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1.
Am J Gastroenterol ; 115(3): 381-387, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31899705

RESUMO

OBJECTIVES: The risk of noncardia gastric cancer is increased in the presence of gastric intestinal metaplasia. We aimed to identify demographic and lifestyle factors independently associated with the risk of gastric intestinal metaplasia. METHODS: We used data from a cross-sectional study of patients attending primary care and endoscopy clinics at the Michael E. DeBakey VA Medical Center in Houston, Texas, between February 2008 and August 2013. All patients completed standardized questionnaires and underwent endoscopy with gastric mapping biopsies. Gastric intestinal metaplasia cases included patients with intestinal metaplasia on any noncardia gastric biopsy; we defined extensive gastric intestinal metaplasia as antrum and corpus involvement. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariate logistic regression models. RESULTS: We identified 423 cases with gastric intestinal metaplasia and 1,796 controls without gastric intestinal metaplasia. Older age (vs <60 years: 60-69 years AdjOR, 1.50; 95% CI, 1.17-1.93; ≥70 years AdjOR, 2.12; 95% CI, 1.48-3.04), male sex (AdjOR, 2.76; 95% CI, 1.50-5.10), nonwhite race/ethnicity (vs non-Hispanic white: Hispanic, AdjOR, 2.66; 95% CI, 1.89-3.76; black, AdjOR, 2.36; 95% CI, 1.85-3.02), and current smoking status (AdjOR, 1.78; 95% CI, 1.29-2.48) were independently associated with gastric intestinal metaplasia. These risk factors remained statistically significantly associated with gastric intestinal metaplasia after adjusting for Helicobacter pylori infection, and their effect sizes were larger for associations with extensive gastric intestinal metaplasia compared with focal gastric intestinal metaplasia. DISCUSSION: Older age, male sex, nonwhite race/ethnicity, and current smoking status were the nonendoscopic factors independently associated with gastric intestinal metaplasia in a predominantly nonimmigrant US population.


Assuntos
Demografia , Intestinos/patologia , Estilo de Vida , Lesões Pré-Cancerosas/etiologia , Gastropatias/etiologia , Estômago/patologia , Saúde dos Veteranos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/patologia , Estudos Prospectivos , Fatores de Risco , Gastropatias/diagnóstico , Gastropatias/patologia , Texas
3.
Semin Oncol ; 46(4-5): 351-361, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31757478

RESUMO

BACKGROUND: With 1.3 million new cases in 2018 worldwide, prostate cancer remains a challenge. Development of novel therapies targeting the androgen pathway followed recognition of the continued importance of androgens in castrate-resistant prostate cancer. To assess abiraterone and enzalutamide efficacy we analyzed data from US Veterans Administration Medical Centers (VAMCs). METHODS: We used a novel method independent of assessment intervals and ideal for real-world analysis to estimate rates of tumor growth (g) and regression (d). FINDINGS: Using the VA Informatics and Computing Infrastructure, we collected data from 5,116 Veterans with castrate-resistant prostate cancer prescribed abiraterone, enzalutamide or both. We estimated values for g and d and demonstrated a correlation of g with overall survival (P < .0001). Abiraterone and enzalutamide slowed growth rates across age groups and across the entire VAMC system, although less so in Veterans previously treated with a taxane and those with Gleason grade group 5 tumors. Abiraterone and enzalutamide efficacy in first-line were comparable although abiraterone in first-line slowed growth rates significantly more in African Americans than in Caucasians; enzalutamide was a better salvage therapy. When abiraterone was first-line and g was low, switching to enzalutamide was associated with a faster g in 67%. INTERPRETATION: In the real-world g can be estimated using a novel analysis method indifferent to assessment intervals that correlates highly with OS. While we show excellent real-world outcomes with abiraterone and enzalutamide, 2 effective and tolerable therapies, our results in VAMCs suggest enzalutamide should follow abiraterone. Changing therapies may be detrimental and consideration should be given to continue monitoring of growth rates over time. Funding Support from the Prostate Cancer Foundation and the Blavatnik Family Foundation.


