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1.
Int J Audiol ; 63(3): 207-212, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36662150

RESUMO

OBJECTIVE: This exploratory study examined whether central auditory tests show differences between people living with HIV (PLWH) treated with two predominant antiretroviral drug therapy (ART) regimens. DESIGN: Cross-sectional. STUDY SAMPLE: 253 PLWH (mean age 39.8 years) from the Shanghai Public Health Clinical Centre, China. METHODS: The Hearing in Noise Test speech reception threshold (SRT) assessed central auditory function and the Montreal Cognitive Assessment (MoCA) assessed cognition. The relationship between ART regimen and SRT was evaluated with multivariable linear regression incorporating age, HIV duration, and peripheral hearing ability. Multivariable logistic regression was used to ascertain if SRT and ART regimen predicted MoCA impairment. RESULTS: The two predominant ART regimens differed by one drug (zidovudine or tenofovir). Participants taking the zidovudine-containing regimen had poorer SRT performance (p=.012) independent of age and hearing thresholds. MoCA scores did not differ between drug regimens, but a negative relationship was found between SRT and MoCA impairment (p=.048). CONCLUSIONS: ART regimens differed in their association with central auditory test performance likely reflecting neurocognitive changes in PLWH taking the zidovudine-containing regimen. Central auditory test performance also marginally predicted cognitive impairment, supporting further assessment of central auditory tests to detect neurocognitive deficits in PLWH.


Assuntos
Infecções por HIV , Percepção da Fala , Adulto , Humanos , Zidovudina/uso terapêutico , Estudos Transversais , China , Testes Auditivos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia
2.
Int J Mol Sci ; 25(3)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38338815

RESUMO

MicroRNAs (miRNA) in extracellular vesicles and particles (EVPs) in maternal circulation during pregnancy and in human milk postpartum are hypothesized to facilitate maternal-offspring communication via epigenetic regulation. However, factors influencing maternal EVP miRNA profiles during these two critical developmental windows remain largely unknown. In a pilot study of 54 mother-child dyads in the New Hampshire Birth Cohort Study, we profiled 798 EVP miRNAs, using the NanoString nCounter platform, in paired maternal second-trimester plasma and mature (6-week) milk samples. In adjusted models, total EVP miRNA counts were lower for plasma samples collected in the afternoon compared with the morning (p = 0.024). Infant age at sample collection was inversely associated with total miRNA counts in human milk EVPs (p = 0.040). Milk EVP miRNA counts were also lower among participants who were multiparous after delivery (p = 0.047), had a pre-pregnancy BMI > 25 kg/m2 (p = 0.037), or delivered their baby via cesarean section (p = 0.021). In post hoc analyses, we also identified 22 specific EVP miRNA that were lower among participants who delivered their baby via cesarean section (Q < 0.05). Target genes of delivery mode-associated miRNAs were over-represented in pathways related to satiety signaling in infants (e.g., CCKR signaling) and mammary gland development and lactation (e.g., FGF signaling, EGF receptor signaling). In conclusion, we identified several key factors that may influence maternal EVP miRNA composition during two critical developmental windows, which should be considered in future studies investigating EVP miRNA roles in maternal and child health.


Assuntos
Vesículas Extracelulares , MicroRNAs , Lactente , Humanos , Gravidez , Feminino , MicroRNAs/metabolismo , Leite Humano/metabolismo , Cesárea , Estudos de Coortes , Epigênese Genética , Projetos Piloto , Período Pós-Parto , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo
3.
Genet Epidemiol ; 46(7): 347-371, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35842778

RESUMO

The inclusion of ancestrally diverse participants in genetic studies can lead to new discoveries and is important to ensure equitable health care benefit from research advances. Here, members of the Ethical, Legal, Social, Implications (ELSI) committee of the International Genetic Epidemiology Society (IGES) offer perspectives on methods and analysis tools for the conduct of inclusive genetic epidemiology research, with a focus on admixed and ancestrally diverse populations in support of reproducible research practices. We emphasize the importance of distinguishing socially defined population categorizations from genetic ancestry in the design, analysis, reporting, and interpretation of genetic epidemiology research findings. Finally, we discuss the current state of genomic resources used in genetic association studies, functional interpretation, and clinical and public health translation of genomic findings with respect to diverse populations.


