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1.
J Biopharm Stat ; : 1-15, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847351

RESUMO

Bayesian adaptive designs with response adaptive randomization (RAR) have the potential to benefit more participants in a clinical trial. While there are many papers that describe RAR designs and results, there is a scarcity of works reporting the details of RAR implementation from a statistical point exclusively. In this paper, we introduce the statistical methodology and implementation of the trial Changing the Default (CTD). CTD is a single-center prospective RAR comparative effectiveness trial to compare opt-in to opt-out tobacco treatment approaches for hospitalized patients. The design assumed an uninformative prior, conservative initial allocation ratio, and a higher threshold for stopping for success to protect results from statistical bias. A particular emerging concern of RAR designs is the possibility that time trends will occur during the implementation of a trial. If there is a time trend and the analytic plan does not prespecify an appropriate model, this could lead to a biased trial. Adjustment for time trend was not pre-specified in CTD, but post hoc time-adjusted analysis showed no presence of influential drift. This trial was an example of a successful two-armed confirmatory trial with a Bayesian adaptive design using response adaptive randomization.

2.
Environ Toxicol ; 39(6): 3341-3355, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38440848

RESUMO

BACKGROUND: Sepsis remains a crucial global health issue characterized by high mortality rates and a lack of specific treatments. This study aimed to elucidate the molecular mechanisms underlying sepsis and to identify potential therapeutic targets and compounds. METHODS: High-throughput sequencing data from the GEO database (GSE26440 as the training set and GSE13904 and GSE32707 as the validation sets), weighted gene co-expression network analysis (WGCNA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, alongside a combination of PPI and machine learning methods (LASSO and SVM) were utilized. RESULTS: WGCNA identified the black module as positively correlated, and the green module as negatively correlated with sepsis. Further intersections of these module genes with age-related genes yielded 57 sepsis-related genes. GO and KEGG pathway enrichment analysis, PPI, LASSO, and SVM selected six hub aging-related genes: BCL6, FOS, ETS1, ETS2, MAPK14, and MYC. A diagnostic model was constructed based on these six core genes, presenting commendable performance in both the training and validation sets. Notably, ETS1 demonstrated significant differential expression between mild and severe sepsis, indicating its potential as a biomarker of severity. Furthermore, immune infiltration analysis of these six core genes revealed their correlation with most immune cells and immune-related pathways. Additionally, compounds were identified in the traditional Chinese medicine Danshen, which upon further analysis, revealed 354 potential target proteins. GO and KEGG enrichment analysis of these targets indicated a primary enrichment in inflammation and immune-related pathways. A Venn diagram intersects these target proteins, and our aforementioned six core genes yielded three common genes, suggesting the potential efficacy of Danshen in sepsis treatment through these genes. CONCLUSIONS: This study highlights the pivotal roles of age-related genes in the molecular mechanisms of sepsis, offers potential biomarkers, and identifies promising therapeutic compounds, laying a robust foundation for future studies on the treatment of sepsis.


Assuntos
Envelhecimento , Biomarcadores , Sepse , Sepse/tratamento farmacológico , Sepse/genética , Humanos , Biomarcadores/metabolismo , Aprendizado de Máquina , Redes Reguladoras de Genes/efeitos dos fármacos , Perfilação da Expressão Gênica , Ontologia Genética , Bases de Dados Genéticas
3.
JAMA Intern Med ; 183(4): 331-339, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36848129