Assuntos
Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/terapia , Saúde dos Veteranos , Veteranos , Androstenos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Gerenciamento Clínico , Humanos , Masculino , Feniltioidantoína/administração & dosagem , Feniltioidantoína/análogos & derivados , Neoplasias da Próstata/patologia , Resultado do Tratamento , Estados Unidos/epidemiologia , Saúde dos Veteranos/estatística & dados numéricos
4.
Semin Oncol ; 46(4-5): 346-350, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31699443

RESUMO

Research in the Veterans Health Administration (VHA) has played an integral part in learning about cancer biology and treatment. Here we provide examples of past research performed in the VHA focusing on hematologic malignancies, and identify future opportunities for areas of research in this group of uncommon diseases that have specific importance for Veterans and the VHA. Veterans treated in the VHA and in the private sector deserve information that is focused on them, and is not an extrapolation from the larger population. Only by building upon and expanding existing research within the VHA can Veteran-specific results be collected and best practices be developed. In turn, such advances will benefit Veterans affected by these cancers with an improved quality of life and a longer lifespan.


Assuntos
Pesquisa Biomédica , Neoplasias Hematológicas/epidemiologia , Oncologia , Saúde dos Veteranos , Veteranos , Pesquisa Biomédica/estatística & dados numéricos , Pesquisa Biomédica/tendências , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/terapia , Humanos , Oncologia/métodos , Oncologia/estatística & dados numéricos , Estados Unidos/epidemiologia , Saúde dos Veteranos/estatística & dados numéricos , Saúde dos Veteranos/tendências
5.
Semin Oncol ; 46(4-5): 334-340, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31703932

RESUMO

Cancer is a leading cause of death for people with HIV (PWH). The Veterans Healthcare System (VA) is the largest single institutional provider of HIV care in the United States. Cancer among Veterans with HIV is major issue and clinical research has expanded significantly during the antiretroviral therapy (ART) era providing numerous insights regarding cancer incidence, risk factors, prevention, treatment and outcomes for this unique group of patients. This work has been greatly facilitated by the availability of national VA data sources. Notably, patterns of cancer incidence have changed for Veterans with HIV during the ART era; non-AIDS defining malignancies now are the most common tumors. Despite better HIV control in the ART era, immunosuppression measured by low CD4 counts and HIV viremia have been associated with increased cancer risk. Cancer outcomes for Veterans with HIV may now be similar to uninfected Veterans, but information on outcomes and cancer treatment patterns remains limited, requiring further study to help inform prevention and treatment strategies.


Assuntos
Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Neoplasias/epidemiologia , Neoplasias/etiologia , Saúde dos Veteranos/estatística & dados numéricos , Veteranos , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Incidência , Masculino , Neoplasias/prevenção & controle , Pesquisa , Medição de Risco , Fatores de Risco , Estados Unidos/epidemiologia
6.
Semin Oncol ; 46(4-5): 321-326, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31690464

RESUMO

Lung cancer is one of the most common and difficult to treat cancers. Veterans are disproportionately affected by lung cancer, as approximately 20% of all cancers diagnosed within the Veteran Affairs health system are lung cancers. Many Veterans have extensive comorbidities, and thus they are often excluded from clinical trials based on this and other eligibility criteria. Thus, while clinical trials are the gold standard to guide treatment decisions, many Veterans' clinical situations will not align with clinical trial criteria. The Department of Veterans Affairs has established a Central Cancer Registry to aid in evaluation of cancer outcomes and other studies, and data in the registry date back to 1995. This has provided a rich source of data for outcome-based and other research. Here, we highlight studies that utilized the Veterans Affairs Central Cancer Registry to analyze lung cancer outcomes in Veterans treated within the Veterans Affairs health system.


Assuntos
Neoplasias Pulmonares/epidemiologia , Sistema de Registros , Saúde dos Veteranos/estatística & dados numéricos , Comorbidade , Grupos Étnicos , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Estados Unidos/epidemiologia , Estados Unidos/etnologia
7.
Semin Oncol ; 46(4-5): 327-333, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31708233