Assuntos
Genética Populacional , Genômica , Estudos Epidemiológicos , Estudos de Associação Genética , Humanos , Epidemiologia Molecular
4.
Biostatistics ; 23(3): 926-948, 2022 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-33720330

RESUMO

In light of the low signal-to-noise nature of many large biological data sets, we propose a novel method to learn the structure of association networks using Gaussian graphical models combined with prior knowledge. Our strategy includes two parts. In the first part, we propose a model selection criterion called structural Bayesian information criterion, in which the prior structure is modeled and incorporated into Bayesian information criterion. It is shown that the popular extended Bayesian information criterion is a special case of structural Bayesian information criterion. In the second part, we propose a two-step algorithm to construct the candidate model pool. The algorithm is data-driven and the prior structure is embedded into the candidate model automatically. Theoretical investigation shows that under some mild conditions structural Bayesian information criterion is a consistent model selection criterion for high-dimensional Gaussian graphical model. Simulation studies validate the superiority of the proposed algorithm over the existing ones and show the robustness to the model misspecification. Application to relative concentration data from infant feces collected from subjects enrolled in a large molecular epidemiological cohort study validates that metabolic pathway involvement is a statistically significant factor for the conditional dependence between metabolites. Furthermore, new relationships among metabolites are discovered which can not be identified by the conventional methods of pathway analysis. Some of them have been widely recognized in biological literature.


Assuntos
Algoritmos , Perfilação da Expressão Gênica , Teorema de Bayes , Estudos de Coortes , Perfilação da Expressão Gênica/métodos , Humanos , Distribuição Normal
5.
Pediatr Res ; 93(3): 725-731, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35717483

RESUMO

BACKGROUND: The establishment of the gut microbiome plays a key symbiotic role in the developing immune system; however, its influence on vaccine response is yet uncertain. We prospectively investigated the composition and diversity of the early-life gut microbiome in relation to infant antibody response to two routinely administered vaccines. METHODS: Eighty-three infants enrolled in the New Hampshire Birth Cohort Study were included in the analysis. We collected blood samples at 12 months of age and assayed the isolated serum to quantify total IgG and measured antibody to pneumococcal capsular polysaccharide and tetanus toxoid. Stool samples were collected from infants at 6 weeks of age and sequenced using 16S rRNA, and a subset of 61 samples were sequenced using shotgun metagenomics sequencing. RESULTS: We observed differences in beta diversity for 16S 6-week stool microbiota and pneumococcal and tetanus IgG antibody responses. Metagenomics analyses identified species and metabolic pathways in 6-week stool associated with tetanus antibody response, in particular, negative associations with the relative abundance of Aeriscardovia aeriphila species and positive associations with the relative abundance of species associated with CDP-diacylglycerol biosynthesis pathways. CONCLUSIONS: The early gut microbiome composition may influence an infant's vaccine response. IMPACT: Early intestinal microbiome acquisition plays a critical role in immune maturation and in both adaptive and innate immune response in infancy. We identified associations between early life microbiome composition and response to two routinely administered vaccines-pneumococcal capsular polysaccharide and tetanus toxoid-measured at approximately 1 year of age. Our findings highlight the potential impact of the gut microbiome on infant immune response that may open up opportunities for future interventions.


