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1.
BMC Cancer ; 21(1): 785, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34233640

RESUMO

BACKGROUND: Irreversible electroporation (IRE) is a local ablation technique utilizing high voltage, low energy direct current to create nanopores in cell membrane which disrupt homeostasis and leads to cell death. Previous reports have suggested IRE may have a role in treating borderline resectable and unresectable Stage 3 pancreatic tumors. METHODS: Patients with Stage 3 pancreatic ductal adenocarcinoma (PDAC) will be enrolled in either a randomized, controlled, multicenter trial (RCT) or a multicenter registry study. Subjects enrolled in the RCT must have no evidence of disease progression after 3 months of modified FOLFIRINOX (mFOLFIRINOX) treatment prior to being randomization to either a control or IRE arm. Post-induction and post-IRE treatment for the control and IRE arms, respectively, will be left to the discretion of the treating physician. The RCT will enroll 528 subjects with 264 per arm and include up to 15 sites. All subjects will be followed for at least 24 months or until death. The registry study will include two cohorts of patients with Stage 3 PDAC, patients who received institutional standard of care (SOC) alone and those treated with IRE in addition to SOC. Both cohorts will be required to have undergone at least 3 months of SOC without progression prior to enrollment. The registry study will enroll 532 patients with 266 patients in each arm. All patients will be followed for at least 24 months or until death. The primary efficacy endpoint for both studies will be overall survival (OS). Co-primary safety endpoints will be 1) time from randomization or enrollment in the registry to death or new onset of Grade 4 adverse event (AE), and (2 high-grade complications defined as any AE or serious AE (SAE) with a CTCAE v5.0 grade of 3 or higher. Secondary endpoints will include progression-free survival, cancer-related pain, quality of life, and procedure-related pain for the IRE arm only. DISCUSSION: These studies are intended to provide Level 1 clinical evidence and real-world data demonstrating the clinical utility and safety of the use of IRE in combination with chemotherapy in patients with Stage 3 PDAC. TRIAL REGISTRATION: Clinicaltrials.gov NCT03899636 and NCT03899649. Registered April 2, 2019. Food and Drug Administration (FDA) Investigational Device Exemption (IDE) trial G180278 approved on May 3, 2019.


Assuntos
Técnicas de Ablação/métodos , Adenocarcinoma/cirurgia , Neoplasias Pancreáticas/cirurgia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Humanos , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Sistema de Registros , Análise de Sobrevida , Resultado do Tratamento
2.
Respiration ; 99(2): 108-118, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31982886

RESUMO

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a life-threatening interstitial lung disease (ILD). Characterizing health outcomes of IPF patients is challenging due to disease rarity. OBJECTIVE: This study aimed to identify the burden of disease in patients newly diagnosed with IPF. METHODS: Patients with ≥1 claim with an IPF diagnosis were identified from a United States healthcare insurer's database (2000-2013). Patients with other known causes of ILD or aged <40 years were excluded. Subgroups were compared based on the 2011 change in International Classification of Diseases, 9th Revision (ICD-9) definition of IPF and occurrence of IPF testing. The prevalence and incidence of preselected health conditions of clinical interest were estimated. RESULTS: Median age of newly diagnosed patients (n = 7,298) was 62 years (54.0% male). Restricting to patients with IPF diagnostic testing did not substantially affect cohort characteristics, nor did ICD-9 IPF coding change. Mean follow-up was 1.7 years; 16.8% of patients died; and a substantial proportion of patients were censored due to end of health plan enrollment (50.7%) and other causes of ILD (19.6%). The incidence of pulmonary hypertension, lung cancer, and claims-based algorithm proxy for acute respiratory worsening of unknown cause was 22.5, 17.6, and 12.6 per 1,000 person-years, respectively. CONCLUSIONS: Patients with IPF had a high disease burden with a variety of health outcomes observed, including a high rate of mortality. Database censoring due to changes in enrollment or other ILD diagnoses limited follow-up. Altering cohort entry definitions, including IPF testing or ICD-9 IPF coding change, had little impact on cohort baseline characteristics.