RESUMO

BACKGROUND: There is wide interest in developing prognostic models in non-small-cell lung cancer (NSCLC) due to the heterogeneity of the disease. Models developed at other healthcare institutions may not be directly applicable for patients treated at the Department of Veterans Affairs (VA). External validation of a candidate prognostic model among VA patients would be crucial before it can be implemented to aid clinical decision-making. METHODS: A prognostic model for mortality developed in the Military Health System (MHS) was applied to data from the VA Precision Oncology Data Repository (VA-PODR), which is available to researchers inside and outside the VA at the Veterans Precision Oncology Data Commons (VPODC). Measures of discrimination and calibration were calculated for the MHS model. The MHS model was also refitted in VA-PODR data using the same risk factors to compare the effect of specific factors and predictive performance when the model is developed using VA data. RESULTS: Time-dependent AUC of the MHS prognostic model was 0.788, 0.806, 0.780, and 0.779 for predicting survival at 1, 2, 3, and 5 years following diagnosis, respectively. Significant discrepancies were found between predicted and observed rates of survival, particularly for later years. When the model is refit in VA-PODR data, it achieved cross-validated AUCs of 0.739, 0.773, 0.769, and 0.807 at the same time points, and discrepancies between predicted and observed survival were reduced. CONCLUSIONS: Validation of the MHS prognostic model in VA-PODR demonstrates that its discrimination remains strong when applied to VA patients. Nevertheless, further calibration to VA data may be needed to improve its risk estimation performance. This study highlights the utility of VA-PODR and the VPODC as a national resource for developing analytic tools that are well adapted to the Veteran population.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Saúde dos Veteranos/estatística & dados numéricos , Veteranos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Feminino , Seguimentos , Humanos , Masculino , Oncologia , Pessoa de Meia-Idade , Mortalidade , Medicina de Precisão , Prognóstico , Curva ROC , Reprodutibilidade dos Testes , Fatores de Risco , Estados Unidos/epidemiologia
9.
Vasc Health Risk Manag ; 15: 409-418, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571892

RESUMO

Introduction: Previous studies have shown that veterans with lower limb amputation have a higher risk for cardiovascular disease (CVD) compared with population-based controls. American veterans who have served in Iraq and Afghanistan with lower limb amputation may be at a similarly higher risk. Patients and methods: The Navel Health Research Center (NHRC) maintains the Expeditionary Medical Encounter Database (EMED) of military personnel who have sustained combat limb amputation or serious limb injury during the conflicts in Iraq and Afghanistan. Department of Veterans Affairs data from 2003 to April 2015 was used to analyze CVD risk factors in this cohort. Veterans with either unilateral (n=442) or bilateral (n=146) lower limb amputation were compared to those with serious lower limb trauma without amputation (n=184). Multivariate regression was used to measure associations between lower limb amputation and CVD risk factors over an average of 8 years of follow-up. Outcomes included mean arterial pressure (MAP), low-density lipoprotein, high-density lipoprotein (HDL), and serum triglycerides (TG). Results: Compared with the limb injury group, those with unilateral lower limb amputation had significantly lower HDL (p<0.05) and higher TG (p<0.05). Those with bilateral lower limb amputation had significantly higher MAP (p<0.05), lower HDL (p<0.01), and higher TG (p<0.001). The prevalence of metabolic syndrome, defined as type 2 diabetes or a constellation of blood pressure and lipid changes consistent with metabolic syndrome, was 8.7%, 14.9%, and 21.9% for limb injury, unilateral amputation, and bilateral amputation groups, respectively. Veterans with bilateral lower limb amputation had a 2.25-increased odds ratio (95% confidence interval 1.19-5.05) of type 2 diabetes or blood pressure and lipid changes consistent with metabolic syndrome compared to those with limb injury. Conclusions: Results suggest that veterans with lower limb amputation have a higher risk for metabolic syndrome. Primary care interventions to manage weight, blood pressure, and lipid levels are fundamental in order to reduce cardiac risk in this relatively young cohort.


Assuntos
Amputação/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Extremidade Inferior/irrigação sanguínea , Síndrome Metabólica/epidemiologia , Lesões do Sistema Vascular/cirurgia , Saúde dos Veteranos , Adulto , Campanha Afegã de 2001- , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Bases de Dados Factuais , Feminino , Hemodinâmica , Humanos , Guerra do Iraque 2003-2011 , Lipídeos/sangue , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Estados Unidos/epidemiologia , United States Department of Veterans Affairs , Lesões do Sistema Vascular/diagnóstico , Lesões do Sistema Vascular/epidemiologia , Lesões do Sistema Vascular/fisiopatologia
10.
Semin Oncol ; 46(4-5): 314-320, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31629530