Assuntos
Microbioma Gastrointestinal , Tétano , Humanos , Lactente , Microbioma Gastrointestinal/genética , Estudos Prospectivos , Estudos de Coortes , RNA Ribossômico 16S/genética , Toxoide Tetânico , Fezes , Imunoglobulina G , Polissacarídeos
6.
Am J Epidemiol ; 191(9): 1614-1625, 2022 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-35689641

RESUMO

We recently conducted an exploratory study that indicated that several direct-acting antivirals (DAAs), highly effective medications for hepatitis C virus (HCV) infection, were also associated with improvement in posttraumatic stress disorder (PTSD) among a national cohort of US Department of Veterans Affairs (VA) patients treated between October 1, 1999, and September 30, 2019. Limiting the same cohort to patients with PTSD and HCV, we compared the associations of individual DAAs with PTSD symptom improvement using propensity score weighting. After identifying patients who had available baseline and endpoint PTSD symptom data as measured with the PTSD Checklist (PCL), we compared changes over the 8-12 weeks of DAA treatment. The DAAs most prescribed in conjunction with PCL measurement were glecaprevir/pibrentasvir (GLE/PIB; n = 54), sofosbuvir/velpatasvir (SOF/VEL; n = 54), and ledipasvir/sofosbuvir (LDV/SOF; n = 145). GLE/PIB was superior to LDV/SOF, with a mean difference in improvement of 7.3 points on the PCL (95% confidence interval (CI): 1.1, 13.6). The mean differences in improvement on the PCL were smaller between GLE/PIB and SOF/VEL (3.0, 95% CI: -6.3, 12.2) and between SOF/VEL and LDV/SOF (4.4, 95% CI: -2.4, 11.2). While almost all patients were cured of HCV (92.5%) regardless of the agent received, PTSD outcomes were superior for those receiving GLE/PIB compared with those receiving LDV/SOF, indicating that GLE/PIB may merit further investigation as a potential PTSD treatment.


Assuntos
Hepatite C Crônica , Hepatite C , Transtornos de Estresse Pós-Traumáticos , Veteranos , Antivirais/uso terapêutico , Quimioterapia Combinada , Genótipo , Hepacivirus/genética , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Humanos , Sofosbuvir/uso terapêutico , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Resposta Viral Sustentada , Resultado do Tratamento
7.
Int J Audiol ; 61(3): 187-196, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34107827

RESUMO

OBJECTIVE: Sampling distortion product otoacoustic emissions (DPOAEs) at multiple f2/f1 ratios and f2 frequency values produces a DPOAE "map." This study examined the efficacy of DPOAE mapping compared with pure tone audiometry and standard DPOAEs for detecting noise effects in subjects exposed to loud sound. DESIGN: A map significance score was developed as a single measure of map change. Significance scores were evaluated before and after exposure to: loud music (LM), controlled noise (CN), and firing range noise (FR) in three separate sets of subjects. Scores were compared to audiometry and standard DPOAE results in the LM study. STUDY SAMPLE: The LM and CN exposure studies involved 22, and 20 healthy young subjects respectively with normal hearing. Eight Marines were studied before and after FR exposure. RESULTS: After LM exposure, audiometry showed significant changes at 1, 2, 4, and 6 kHz. Standard DPOAE measures were also significantly different at several frequencies. Map significance scores detected changes more effectively and showed the distribution of DPOAE alterations. CONCLUSIONS: Map significance scores detected changes after noise exposure more reliably than audiometry and standard DPOAEs. Additionally, maps showed a diffuse response to sound exposure perhaps explaining why individual DP-grams appear less sensitive.


Assuntos
Música , Emissões Otoacústicas Espontâneas , Audiometria de Tons Puros/métodos , Limiar Auditivo/fisiologia , Humanos , Ruído/efeitos adversos , Emissões Otoacústicas Espontâneas/fisiologia
8.
Genomics ; 113(4): 2276-2289, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33965547

