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1.
AJR Am J Roentgenol ; 203(6): W629-36, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25415728

RESUMO

OBJECTIVE: The objective of this study was to quantify the effects of radiation-induced cancer risks in patients with Bosniak category IIF lesions undergoing CT versus MRI surveillance. MATERIALS AND METHODS: We developed a Markov-Monte Carlo model to determine life expectancy losses attributable to radiation-induced cancers in hypothetical patients undergoing CT versus MRI surveillance of Bosniak IIF lesions. Our model tracked hypothetical patients as they underwent imaging surveillance for up to 5 years, accounting for potential lesion progression and treatment. Estimates of radiation-induced cancer mortality were generated using a published organ-specific radiation-risk model based on Biological Effects of Ionizing Radiation VII methods. The model also incorporated surgical mortality and renal cancer-specific mortality. Our primary outcome was life expectancy loss attributable to radiation-induced cancers. A sensitivity analysis was performed to assess the stability of the results with variability in key parameters. RESULTS: The mean number of examinations per patient was 6.3. In the base case, assuming 13 mSv per multiphase CT examination, 64-year-old men experienced an average life expectancy decrease of 5.5 days attributable to radiation-induced cancers from CT; 64-year-old women experienced a corresponding life expectancy loss of 6.9 days. The results were most sensitive to patient age: Life expectancy loss attributable to radiation-induced cancers increased to 21.6 days in 20-year-old women and 20.0 days in 20-year-old men. Varied assumptions of each modality's (CT vs MRI) depiction of lesion complexity also impacted life expectancy losses. CONCLUSION: Microsimulation modeling shows that radiation-induced cancer risks from CT surveillance for Bosniak IIF lesions minimally affect life expectancy. However, as progressively younger patients are considered, increasing radiation risks merit stronger consideration of MRI surveillance.


Assuntos
Doenças Renais Císticas/diagnóstico , Doenças Renais Císticas/mortalidade , Expectativa de Vida , Imageamento por Ressonância Magnética/mortalidade , Modelos Estatísticos , Neoplasias Induzidas por Radiação/mortalidade , Tomografia Computadorizada por Raios X/mortalidade , Comorbidade , Simulação por Computador , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Imageamento por Ressonância Magnética/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Medição de Risco , Vigilância de Evento Sentinela , Análise de Sobrevida , Taxa de Sobrevida , Tomografia Computadorizada por Raios X/estatística & dados numéricos
2.
Ann Intern Med ; 158(12): 853-60, 2013 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-23778902

RESUMO

BACKGROUND: Observation is underutilized among men with localized, low-risk prostate cancer. OBJECTIVE: To assess the costs and benefits of observation versus initial treatment. DESIGN: Decision analysis simulating treatment or observation. DATA SOURCES: Medicare schedules, published literature. TARGET POPULATION: Men aged 65 and 75 years who had newly diagnosed low-risk prostate cancer (prostate-specific antigen level <10 µg/L, stage ≤T2a, Gleason score ≤3 + 3). TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: Treatment (brachytherapy, intensity-modulated radiation therapy, or radical prostatectomy) or observation (active surveillance [AS] or watchful waiting [WW]). OUTCOME MEASURES: Quality-adjusted life expectancy and costs. RESULTS OF BASE-CASE ANALYSIS: Observation was more effective and less costly than initial treatment. Compared with AS, WW provided 2 additional months of quality-adjusted life expectancy (9.02 vs. 8.85 years) at a savings of $15,374 ($24,520 vs. $39,894) in men aged 65 years and 2 additional months (6.14 vs. 5.98 years) at a savings of $11,746 ($18,302 vs. $30,048) in men aged 75 years. Brachytherapy was the most effective and least expensive initial treatment. RESULTS OF SENSITIVITY ANALYSIS: Treatment became more effective than observation when it led to more dramatic reductions in prostate cancer death (hazard ratio, 0.47 vs. WW and 0.64 vs. AS). Active surveillance became as effective as WW in men aged 65 years when the probability of progressing to treatment on AS decreased below 63% or when the quality of life with AS versus WW was 4% higher in men aged 65 years or 1% higher in men aged 75 years. Watchful waiting remained least expensive in all analyses. LIMITATION: Results depend on outcomes reported in the published literature, which is limited. CONCLUSION: Among these men, observation is more effective and costs less than initial treatment, and WW is most effective and least expensive under a wide range of clinical scenarios. PRIMARY FUNDING SOURCE: National Cancer Institute, U.S. Department of Defense, Prostate Cancer Foundation, and Institute for Clinical and Economic Review.