RESUMO

The Department of Veterans Affairs (VA) has a strong track record providing high-quality, evidence-based care to cancer patients. In order to accelerate discoveries that will further improve care for Veterans with cancer, the VA has partnered with the Center for Translational Data Science at the University of Chicago and the Open Commons Consortium to establish a data sharing platform, the Veterans Precision Oncology Data Commons (VPODC). The VPODC makes clinical, genomic, and imaging data from the VA available to the research community at large. In this paper, we detail our motivation for data sharing, describe the VPODC, and outline our collaboration model. By transforming VA data into a national resource for research in precision oncology, the VPODC seeks to foster innovation through collaboration and resource sharing that will ultimately lead to improved care for Veterans with cancer.


Assuntos
Bases de Dados Factuais , Oncologia , Medicina de Precisão , Saúde dos Veteranos , Segurança Computacional , Humanos , Oncologia/normas , Medicina de Precisão/métodos , Medicina de Precisão/normas , Saúde dos Veteranos/normas
11.
BMC Health Serv Res ; 19(1): 734, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31640673

RESUMO

BACKGROUND: Veterans who access both the Veterans Health Administration (VA) and non-VA health care systems require effective care coordination to avoid adverse health care outcomes. These dual-use Veterans have diverse and complex needs. Gaps in transitions of care between VA and non-VA systems are common. The Advanced Care Coordination (ACC) quality improvement program aims to address these gaps by implementing a comprehensive longitudinal care coordination intervention with a focus on Veterans' social determinants of health (SDOH) to facilitate Veterans' transitions of care back to the Eastern Colorado Health Care System (ECHCS) for follow-up care. METHODS: The ACC program is an ongoing quality improvement study that will enroll dual-use Veterans after discharge from non-VA emergency department (EDs), and will provide Veterans with social worker-led longitudinal care coordination addressing SDOH and providing linkage to resources. The ACC social worker will complete biopsychosocial assessments to identify Veteran needs, conduct regular in-person and phone visits, and connect Veterans back to their VA care teams. We will identify non-VA EDs in the Denver, Colorado metro area that will provide the most effective partnership based on location and Veteran need. Veterans will be enrolled into the ACC program when they visit one of our selected non-VA EDs without being hospitalized. We will develop a program database to allow for continuous evaluation. Continuing education and outreach including the development of a resource guide, Veteran Care Cards, and program newsletters will generate program buy-in and bridge communication. We will evaluate our program using the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework, supported by the Practical, Robust Implementation and Sustainability Model, Theoretical Domains Framework, and process mapping. DISCUSSION: The ACC program will improve care coordination for dual-use Veterans by implementing social-work led longitudinal care coordination addressing Veterans' SDOH. This intervention will provide an essential service for effective care coordination.


Assuntos
Transferência de Pacientes , Atenção Primária à Saúde/organização & administração , United States Department of Veterans Affairs/organização & administração , Saúde dos Veteranos , Veteranos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Humanos , Transferência de Pacientes/organização & administração , Avaliação de Programas e Projetos de Saúde , Melhoria de Qualidade , Estados Unidos , Veteranos/psicologia
12.
Semin Oncol ; 46(4-5): 341-345, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31606147

RESUMO

Management of hematologic malignancies in older patients is complex and, with recent and anticipated trends in demographics, increasingly common. As a large, nationally integrated medical system the Veterans Affairs has the potential to lead in research to benefit these patients. In this review we describe the evolving treatment paradigms of hematologic malignancies and how they are best fit with older patients through comprehensive evaluation of key vulnerabilities. We also discuss optimization of supportive care and navigation services to target identified risks and challenges aimed at ameliorating the patient's burden of cancer and treatment. Lastly, we discuss opportunities in design of prospective clinical trials to better align with real-world cases, thereby expanding enrollment of and applicability to older patients with hematologic malignancies.