RESUMO

BACKGROUND/AIM: There has been increasing evidence for the function of long non-coding RNA (lncRNA) in nasopharyngeal carcinoma (NPC). We aim to delve into the position of lncRNA HOX antisense intergenic RNA (HOTAIR), together with enhancer of zeste homolog 2 (EZH2), E-cadherin and trimethylation of lysine 27 on histone H3 (H3K27me3) in NPC. METHODS: HOTAIR, EZH2, and E-cadherin expression in NPC tissues and cells were tested. NPC cell biological functions were examined through gain-of and loss-of function assays. The mechanism of lncRNA HOTAIR/E-cadherin/EZH2/H3K27 axis in NPC was decoded. RESULTS: LncRNA HOTAIR and EZH2 were highly expressed in NPC, and E-cadherin was lowly expressed. Down-regulation of HOTAIR or EZH2 inhibited NPC cell progression and tumor growth. HOTAIR recruited histone methylase EZH2 to mediate trimethylation of H3K27 and regulated E-cadherin expression. CONCLUSION: HOTAIR inhibits E-cadherin by stimulating the trimethylation of H3K27 to promote NPC cell progression through recruiting histone methylase EZH2.


Assuntos
Neoplasias Nasofaríngeas , RNA Longo não Codificante , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Regulação Neoplásica da Expressão Gênica , Histona Metiltransferases/genética , Histona Metiltransferases/metabolismo , Humanos , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
9.
J Dual Diagn ; 18(4): 185-198, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36151743

RESUMO

OBJECTIVE: To investigate whether direct-acting antivirals (DAA) for hepatitis C viral infection (HCV): glecaprevir/pibrentasvir (GLE/PIB), ledipasvir/sofosbuvir (LDV/SOF), and sofosbuvir/velpatasvir (SOF/VEL) are associated with reduced alcohol consumption among veterans with alcohol use disorder (AUD) and co-occurring post-traumatic stress disorder (PTSD). METHODS: We measured change in Alcohol Use Disorder Identification Test-Consumption Module (AUDIT-C) scores in a retrospective cohort of veterans with PTSD and AUD receiving DAAs for HCV. RESULTS: One thousand two hundred and eleven patients were included (GLE/PIB n = 174, LDV/SOF n = 808, SOF/VEL n = 229). Adjusted frequencies of clinically meaningful improvement were 30.5% for GLE/PIB, 45.5% for LDV/SOF, and 40.5% for SOF/VEL. The frequency was lower for GLE/PIB than for LDV/SOF (OR = 0.59; 95% CI [0.40, 0.87]) or SOF/VEL (OR = 0.66; 95% CI [0.42, 1.04]). CONCLUSIONS: DAA treatment for HCV was associated with a substantial reduction in alcohol use in patients with AUD and co-occurring PTSD. Further exploration of the role of DAAs in AUD treatment is warranted.


Assuntos
Alcoolismo , Hepatite C Crônica , Hepatite C , Transtornos de Estresse Pós-Traumáticos , Humanos , Sofosbuvir/efeitos adversos , Antivirais/uso terapêutico , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Estudos Retrospectivos , Alcoolismo/complicações , Alcoolismo/tratamento farmacológico , Alcoolismo/epidemiologia , Hepacivirus , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Consumo de Bebidas Alcoólicas , Resultado do Tratamento
10.
J Cell Mol Med ; 25(7): 3548-3559, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33728802