Assuntos
Custos de Cuidados de Saúde , Neoplasias da Próstata/economia , Neoplasias da Próstata/terapia , Conduta Expectante/economia , Idoso , Biópsia/economia , Braquiterapia/economia , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Exame Retal Digital/economia , Progressão da Doença , Humanos , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Antígeno Prostático Específico/sangue , Prostatectomia/economia , Neoplasias da Próstata/mortalidade , Anos de Vida Ajustados por Qualidade de Vida , Fatores de Risco , Sensibilidade e Especificidade
3.
Nucleic Acids Res ; 38(8): 2617-23, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20211841

RESUMO

Synthetic biology projects aim to produce physical DNA that matches a designed target sequence. Chemically synthesized oligomers are generally used as the starting point for building larger and larger sequences. Due to the error rate of chemical synthesis, these oligomers can have many differences from the target sequence. As oligomers are joined together to make larger and larger synthetic intermediates, it becomes essential to perform quality control to eliminate intermediates with errors and retain only those DNA molecules that are error free with respect to the target. This step is often performed by transforming bacteria with synthetic DNA and sequencing colonies until a clone with a perfect sequence is identified. Here we present CloneQC, a lightweight software pipeline available as a free web server and as source code that performs quality control on sequenced clones. Input to the server is a list of desired sequences and forward and reverse reads for each clone. The server generates summary statistics (error rates and success rates target-by-target) and a detailed report of perfect clones. This software will be useful to laboratories conducting in-house DNA synthesis and is available at http://cloneqc.thruhere.net/ and as Berkeley Software Distribution (BSD) licensed source.


Assuntos
Desoxirribonucleotídeos/síntese química , Análise de Sequência de DNA/normas , Software , Sequência de Bases , DNA/química , Desoxirribonucleotídeos/química , Controle de Qualidade
4.
Science ; 344(6179): 55-8, 2014 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-24674868

RESUMO

Rapid advances in DNA synthesis techniques have made it possible to engineer viruses, biochemical pathways and assemble bacterial genomes. Here, we report the synthesis of a functional 272,871-base pair designer eukaryotic chromosome, synIII, which is based on the 316,617-base pair native Saccharomyces cerevisiae chromosome III. Changes to synIII include TAG/TAA stop-codon replacements, deletion of subtelomeric regions, introns, transfer RNAs, transposons, and silent mating loci as well as insertion of loxPsym sites to enable genome scrambling. SynIII is functional in S. cerevisiae. Scrambling of the chromosome in a heterozygous diploid reveals a large increase in a-mater derivatives resulting from loss of the MATα allele on synIII. The complete design and synthesis of synIII establishes S. cerevisiae as the basis for designer eukaryotic genome biology.


Assuntos
Cromossomos Fúngicos , Saccharomyces cerevisiae/genética , Biologia Sintética/métodos , Sequência de Bases , Cromossomos Fúngicos/genética , Cromossomos Fúngicos/metabolismo , DNA Fúngico/genética , Genes Fúngicos , Aptidão Genética , Genoma Fúngico , Instabilidade Genômica , Íntrons , Dados de Sequência Molecular , Mutação , Reação em Cadeia da Polimerase , RNA Fúngico/genética , RNA de Transferência/genética , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/fisiologia , Análise de Sequência de DNA , Deleção de Sequência , Transformação Genética
5.
Med Decis Making ; 33(6): 819-38, 2013 08.
Artigo em Inglês | MEDLINE | ID: mdl-23689044

RESUMO

BACKGROUND: We developed preference-based and summated scale scoring for the Testing Morbidities Index (TMI) classification, which addresses short-term effects on quality of life from diagnostic testing before, during, and after testing procedures. METHODS: The two TMI preference functions use multiattribute value techniques; one is patient-based and the other has a societal perspective, informed by 206 breast biopsy patients and 466 (societal) subjects. Because of a lack of standard short-term methods for this application, we used the visual analog scale (VAS). Waiting tradeoff (WTO) tolls provided an additional option for linear transformation of the TMI. We randomized participants to 1 of 3 surveys: The first derived weights for generic testing morbidity attributes and levels of severity with the VAS; a second developed VAS values and WTO tolls for linear transformation of the TMI to a "dead-healthy" scale; the third addressed initial validation in a specific test (breast biopsy). The initial validation included 188 patients and 425 community subjects. Direct VAS and WTO values were compared with the TMI. Alternative TMI scoring as a nonpreference summated scale was included, given evidence of construct and content validity. RESULTS: The patient model can use an additive function, whereas the societal model is multiplicative. Direct VAS and the VAS-scaled TMI were correlated across modeling groups (r = 0.45-0.62). Agreement was comparable to the value function validation of the Health Utilities Index 2. Mean absolute difference (MAD) calculations showed a range of 0.07-0.10 in patients and 0.11-0.17 in subjects. MAD for direct WTO tolls compared with the WTO-scaled TMI varied closely around 1 quality-adjusted life day. CONCLUSIONS: The TMI shows initial promise in measuring short-term testing-related health states.


Assuntos
Morbidade , Pacientes , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Feminino , Humanos , Psicometria
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