RESUMO
Recurrent copy number variants of the q21.1 region of chromosome 1 have been associated with variable clinical features, including developmental delay, mild to moderate intellectual disability, psychiatric and behavioral problems, congenital heart malformations, and craniofacial abnormalities. A subset of individuals is clinically unaffected. We describe a unique 3-generation family with a large recurrent 1q21.1 microduplication (BP2-BP4). Our observations underline the incomplete penetrance and phenotypic variability of this rearrangement. We also confirm the association with congenital heart malformations, chronic depression, and anxiety. Furthermore, we report a broader range of dysmorphic features. The extreme phenotypic heterogeneity observed in this family suggests that additional factors modify the clinical phenotype.
RESUMO
OBJECTIVE: To assess the balance between costs and upper gastrointestinal (GI) side effects of treatment with celecoxib, nonsteroidal antiinflammatory drugs (NSAIDs) alone, NSAID plus misoprostol, NSAID plus histamine-2 receptor antagonist (H(2)RA), NSAID plus proton pump inhibitor (PPI), and Arthrotec in The Netherlands. METHODS: A model was used to convene data from various sources on the probability of GI side effects and resource use. The probabilities of GI side effects for celecoxib and NSAIDs alone were derived from trial data. Calculations were based on 6 months of treatment, and were from a societal perspective. Distinction was made between low-, medium-, and high-risk patients. An extensive probabilistic sensitivity analysis was performed to address uncertainty. RESULTS: Assuming an average patient, the total costs per 6 months of therapy were: celecoxib 255 Euro, NSAIDs alone 166 Euro, NSAID plus misoprostol 285 Euro, NSAID plus H(2)RA 284 Euro, NSAID plus PPI 243 Euro, and Arthrotec 187 Euro. Treatment with celecoxib was associated with the lowest number of GI side effects and related deaths. Incremental costs per life-year saved for Arthrotec compared to NSAIDs alone were 5676 Euro for all patients and 526 Euro for medium-to-high-risk patients, whereas for high-risk patients, Arthrotec dominated NSAID alone. For celecoxib compared to Arthrotec, the incremental cost-effectiveness ratios (ICERs) were 56,667 Euro, 33,684 Euro, and 15,429 Euro, respectively. CONCLUSION: Assuming a limit of 20,000 Euro per life-year gained, from an economic point of view, Arthrotec is the preferred treatment when all patients or medium-to-high-risk patients are considered. In high-risk patients, celecoxib is the preferred treatment strategy.
Assuntos
Anti-Inflamatórios não Esteroides/economia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/economia , Diclofenaco/economia , Antagonistas dos Receptores H2 da Histamina/economia , Misoprostol/economia , Modelos Econômicos , Osteoartrite/tratamento farmacológico , Osteoartrite/economia , Inibidores da Bomba de Prótons/economia , Pirazóis/economia , Sulfonamidas/economia , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Celecoxib , Ensaios Clínicos como Assunto , Análise Custo-Benefício , Árvores de Decisões , Diclofenaco/efeitos adversos , Diclofenaco/uso terapêutico , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Antagonistas dos Receptores H2 da Histamina/efeitos adversos , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Humanos , Masculino , Misoprostol/efeitos adversos , Misoprostol/uso terapêutico , Países Baixos , Inibidores da Bomba de Prótons/efeitos adversos , Inibidores da Bomba de Prótons/uso terapêutico , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Sulfonamidas/efeitos adversos , Sulfonamidas/uso terapêutico , Resultado do TratamentoRESUMO
Currently, up to 50% of the operations in early-stage non-small cell lung cancer (NSCLC) are futile owing to the presence of locally advanced tumour or distant metastases. More accurate pre-operative staging is required in order to reduce the number of futile operations. The cost-effectiveness of fluorine-18 fluorodeoxyglucose positron emission tomography ((18)FDG-PET) added to the conventional diagnostic work-up was studied in the PLUS study. Prior to invasive staging and/or thoracotomy, 188 patients with (suspected) NSCLC were randomly assigned to conventional work-up (CWU) and whole-body PET or to CWU alone. CWU was based on prevailing guidelines. Pre-operative staging was followed by 1 year of follow-up. Outcomes are expressed in the percentage of correctly staged patients and the associated costs. The cost price of PET varied between
Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/economia , Análise Custo-Benefício/métodos , Fluordesoxiglucose F18/economia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/economia , Tomografia Computadorizada de Emissão/economia , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Estadiamento de Neoplasias/economia , Estadiamento de Neoplasias/métodos , Países Baixos , Compostos Radiofarmacêuticos/economia , Reprodutibilidade dos Testes , Medição de Risco/economia , Medição de Risco/métodos , Sensibilidade e Especificidade , Tomografia Computadorizada de Emissão/métodosRESUMO
BACKGROUND: The presence of (distant) metastases affects the therapy (operation) and prognosis of patients with non-small-cell lung cancer (NSCLC). Fifty percent of the operations are futile due to the presence of a locally advanced tumor or distant metastases. Therefore, more accurate preoperative staging is required with respect to the outcomes (reduction of futile operations) and costs. This study examines current staging procedures and assesses possible situations for incorporating positron emission tomography (PET). METHODS: A retrospective analysis was performed to assess actual clinical practice in the staging procedure of 337 patients with NSCLC in two Dutch hospitals. Consequently, by combining these data of actual clinical practice with a literature review, a model was developed to determine the influence of PET on the staging outcomes and the costs. In this model the accuracy and costs of PET can be varied as well as the extent of substitution of conventional diagnostic tests by PET. RESULTS: Practice variation was found between the two hospitals with regard to the setting in which the diagnostic staging took place (hospitalization, outpatient setting) and the extent of the use of mediastinoscopy. This was reflected in the costs and in the number of (futile) operations. CONCLUSION: Hospitalization is the major cost driver in these patients. From a cost viewpoint, the evaluation of PET in a strategy after diagnostic imaging but prior to invasive staging seems most optimal.