RESUMO

Growth arrest-specific 5 (GAS5) is a kind of long non-coding RNAs (lncRNAs). Previous studies showed that down-regulation of LncRNA-GAS5 was involved in the development of systemic lupus erythematosus (SLE). However, the regulatory mechanism of down-expressed LncRNA-GAS5 in SLE remains obscure. In this study, we aimed to investigate the association of LncRNA-GAS5 polymorphism with SLE risk. And further explore how LncRNA-GAS5 is involved in the occurrence of SLE. Here, we evaluated the relationship between the risk for the development of SLE and the 5-base pair (AGGCA/-) insertion/deletion (I/D) polymorphism (rs145204276) in the LncRNA-GAS5 promoter region. A custom 36-Plex SNPscan kit was used for genotyping the LncRNA-GAS5 polymorphisms. The LncRNA-GAS5 and miR-21 target prediction was performed using bioinformatics software. Enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR (qRT-PCR) were performed to assess GAS5 and miR-21 mRNA expression and PTEN protein expression. The results revealed that rs145204276 resulted in a decreased risk of SLE (DD genotypes vs II genotypes: adjusted OR = 0.538, 95% CI, 0.30-0.97, P = .039; ID genotypes vs II genotypes: adjusted OR = 0.641, 95% CI, 0.46-0.89, P = .007; ID/DD genotypes vs II genotypes: adjusted OR = 0.621, 95% CI, 0.46-0.84, P = .002; D alleles vs I alleles: adjusted OR = 0.680, 95% CI, 0.53-0.87, P = .002). A reduced incidence of renal disorders in SLE was found to be related to ID/DD genotypes and D alleles (ID/DD genotypes vs II genotypes: OR = 0.57, 95% CI, 0.36-0.92, P = .020; D alleles vs I alleles: OR = 0.63, 95% CI, 0.43-0.93, P = .019). However, no significant association of rs2235095, rs6790, rs2067079 and rs1951625 polymorphisms with SLE risk was observed (P > .05). Additionally, haplotype analysis showed that a decreased SLE risk resulted from the A-A-C-G-D haplotype (OR = 0.67, 95% CI, 0.49-0.91, P = .010). Also, patients in the SLE group showed a down-regulated expression of LncRNA-GAS5 and PTEN than the healthy volunteers; however, patients with rs145204276 ID/DD genotypes showed up-regulated expression of LncRNA-GAS5 and PTEN compared with patients carrying the II genotype. Furthermore, the miR-21 levels were considerably up-regulated in the SLE group than the healthy volunteers, and patients with rs145204276 ID/DD genotype had lower miR-21 levels than the ones with the II genotype. Thus, we found that the LncRNA-GAS5/miR-21/PTEN signalling pathway was involved in the development of SLE, where LncRNA-GAS5 acted as an miR-21 target, and miR-21 regulated the expression of PTEN. These findings indicated that the rs145204276 ID/DD genotypes in the LncRNA-GAS5 gene promoter region may be protected against SLE by up-regulating the expression of LncRNA-GAS5, which consecutively regulated miR-21 and PTEN levels.


Assuntos
Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/metabolismo , MicroRNAs/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Adulto , Povo Asiático , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Transdução de Sinais
11.
Psychol Med ; 51(8): 1382-1391, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32063248

RESUMO

BACKGROUND: This study evaluated whether natural language processing (NLP) of psychotherapy note text provides additional accuracy over and above currently used suicide prediction models. METHODS: We used a cohort of Veterans Health Administration (VHA) users diagnosed with post-traumatic stress disorder (PTSD) between 2004-2013. Using a case-control design, cases (those that died by suicide during the year following diagnosis) were matched to controls (those that remained alive). After selecting conditional matches based on having shared mental health providers, we chose controls using a 5:1 nearest-neighbor propensity match based on the VHA's structured Electronic Medical Records (EMR)-based suicide prediction model. For cases, psychotherapist notes were collected from diagnosis until death. For controls, psychotherapist notes were collected from diagnosis until matched case's date of death. After ensuring similar numbers of notes, the final sample included 246 cases and 986 controls. Notes were analyzed using Sentiment Analysis and Cognition Engine, a Python-based NLP package. The output was evaluated using machine-learning algorithms. The area under the curve (AUC) was calculated to determine models' predictive accuracy. RESULTS: NLP derived variables offered small but significant predictive improvement (AUC = 0.58) for patients that had longer treatment duration. A small sample size limited predictive accuracy. CONCLUSIONS: Study identifies a novel method for measuring suicide risk over time and potentially categorizing patient subgroups with distinct risk sensitivities. Findings suggest leveraging NLP derived variables from psychotherapy notes offers an additional predictive value over and above the VHA's state-of-the-art structured EMR-based suicide prediction model. Replication with a larger non-PTSD specific sample is required.