Assuntos
Glucocorticoides/uso terapêutico , Custos de Cuidados de Saúde , Hospitalização/estatística & dados numéricos , Fibrose Pulmonar Idiopática/terapia , Oxigenoterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes , Lavagem Broncoalveolar , Estudos de Coortes , Bases de Dados Factuais , Progressão da Doença , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Humanos , Fibrose Pulmonar Idiopática/economia , Fibrose Pulmonar Idiopática/epidemiologia , Incidência , Neoplasias Pulmonares/epidemiologia , Transplante de Pulmão , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Avaliação de Resultados em Cuidados de Saúde , Inibidores da Agregação Plaquetária , Prevalência , Inibidores da Bomba de Prótons/uso terapêutico , Hipertensão Arterial Pulmonar/epidemiologia , Estados Unidos/epidemiologia
3.
Artigo em Inglês | MEDLINE | ID: mdl-25709706

RESUMO

BACKGROUND: Risk evaluation and mitigation strategies (REMS), as mandated by the US Food and Drug Administration (FDA) for medications with the potential for harm, are increasingly incorporating rigid protocols for patient evaluation, but little is known about compliance with these programs. Despite the inherent limitations, data on administrative claims may provide an opportunity to investigate adherence to these programs. METHODS: We assessed adherence to liver function test (LFT) requirements included in the REMS program for bosentan through use of administrative claims. Patients observed in the Optum Research Database who were initiators of bosentan from November 20, 2001 to March 31, 2013 were included. Adherence to LFTs was calculated using pharmacy claims for bosentan dispensation and medical claims for laboratory services, and was assessed at the time of drug initiation and within specified time intervals throughout follow-up. RESULTS: Of 742 patients, 523 (70.5%) had ≥1 qualifying LFT. Among patients with ≥12 dispensations, claims for LFTs at individual dispensations were 53.2-64.0%. Median proportion of dispensations with ≥1 LFT was 0.8 among patients with ≥6 (interquartile range, 0.7-1.0) or ≥12 (0.7-0.9) dispensations. Adherence was 90-100% for 33.3% of all initiators, whereas 29.3% of initiators were non-adherent (defined as <50% of on-therapy LFTs). CONCLUSIONS: Analyses of administrative claims suggest that the REMS program for bosentan may not have adequately guaranteed adherence to the program's monthly monitoring of LFTs. Such investigations of existing REMS programs may provide insight on how to accomplish more successful evaluation of REMS.

4.
J Expo Sci Environ Epidemiol ; 25(6): 567-73, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25182844

RESUMO

Health effects of ambient air pollution are most frequently expressed in individual studies as responses to a standardized unit of air pollution changes (e.g., an interquartile interval), which is thought to enable comparison of findings across studies. However, this approach does not necessarily convey health effects in terms of a real-world air pollution scenario. In the present study, we use population intervention modeling to estimate the effect of an air pollution intervention that makes explicit reference to the observed exposure data and is identifiable in those data. We calculate the association between ambient summertime nitrogen dioxide (NO2) and forced expiratory flow between 25% and 75% of forced vital capacity (FEF25-75) in a cohort of children with asthma in Fresno, California. We scale the effect size to reflect NO2 abatement on a majority of summer days. The effect estimates were small, imprecise, and consistently indicated improved pulmonary function with decreased NO2. The effects ranged from -0.8% of mean FEF25-75 (95% confidence interval (CI): -3.4, 1.7) to -3.3% (95% CI: -7.5, 0.9). We conclude by discussing the nature and feasibility of the exposure change analyzed here given the observed air pollution profile, and we propose additional applications of population intervention models in environmental epidemiology.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Asma/induzido quimicamente , Dióxido de Nitrogênio/efeitos adversos , Poluentes Atmosféricos/análise , California , Criança , Feminino , Fluxo Expiratório Forçado/efeitos dos fármacos , Humanos , Exposição por Inalação/efeitos adversos , Exposição por Inalação/análise , Estudos Longitudinais , Masculino , Modelos Estatísticos , Dióxido de Nitrogênio/análise , Estudos Prospectivos , Capacidade Vital/efeitos dos fármacos
5.
Ann Epidemiol ; 24(12): 888-95e4, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25453347