Assuntos
Pesquisa Biomédica , Avaliação Geriátrica , Neoplasias Hematológicas/epidemiologia , Saúde dos Veteranos , Veteranos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Pesquisa Biomédica/estatística & dados numéricos , Ensaios Clínicos como Assunto , Gerenciamento Clínico , Feminino , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/terapia , Humanos , Masculino , Estados Unidos/epidemiologia , Saúde dos Veteranos/estatística & dados numéricos
13.
Med Care ; 57(10): 773-780, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31415338

RESUMO

INTRODUCTION: Colorectal cancer (CRC) is a common but largely preventable malignancy. Screening is recommended for all adults aged 50-75 years; however, screening rates are low nationally and vary by patient factors and across health care systems. It is currently unknown whether there are inequities in CRC screening rates by patient sociodemographic and/or clinical factors in the Veterans Health Administration (VA) where the majority of patients are CRC screening-eligible age and CRC is the third most commonly diagnosed cancer. METHODS: We performed a retrospective cohort study using VA national clinical performance and quality data to determine the overall CRC screening rate, rates by patient sociodemographic and clinical factors, and predictors of screening adjusting for patient and system factors. We also determined whether disparities in screening exist in VA. RESULTS: The overall CRC screening rate in VA was 81.5%. Screening rates were lowest among American Indians/Alaska Natives [75.3%; adjusted odds ratio (aOR)=0.77, 95% confidence interval (CI)=0.65-0.90], those with serious mental illness (75.8%; aOR=0.65, 95% CI=0.61-0.69), those with substance abuse (76.9%; aOR=0.76, 95% CI=0.72-0.80), and those in the lowest socioeconomic status quintile (79.5%; aOR=1.10-1.31 for quintiles 2-5 vs. lowest quintile 1). Increasing age, Hispanic ethnicity, black race, Asian race, and high comorbidity were significant predictors of screening uptake. CONCLUSIONS: Many racial/ethnic disparities in CRC screening documented in non-VA settings do not exist in VA. Nonetheless, overall high VA CRC screening rates have not reached American Indians/Alaska Natives, low socioeconomic status groups, and those with mental illness and substance abuse. These groups might benefit from additional targeted efforts to increase screening uptake.


Assuntos
Colonoscopia/estatística & dados numéricos , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Saúde dos Veteranos/estatística & dados numéricos , Idoso , Neoplasias Colorretais/etnologia , Neoplasias Colorretais/psicologia , Grupos Étnicos/estatística & dados numéricos , Feminino , Disparidades em Assistência à Saúde , Hispano-Americanos/estatística & dados numéricos , Humanos , Índios Norte-Americanos/estatística & dados numéricos , Masculino , Saúde Mental/etnologia , Saúde Mental/estatística & dados numéricos , Pessoa de Meia-Idade , Razão de Chances , Aceitação pelo Paciente de Cuidados de Saúde/etnologia , Pobreza/etnologia , Pobreza/estatística & dados numéricos , Estudos Retrospectivos , Fatores Socioeconômicos , Estados Unidos , United States Department of Veterans Affairs , Saúde dos Veteranos/etnologia
15.
Trials ; 20(1): 435, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307502

RESUMO

BACKGROUND: Some individuals who sustain traumatic brain injuries (TBIs) continue to experience significant cognitive impairments chronically (months to years post injury). Many tests of executive function are insensitive to these executive function impairments, as such impairments may only appear during complex daily life conditions. Daily life often requires us to divide our attention and focus on abstract goals. In the current study, we compare the effects of two 1-month electronic cognitive rehabilitation programs for individuals with chronic TBI. The active program (Expedition: Strategic Advantage) focuses on improving goal-directed executive functions including working memory, planning, long-term memory, and inhibitory control by challenging participants to accomplish life-like cognitive simulations. The challenge level of the simulations increases in accordance with participant achievement. The control intervention (Expedition: Informational Advantage) is identical to the active program; however, the cognitive demand level is capped, preventing participants from advancing beyond a set level. We will evaluate these interventions with a military veteran TBI population. METHODS/DESIGN: One hundred individuals will be enrolled in this double-blinded clinical trial (all participants and testers are blinded to condition). Each individual will be randomly assigned to one of two interventions. The primary anticipated outcomes are improvement of daily life cognitive function skills and daily life functions. These are measured by a daily life performance task, which tests cognitive skills, and a survey that evaluates daily life functions. Secondary outcomes are also predicted to include improvements in working memory, attention, planning, and inhibitory control as measured by a neuropsychological test battery. Lastly, neuroimaging measures will be used to evaluate changes in brain networks supporting cognition pre and post intervention. DISCUSSION: We will test whether electronically delivered cognitive rehabilitation aimed at improving daily life functional skills will provide cognitive and daily life functional improvements for individuals in the chronic phase of TBI recovery (greater than 3 months post injury). We aim to better understand the cognitive processes involved in recovery and the characteristics of individuals most likely to benefit. This study will also address the potential to observe generalizability or to transfer from a software-based cognitive training tool toward daily life improvement. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03704116 . Retrospectively registered on 12 Oct 2018.