Assuntos
Processamento de Linguagem Natural , Prevenção do Suicídio , Humanos , Saúde Mental , Registros Eletrônicos de Saúde , Aprendizado de Máquina , Algoritmos
12.
Neuroepidemiology ; 55(3): 196-205, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33902051

RESUMO

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal, neuromuscular disease with no cure. ALS incidence rates have not been assessed specifically in Ohio, yet the state contains both metropolitan and rural areas with a variety of environmental factors that could contribute to disease etiology. We report the incidence of ALS in Ohio residents diagnosed from October 2016 through September 2018. METHODS: We engaged practitioners from 9 Ohio sites to identify newly diagnosed ALS patients and to complete case report forms with demographic and clinical information. ALS was diagnosed according to the Awaji criteria and classified as either definite, probable, or possible. We developed a method to estimate missing cases using a Poisson regression model to impute cases in counties with evidence of undercounting. RESULTS: We identified 333 newly diagnosed ALS patients residing in Ohio during the 2-year index period and found incidence rates varied in the 88 state counties. After incorporating the estimated 27% of missing cases, the corrected crude annual incidence was 1.96/100,000 person-years, and the age- and gender-standardized incidence was 1.71/100,000 person-years (standardized to the 2010 US census). DISCUSSION/CONCLUSION: The estimated Ohio incidence of ALS is overall similar to that reported in other states in the USA. This study reveals a geospatial variation in incidence within the state, and areas with higher rates warrant future investigation.


Assuntos
Esclerose Lateral Amiotrófica , Esclerose Lateral Amiotrófica/epidemiologia , Humanos , Incidência , Ohio/epidemiologia , Sistema de Registros , Projetos de Pesquisa
13.
Muscle Nerve ; 63(1): 52-59, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33006184

RESUMO

Most amyotrophic lateral sclerosis (ALS) cases are considered sporadic, without a known genetic basis, and environmental exposures are thought to play a causal role. To learn more about sporadic ALS etiology, we recruited n = 188 ALS patients from northern New England and Ohio and matched controls 2:1 from the general population of the same regions. Questionnaires evaluated the association between a variety of lifestyle, behavioral (ie, hobbies and activities), and occupational factors and the risk of ALS, including the duration of time between exposure and ALS onset, and exposure frequency. Head trauma was associated with increased ALS risk (adjusted odds ratio [OR] 1.60 95% confidence interval [CI] 1.04-2.45), with significantly greater effects for injuries occurring 10 or more years prior to symptom onset (P = .037). ALS risk was increased for those reporting severe electrical burns (adjusted OR 2.86, 95% CI 1.37-6.03), with odds ratios highest for burns after age 30 (OR 3.14), and for burns 10 or more years prior to symptom onset (OR 3.09). Hobbies involving lead were the most strongly associated with ALS risk (adjusted OR 2.92, 95% CI 1.45-5.91). Exposures to lead 20 or more years prior to diagnosis had larger effect sizes compared to those occurring more recently. Holding a job in mechanics, painting, or construction was associated with ALS. The identification of these specific environmental factors associated with ALS highlight the need for future prospective and laboratory studies to assess causality, biological mechanisms, and find prevention or treatment opportunities.


Assuntos
Esclerose Lateral Amiotrófica/diagnóstico , Esclerose Lateral Amiotrófica/epidemiologia , Exposição Ambiental , Exposição Ocupacional , Adulto , Idoso , Idoso de 80 Anos ou mais , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Estilo de Vida , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Fatores de Risco , Estados Unidos
14.
J Behav Med ; 44(4): 492-506, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-32915350