RESUMO

PURPOSE: To evaluate associations between traffic-related air pollution during pregnancy and preterm birth in births in four counties in California during years 2000 to 2006. METHODS: We used logistic regression to examine the association between the highest quartile of ambient air pollutants (carbon monoxide, nitrogen dioxide, particulate matter <10 and 2.5 µm) and traffic density during pregnancy and each of five levels of prematurity based on gestational age at birth (20-23, 24-27, 28-31, 32-33, and 34-36 weeks) versus term (37-42 weeks). We examined trimester averages and the last month and the last 6 weeks of pregnancy. Models were adjusted for birthweight, maternal age, race/ethnicity, education, prenatal care, and birth costs payment. Neighborhood socioeconomic status (SES) was evaluated as a potential effect modifier. RESULTS: There were increased odds ratios (ORs) for early preterm birth for those exposed to the highest quartile of each pollutant during the second trimester and the end of pregnancy (adjusted OR, 1.4-2.8). Associations were stronger among mothers living in low SES neighborhoods (adjusted OR, 2.1-4.3). We observed exposure-response associations for multiple pollutant exposures and early preterm birth. Inverse associations during the first trimester were observed. CONCLUSIONS: The results confirm associations between traffic-related air pollution and prematurity, particularly among very early preterm births and low SES neighborhoods.


Assuntos
Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/induzido quimicamente , Emissões de Veículos/toxicidade , Adulto , Poluentes Atmosféricos/análise , Peso ao Nascer/efeitos dos fármacos , California/epidemiologia , Monóxido de Carbono/análise , Monóxido de Carbono/toxicidade , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Modelos Logísticos , Masculino , Idade Materna , Exposição Materna , Óxidos de Nitrogênio/análise , Óxidos de Nitrogênio/toxicidade , Material Particulado/análise , Material Particulado/toxicidade , Gravidez , Nascimento Prematuro/epidemiologia , Características de Residência , Medição de Risco , Emissões de Veículos/análise , Adulto Jovem
6.
Am J Epidemiol ; 173(7): 731-8, 2011 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-21415029

RESUMO

The growing body of work in the epidemiology literature focused on G-computation includes theoretical explanations of the method but very few simulations or examples of application. The small number of G-computation analyses in the epidemiology literature relative to other causal inference approaches may be partially due to a lack of didactic explanations of the method targeted toward an epidemiology audience. The authors provide a step-by-step demonstration of G-computation that is intended to familiarize the reader with this procedure. The authors simulate a data set and then demonstrate both G-computation and traditional regression to draw connections and illustrate contrasts between their implementation and interpretation relative to the truth of the simulation protocol. A marginal structural model is used for effect estimation in the G-computation example. The authors conclude by answering a series of questions to emphasize the key characteristics of causal inference techniques and the G-computation procedure in particular.


Assuntos
Causalidade , Projetos de Pesquisa Epidemiológica , Modelos Estatísticos , Simulação por Computador , Fatores de Confusão Epidemiológicos , Humanos , Análise de Regressão
8.
Environ Health Perspect ; 118(10): 1497-502, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20570778