Assuntos
Lesões Encefálicas Traumáticas/reabilitação , Encéfalo/fisiopatologia , Cognição , Terapia Cognitivo-Comportamental/métodos , Função Executiva , Jogos de Vídeo , Atividades Cotidianas , Adolescente , Adulto , Atenção , Lesões Encefálicas Traumáticas/diagnóstico , Lesões Encefálicas Traumáticas/fisiopatologia , Lesões Encefálicas Traumáticas/psicologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Memória , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Texas , Fatores de Tempo , Resultado do Tratamento , Saúde dos Veteranos , Adulto Jovem
17.
Int J Radiat Oncol Biol Phys ; 104(5): 1181-1182, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31327418
18.
Nat Neurosci ; 22(9): 1394-1401, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31358989

RESUMO

Post-traumatic stress disorder (PTSD) is a major problem among military veterans and civilians alike, yet its pathophysiology remains poorly understood. We performed a genome-wide association study and bioinformatic analyses, which included 146,660 European Americans and 19,983 African Americans in the US Million Veteran Program, to identify genetic risk factors relevant to intrusive reexperiencing of trauma, which is the most characteristic symptom cluster of PTSD. In European Americans, eight distinct significant regions were identified. Three regions had values of P < 5 × 10-10: CAMKV; chromosome 17 closest to KANSL1, but within a large high linkage disequilibrium region that also includes CRHR1; and TCF4. Associations were enriched with respect to the transcriptomic profiles of striatal medium spiny neurons. No significant associations were observed in the African American cohort of the sample. Results in European Americans were replicated in the UK Biobank data. These results provide new insights into the biology of PTSD in a well-powered genome-wide association study.


Assuntos
Predisposição Genética para Doença/genética , Transtornos de Estresse Pós-Traumáticos/genética , Adulto , Estudos de Coortes , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Estados Unidos , Veteranos , Saúde dos Veteranos
19.
JAMA Netw Open ; 2(6): e195345, 2019 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-31173123

RESUMO

Importance: Implementation of pharmacogenetic testing to guide drug prescribing has potential to improve drug response and prevent adverse events. Robust data exist for more than 30 gene-drug pairs linking genotype to drug response phenotypes; however, it is unclear which pharmacogenetic tests, if implemented, would provide the greatest utility for a given patient population. Objectives: To project the proportion of veterans in the US Veterans Health Administration (VHA) with actionable pharmacogenetic variants and evaluate how testing might be associated with prescribing decisions. Design, Setting, and Participants: This cross-sectional study included veterans who used national VHA pharmacy services from October 1, 2011, to September 30, 2017. Data analyses began April 26, 2018, and were completed February 6, 2019. Exposures: Receipt of level A drugs based on VHA pharmacy dispensing records. Main Outcomes and Measures: Projected prevalence of actionable pharmacogenetic variants among VHA pharmacy users based on variant frequencies from the 1000 Genomes Project and veteran demographic characteristics; incident number of level A prescriptions, and proportion of new level A drug recipients projected to carry an actionable pharmacogenetic variant. Results: During the study, 7 769 359 veterans (mean [SD] age, 58.1 [17.8] years; 7 021 504 [90.4%] men) used VHA pharmacy services. It was projected that 99% of VHA pharmacy users would carry at least 1 actionable pharmacogenetic variant. Among VHA pharmacy users, 4 259 153 (54.8%) received at least 1 level A drug with 1 188 124 (15.3%) receiving 2 drugs, and 912 189 (11.7%) receiving 3 or more drugs. The most common incident prescriptions during the study were tramadol (923 671 new recipients), simvastatin (533 928 new recipients), citalopram (266 952 new recipients), and warfarin (205 177 new recipients). Gene-drug interactions projected to have substantial clinical impacts in the VHA population include the interaction of SLCO1B1 with simvastatin (1 988 956 veterans [25.6%]), CYP2D6 with tramadol (318 544 veterans [4.1%]), and CYP2C9 or VKORC1 with warfarin (7 163 349 veterans [92.2%]). Conclusions and Relevance: Clinically important pharmacogenetic variants are highly prevalent in the VHA population. Almost all veterans would carry an actionable variant, and more than half of the population had been exposed to a drug affected by these variants. These results suggest that pharmacogenetic testing has the potential to affect pharmacotherapy decisions for commonly prescribed outpatient medications for many veterans.