RESUMO

There is an elevated risk of suicide among people living in rural areas, and the rural-urban disparity in death by suicide is growing in the general United States population. The department of Veterans Affairs (VA) implemented programs targeting rural health in 2007 and suicide prevention in 2008. Rural-urban differences in suicide rates among VA users have not been examined since 2010. We sought to understand whether the rural-urban disparity in suicide risk among VA users decreased during a time of contemporaneous VA efforts to improve access to mental health care for rural Veterans and to improve the effectiveness of mental health services at preventing suicide. We performed a retrospective cohort study examining differences in the raw and adjusted annual suicide rate among rural and urban VA users between 2003 and 2017. All VHA users 2003-2017. Descriptive statistics are presented for all VHA users in 2017. This includes 6,120,355 unique VA users, 32.0% (n = 1,955,935) of whom lived at a rural address. Raw rates of death by suicide were higher in rural VA users than urban VA users overall (33.3 vs. 29.1 deaths per 100,000 population) and across years, but the age, sex, and race-adjusted rates converged in 2005. White VA users had over triple the rate of death by suicide as black VA users, and lived disproportionally in rural areas. The rural-urban suicide disparity among VA users persists. However, the disparity appears to be driven by differences in the racial composition of rural and urban patients, which were not accounted for in prior studies.


Assuntos
Prevenção do Suicídio , Veteranos , Atenção à Saúde , Humanos , Estudos Retrospectivos , População Rural , Estados Unidos/epidemiologia , United States Department of Veterans Affairs , População Urbana
15.
Adm Policy Ment Health ; 48(1): 70-87, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32394096

RESUMO

We sought to develop a quality standard for the prescription of antidepressants for posttraumatic stress disorder (PTSD) that is both consistent with the underlying evidence supporting antidepressants as a treatment for PTSD and associated with the best levels of symptom improvement. We quantified antidepressant initiation during the first year of PTSD treatment in a 10-year national cohort of Department of Veterans Affairs (VA) users, and compared outcomes in a subgroup who completed patient-reported outcome measurement (PROM) as part of routine practice. We added progressively stringent measurement requirements. Prescribing quality for PTSD in the VA was stable over time. Use of PROM was rare in the case of antidepressant treatment, limiting our assessment of outcomes.


Assuntos
Transtornos de Estresse Pós-Traumáticos , Veteranos , Antidepressivos/uso terapêutico , Humanos , Medidas de Resultados Relatados pelo Paciente , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Estados Unidos , United States Department of Veterans Affairs
16.
Breast Cancer Res Treat ; 183(2): 403-410, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32656723

RESUMO

PURPOSE: Little is known about the three-dimensional shape of breast cancer. Implicit to approaches that localize the center of the tumor for breast-conserving surgery (BCS) of non-palpable cancers is the assumption that breast cancers are spherical about a central point, which may not be accurate. METHODS: Pre-operative supine breast MRI images were obtained of 83 breast cancer patients undergoing partial mastectomy using supine MRI-guided resection techniques. Three-dimensional (3D) tumor models were derived after radiologists outlined tumor edges on successive MRI slices. Ideal resection volumes were determined by adding 1 cm in every dimension to the actual tumor volume. Geometrically defined parameters were used to define tumor shapes and associations between clinical variables and shapes were examined. RESULTS: Seventy-five patients had invasive cancer. Breast cancers were categorized into four tumor shapes: 34% of tumors were discoidal, 29% segmental, 19% spherical, and 18% irregular. If hypothetical spherical excisions were performed, non-spherical cases would excise 143% more tissue than the ideal resection volume. When the 3D shape of each tumor was provided to the surgeon during MR-guided BCS, the percentage of tissue overexcised in non-spherical cases was significantly less (143% vs. 66%, p < 0.001). CONCLUSIONS: Information obtained from a supine MRI can be used to generate 3D tumor models and rapidly classify breast tumor shapes. The vast majority of invasive cancers and DCIS are not spherical. Knowledge of tumor shape may allow surgeons to excise breast cancer more precisely.