RESUMO

BACKGROUND: Although studies have demonstrated that air pollution is associated with exacerbation of asthma symptoms in children with asthma, little is known about the susceptibility of subgroups, particularly those with atopy. OBJECTIVE: This study was designed to evaluate our a priori hypothesis that identifiable subgroups of asthmatic children are more likely to wheeze with exposure to ambient air pollution. METHODS: A cohort of 315 children with asthma, 6-11 years of age, was recruited for longitudinal follow-up in Fresno, California (USA). During the baseline visit, children were administered a respiratory symptom questionnaire and allergen skin-prick test. Three times a year, participants completed 14-day panels during which they answered symptom questions twice daily. Ambient air quality data from a central monitoring station were used to assign exposures to the following pollutants: particulate matter ≤ 2.5 µm in aerodynamic diameter, particulate matter between 2.5 and 10 µm in aerodynamic diameter (PM10-2.5), elemental carbon, nitrogen dioxide (NO2), nitrate, and O3. RESULTS: For the group as a whole, wheeze was significantly associated with short-term exposures to NO2 [odds ratio (OR) = 1.10 for 8.7-ppb increase; 95% confidence interval (CI), 1.02-1.20] and PM10-2.5 (OR = 1.11 for 14.7-µg/m3 increase; 95% CI, 1.01-1.22). The association with wheeze was stronger for these two pollutants in children who were skin-test positive to cat or common fungi and in boys with mild intermittent asthma. CONCLUSION: A pollutant associated with traffic emissions, NO2, and a pollutant with bioactive constituents, PM10-2.5, were associated with increased risk of wheeze in asthmatic children living in Fresno, California. Children with atopy to cat or common fungi and boys with mild intermittent asthma were the subgroups for which we observed the largest associations.


Assuntos
Poluentes Atmosféricos/toxicidade , Asma/fisiopatologia , Sons Respiratórios/etiologia , Asma/complicações , California , Criança , Humanos , Inquéritos e Questionários
9.
Int J Environ Health Res ; 19(2): 139-55, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19370464

RESUMO

Cross-sectional analyses were conducted to evaluate the effects of exposure to highway traffic on pulmonary function in Fresno, California. Traffic and spirometry data were available for 214 children (enrollment ages six to 11 years). Multiple linear regression was used to evaluate the relations between pulmonary function and traffic parameters. Heavy-duty vehicle count was used as a surrogate measure for diesel-related exposures. Pulmonary function was non-significantly associated with longer distance-to-road and non-significantly associated with higher traffic intensity. Evaluation of effect modification by FEF(25-75)/FVC (a measure of intrinsic airway size) showed that all pulmonary function measures of flow were significantly inversely related to a traffic metric that incorporates traffic intensity and roadway proximity. The results indicate that residence proximity to highway traffic is associated with lower pulmonary function among children with asthma, and smaller airway size is an important modifier of the effect of traffic exposure on pulmonary function and a marker of increased susceptibility.


Assuntos
Asma/fisiopatologia , Exposição Ambiental , Pulmão/fisiopatologia , Emissões de Veículos/toxicidade , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Análise de Regressão , Características de Residência , Testes de Função Respiratória
10.
Pediatr Allergy Immunol ; 16(8): 669-78, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16343089

RESUMO

This study addressed the comparability of data obtained from a student-based and parent-based asthma and respiratory health survey. Our goal was to ascertain whether there were meaningful and systematic differences in asthma classification based on symptom and diagnosis reports obtained separately from students and their parents. A brief, written survey, based on the International Study of Asthma and Allergy in Children questionnaire, was administered to 6th through 10th grade students in two schools in Oakland, CA, USA. Students who reported asthma-like indicators for the previous 12-month period were defined as positive and a more extensive questionnaire was mailed home to those parents. A more refined classification of asthma based on parent report of indicators was compared with student report. Forty-four percent of 1298 students were classified as positive for current asthma-like symptoms and 50% of parent surveys were returned. For the positive students with parent surveys, 59% were classified as 'probable' for asthma based on the parent survey. Overall, the agreement between parent and students' classification was 70%, and 83% for students with a parent report of physician diagnosis of asthma. Students who were discordant with parents for physician diagnosis of asthma were more likely to be male, and more likely to have a parent report of unscheduled Emergency Department visit for wheezing or trouble breathing. Findings indicated that with the exception of medication, students reported asthma indicators more frequently that parents, independent of classification. Student report of physician diagnosis with a 12-month report of an asthma symptom was determined to be a good indicator of probable current asthma. Inclusion of or reliance on a parental questionnaire is not likely to improve the reliability of a school-based asthma surveillance program in our population.


