitos dos fármacos , Púrpura Trombocitopênica/sangue , Púrpura Trombocitopênica/imunologia , Indução de RemissãoRESUMO
The escalating role played by managed care organizations in the health-care system is reflected in the increased demand for cost-effectiveness analyses (CEAs) to assess the balance between economic impact and clinical efficacy. For example, the high incidence and costs associated with colorectal cancer in Latin America calls for a comprehensive economic evaluation to ensure appropriate allocation of limited health-care funds. In addition, the current call for a "societal" perspective of such analyses indicates the need for increased consideration of the concerns of both patient and health-care provider. The introduction of oral tegafur and uracil (UFT) provided the opportunity to evaluate the pharmacoeconomic advantage of the new agent compared with the standard fluorouracil (5-FU). Results of this study indicated an economic advantage for oral UFT vs a 5-FU-based regimen in the treatment of colorectal cancer in Brazil and Argentina. It was further noted that the mild toxicity profile of UFT reduced both the number of clinic visits and the need for venipuncture procedures. Noting that oral UFT may have a positive impact on quality of life in addition to its estimated economic benefit, it was concluded that prospective economic research and quality-of-life evaluations are needed to fully assess the pharmacoeconomic impact of oral UFT.
Assuntos
Neoplasias Colorretais/economia , Tegafur/economia , Uracila/economia , Argentina , Brasil , Quimioterapia Adjuvante/economia , Neoplasias Colorretais/tratamento farmacológico , Custos e Análise de Custo , Combinação de Medicamentos , Custos de Medicamentos , Fluoruracila/administração & dosagem , Fluoruracila/economia , Humanos , Método de Monte Carlo , América do Sul , Tegafur/uso terapêutico , Uracila/uso terapêuticoRESUMO
To assess dose requirements of warfarin in children, we analyzed retrospectively the treatment of 26 patients with the drug. Subsequently we treated 15 children, prospectively, with a regimen derived from our retrospective analysis (0.2 mg/kg/day for 2 days). In the retrospective analysis we found the prothrombin time (PT) at day 2 to correlate significantly with the dose given on day 0 (p less than 0.001) and with the cumulative dose on days 0 and 1 (p less than 0.001), but the standardized loading regimen resulted in a wide range of PTs independent of age, weight, or body surface area. The warfarin dose contributes only 40% of the variability in PT; an individual child's response to warfarin cannot be predicted accurately on the basis of the usual morphometric measurements.
Assuntos
Próteses Valvulares Cardíacas , Complicações Pós-Operatórias/prevenção & controle , Trombose/prevenção & controle , Varfarina/administração & dosagem , Criança , Relação Dose-Resposta a Droga , Humanos , Testes de Função Hepática , Estudos Prospectivos , Tempo de Protrombina , Estudos RetrospectivosRESUMO
Four patients with classic recalcitrant prurigo nodularis had symptomatic and physical responses to thalidomide with remissions. Three of the four patients had increased IgE levels that decreased during therapy. In two patients, short-term treatment (2 to 3 months) was not sufficient to produce remission, but retreatment was effective. Two patients had long-term remission with more than 6 months of treatment. No significant side effects occurred.