Assuntos
Neoplasias da Mama/patologia , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Mastectomia Segmentar/métodos , Mastectomia/métodos , Carga Tumoral , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade
17.
Breast Cancer Res Treat ; 182(3): 665-677, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32562118

RESUMO

PURPOSE: Circulating tumor DNA in plasma may present a minimally invasive opportunity to identify tumor-derived mutations to inform selection of targeted therapies for individual patients, particularly in cases of oligometastatic disease where biopsy of multiple tumors is impractical. To assess the utility of plasma DNA as a "liquid biopsy" for precision oncology, we tested whether sequencing of plasma DNA is a reliable surrogate for sequencing of tumor DNA to identify targetable genetic alterations. METHODS: Blood and biopsies of 1-3 tumors were obtained from 4 evaluable patients with advanced breast cancer. One patient provided samples from an additional 7 tumors post-mortem. DNA extracted from plasma, tumor tissues, and buffy coat of blood were used for probe-directed capture of all exons in 149 cancer-related genes and massively parallel sequencing. Somatic mutations in DNA from plasma and tumors were identified by comparison to buffy coat DNA. RESULTS: Sequencing of plasma DNA identified 27.94 ± 11.81% (mean ± SD) of mutations detected in a tumor(s) from the same patient; such mutations tended to be present at high allelic frequency. The majority of mutations found in plasma DNA were not found in tumor samples. Mutations were also found in plasma that matched clinically undetectable tumors found post-mortem. CONCLUSIONS: The incomplete overlap of genetic alteration profiles of plasma and tumors warrants caution in the sole reliance of plasma DNA to identify therapeutically targetable alterations in patients and indicates that analysis of plasma DNA complements, but does not replace, tumor DNA profiling. TRIAL REGISTRATION: Subjects were prospectively enrolled in trial NCT01836640 (registered April 22, 2013).


Assuntos
Neoplasias da Mama/genética , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , DNA de Neoplasias/sangue , DNA de Neoplasias/genética , Mutação , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Biópsia Líquida/métodos , Metástase Neoplásica , Prognóstico
18.
Adm Policy Ment Health ; 47(3): 451-467, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31853686

RESUMO

We sought to develop a quality standard for the delivery of psychotherapy for posttraumatic stress disorder (PTSD) that is both consistent with the underlying evidence supporting psychotherapy as a treatment for PTSD and associated with the best levels of symptom improvement. We quantified psychotherapy receipt during the initial year of PTSD treatment in a 10-year national cohort of Department of Veterans Affairs (VA) users who completed patient-reported outcome measurement as part of routine practice. We added progressively stringent measurement requirements. The most stringent requirement was associated with superior outcomes. Quality of psychotherapy for PTSD in the VA improved over time.


Assuntos
Medidas de Resultados Relatados pelo Paciente , Psicoterapia , Indicadores de Qualidade em Assistência à Saúde/tendências , Transtornos de Estresse Pós-Traumáticos/terapia , Adulto , Estudos de Coortes , Bases de Dados Factuais , Prática Clínica Baseada em Evidências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos , Veteranos/psicologia
19.
Adm Policy Ment Health ; 47(4): 648, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32314128

RESUMO

The original version of this article unfortunately contained a mistake. The co-author name was incorrectly published with the middle initial in the author list.

20.
Sensors (Basel) ; 19(3)2019 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-30717339

RESUMO

In driver training, the correct observation of the trainees' operation is the key to ensure the training quality. The operation of the vehicle can be expressed by the vehicle state changes. This paper proposes a driver training model based on a multiple-embedded-sensor net. Six vehicle state parameters are identified as the critical features of the reverse parking machine learning model and represented quantitatively. A multiple-embedded-sensor net-based system mounted on a real vehicle is developed to collect the actual data of the six critical features. The data collected at the same time are bound together and encapsulated into a vector and sequenced by time with a label given by the multiple-embedded-sensor net. All vectors are evaluated by subjective assessment conclusions from experienced driving instructors and the positive ones are used as the training data of the model. The trained model can remind the driver of the next correct operation during training, and can also analyze the improvements after the training. The model has achieved good results in practical application. The experiments prove the validity and reliability of the proposed driver training model.

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