Assuntos
Asma/diagnóstico , Asma/epidemiologia , Inquéritos Epidemiológicos , Pais , Vigilância da População , Estudantes , Adolescente , Adulto , Asma/fisiopatologia , Criança , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Inquéritos e Questionários
11.
Am J Epidemiol ; 162(4): 382-8, 2005 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-16014771

RESUMO

Marginal structural models (MSMs) are being used more frequently to obtain causal effect estimates in observational studies. Although the principal estimator of MSM coefficients has been the inverse probability of treatment weight (IPTW) estimator, there are few published examples that illustrate how to apply IPTW or discuss the impact of model selection on effect estimates. The authors applied IPTW estimation of an MSM to observational data from the Fresno Asthmatic Children's Environment Study (2000-2002) to evaluate the effect of asthma rescue medication use on pulmonary function and compared their results with those obtained through traditional regression methods. Akaike's Information Criterion and cross-validation methods were used to fit the MSM. In this paper, the influence of model selection and evaluation of key assumptions such as the experimental treatment assignment assumption are discussed in detail. Traditional analyses suggested that medication use was not associated with an improvement in pulmonary function--a finding that is counterintuitive and probably due to confounding by symptoms and asthma severity. The final MSM estimated that medication use was causally related to a 7% improvement in pulmonary function. The authors present examples that should encourage investigators who use IPTW estimation to undertake and discuss the impact of model-fitting procedures to justify the choice of the final weights.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Asma/etiologia , Métodos Epidemiológicos , Modelos Estatísticos , Pico do Fluxo Expiratório/efeitos dos fármacos , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , California/epidemiologia , Criança , Humanos , Sons Respiratórios/etiologia
12.
Chest ; 123(6): 1899-907, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12796166

RESUMO

STUDY OBJECTIVES: Laboratory-based spirometry is the "gold standard" for the assessment of lung function, both in clinical and research protocols. These spirometers, however, are neither practical nor affordable for home-based monitoring or studies that collect data in multiple locations. Traditionally, peak flowmeters have been used, but they have important limitations. DESIGN: Based on data from a cohort of 92 children with asthma, we evaluated the agreement between a portable spirometer and a office-based spirometer, using an in-line technique to evaluate measures from the same effort. We compared a range of pulmonary function parameters collected during office-based tests, and also evaluated whether adequate adherence and data quality could be achieved in a home-based study of children with asthma. RESULTS: The agreement between the devices for the actual values of peak expiratory flow, FEV(1), and forced expiratory flow at 25% of FVC was excellent. The portable device was programmed with customized software to grade each curve using revised American Thoracic Society acceptability and reproducibility criteria. For 74% of the curves, quality grade agreed with a grade assigned by physician review of the curve from the office-based spirometer. During 2 weeks of twice-daily monitoring at home, children completed an average of 23 of 28 possible sessions (83%). Of these, 84% had at least two acceptable and two reproducible curves. Although children >or= 8 years old were not more adherent, they were significantly more likely to achieve acceptable and reproducible curves. CONCLUSIONS: Portable spirometers can provide measurements that are highly comparable to those obtained from "gold standard" laboratory spirometers, and high-quality tracings can be achieved both at home and in the office setting. Visual inspection of the curves by experienced reviewers identified unacceptable curves that were not rejected by the quality control software. Portable spirometers are an important contribution to epidemiologic and clinical studies that require frequent measures of a more broad range of pulmonary function parameters than can be provided by peak flowmeters.


Assuntos
Asma/fisiopatologia , Espirometria/instrumentação , Criança , Fluxo Expiratório Forçado , Serviços de Assistência Domiciliar , Humanos , Pico do Fluxo Expiratório
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