Assuntos
Frequência do Gene/genética , Variantes Farmacogenômicos/genética , Medicamentos sob Prescrição/uso terapêutico , Saúde dos Veteranos , Estudos Transversais , Citocromo P-450 CYP2C9/genética , Citocromo P-450 CYP2D6/genética , Interações Medicamentosas/genética , Utilização de Instalações e Serviços , Feminino , Genótipo , Humanos , Transportador 1 de Ânion Orgânico Específico do Fígado/genética , Masculino , Pessoa de Meia-Idade , Assistência Farmacêutica/estatística & dados numéricos , Polimorfismo Genético/genética , Prevalência , Sinvastatina/farmacologia , Tramadol/farmacologia , Estados Unidos , United States Department of Veterans Affairs/estatística & dados numéricos , Vitamina K Epóxido Redutases/genética , Varfarina/farmacologia
20.
BMJ ; 365: l1580, 2019 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-31147311

RESUMO

OBJECTIVE: To estimate all cause mortality and cause specific mortality among patients taking proton pump inhibitors (PPIs). DESIGN: Longitudinal observational cohort study. SETTING: US Department of Veterans Affairs. PARTICIPANTS: New users of PPIs (n=157 625) or H2 blockers (n=56 842). MAIN OUTCOME MEASURES: All cause mortality and cause specific mortality associated with taking PPIs (values reported as number of attributable deaths per 1000 patients taking PPIs). RESULTS: There were 45.20 excess deaths (95% confidence interval 28.20 to 61.40) per 1000 patients taking PPIs. Circulatory system diseases (number of attributable deaths per 1000 patients taking PPIs 17.47, 95% confidence interval 5.47 to 28.80), neoplasms (12.94, 1.24 to 24.28), infectious and parasitic diseases (4.20, 1.57 to 7.02), and genitourinary system diseases (6.25, 3.22 to 9.24) were associated with taking PPIs. There was a graded relation between cumulative duration of PPI exposure and the risk of all cause mortality and death due to circulatory system diseases, neoplasms, and genitourinary system diseases. Analyses of subcauses of death suggested that taking PPIs was associated with an excess mortality due to cardiovascular disease (15.48, 5.02 to 25.19) and chronic kidney disease (4.19, 1.56 to 6.58). Among patients without documented indication for acid suppression drugs (n=116 377), taking PPIs was associated with an excess mortality due to cardiovascular disease (22.91, 11.89 to 33.57), chronic kidney disease (4.74, 1.53 to 8.05), and upper gastrointestinal cancer (3.12, 0.91 to 5.44). Formal interaction analyses suggested that the risk of death due to these subcauses was not modified by a history of cardiovascular disease, chronic kidney disease, or upper gastrointestinal cancer. Taking PPIs was not associated with an excess burden of transportation related mortality and death due to peptic ulcer disease (as negative outcome controls). CONCLUSIONS: Taking PPIs is associated with a small excess of cause specific mortality including death due to cardiovascular disease, chronic kidney disease, and upper gastrointestinal cancer. The burden was also observed in patients without an indication for PPI use. Heightened vigilance in the use of PPI may be warranted.


Assuntos
Doenças Cardiovasculares/mortalidade , Neoplasias Gastrointestinais/mortalidade , Úlcera Péptica/prevenção & controle , Inibidores da Bomba de Prótons/uso terapêutico , Insuficiência Renal Crônica/mortalidade , Saúde dos Veteranos/estatística & dados numéricos , Idoso , Causas de Morte , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mortalidade , Fatores de Risco , Estados Unidos/epidemiologia
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