RESUMO

Importance: Tobacco use causes 7 million deaths per year; most national guidelines require people who use tobacco to opt in to care by affirming they are willing to quit. Use of medications and counseling is low even in advanced economy countries. Objective: To evaluate the efficacy of opt-out care vs opt-in care for people who use tobacco. Design, Setting, and Participants: In Changing the Default (CTD), a Bayesian adaptive population-based randomization trial, eligible patients were randomized into study groups, treated according to group assignment, and debriefed and consented for participation at 1-month follow-up. A total of 1000 adult patients were treated at a tertiary care hospital in Kansas City. Patients were randomized from September 2016 to September 2020; final follow-up was in March 2021. Interventions: At bedside, counselors screened for eligibility, conducted baseline assessment, randomized patients to study group, and provided opt-out care or opt-in care. Counselors and medical staff provided opt-out patients with inpatient nicotine replacement therapy, prescriptions for postdischarge medications, a 2-week medication starter kit, treatment planning, and 4 outpatient counseling calls. Patients could opt out of any or all elements of care. Opt-in patients willing to quit were offered each element of treatment described previously. Opt-in patients who were unwilling to quit received motivational counseling. Main Outcomes and Measures: The main outcomes were biochemically verified abstinence and treatment uptake at 1 month after randomization. Results: Of a total of 1000 eligible adult patients who were randomized, most consented and enrolled (270 [78%] of opt-in patients; 469 [73%] of opt-out patients). Adaptive randomization assigned 345 (64%) to the opt-out group and 645 (36%) to the opt-in group. The mean (SD) age at enrollment was 51.70 (14.56) for opt-out patients and 51.21 (14.80) for opt-out patients. Of 270 opt-in patients, 123 (45.56%) were female, and of 469 opt-out patients, 226 (48.19%) were female. Verified quit rates for the opt-out group vs the opt-in group were 22% vs 16% at month 1 and 19% vs 18% at 6 months. The Bayesian posterior probability that opt-out care was better than opt-in care was 0.97 at 1 month and 0.59 at 6 months. Treatment use for the opt-out group vs the opt-in group was 60% vs 34% for postdischarge cessation medication (bayesian posterior probability of 1.0), and 89% vs 37% for completing at least 1 postdischarge counseling call (bayesian posterior probability of 1.0). The incremental cost-effectiveness ratio was $678.60, representing the cost of each additional quit in the opt-out group. Conclusions and Relevance: In this randomized clinical trial, opt-out care doubled treatment engagement and increased quit attempts, while enhancing patients' sense of agency and alliance with practitioners. Stronger and longer treatment could increase cessation. Trial Registration: ClinicalTrials.gov Identifier: NCT02721082.


Assuntos
Abandono do Hábito de Fumar , Adulto , Humanos , Feminino , Masculino , Abandono do Hábito de Fumar/psicologia , Nicotiana , Assistência ao Convalescente , Teorema de Bayes , Dispositivos para o Abandono do Uso de Tabaco/efeitos adversos , Alta do Paciente
4.
Artigo em Inglês | MEDLINE | ID: mdl-36011811

RESUMO

Smoking during pregnancy and postpartum remains an important public health problem. No known prior study has prospectively examined mutual changes in risk factors and women's smoking trajectory across pregnancy and postpartum. The objective of this study was to report methods used to implement a prospective cohort (Msgs4Moms), present participant baseline characteristics, and compare our sample characteristics to pregnant women from national birth record data. The cohort study was designed to investigate smoking patterns, variables related to tobacco use and abstinence, and tobacco treatment quality across pregnancy through 1-year postpartum. Current smokers or recent quitters were recruited from obstetrics clinics. Analyses included Chi-square and independent sample t-tests using Cohen's d. A total of 62 participants (41 smokers and 21 quitters) were enrolled. Participants were Black (45.2%), White (35.5%), and multiracial (19.3%); 46.8% had post-secondary education; and most were Medicaid-insured (64.5%). Compared with quitters, fewer smokers were employed (65.9 vs 90.5%, Cohen's d = 0.88) and more reported financial strain (61.1% vs 28.6%; Cohen's d = 0.75). Women who continue to smoke during pregnancy cope with multiple social determinants of health. Longitudinal data from this cohort provide intensive data to identify treatment gaps, critical time points, and potential psychosocial variables warranting intervention.


Assuntos
Abandono do Hábito de Fumar , Estudos de Coortes , Feminino , Humanos , Período Pós-Parto , Gravidez , Gestantes/psicologia , Estudos Prospectivos , Abandono do Hábito de Fumar/métodos
5.
Front Med (Lausanne) ; 9: 783931, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35372451

RESUMO

Anxiety disorders are the most common psychiatric diseases, and perioperative factors often increase the incidence of anxiety. However, the mechanism and treatment for perioperative anxiety, especially anesthesia/surgery-induced postoperative anxiety, are largely unknown. Sirtuin 3 (SIRT3) which located in the mitochondria is the NAD-dependent deacetylase protein. SIRT3 mediated oxidative stress is associated with several neuropsychiatric diseases. In addition, hyperpolarization-activated cyclic nucleotide-gated 1 (HCN1) channel is also reported involved in anxiety symptoms. The purpose was to assess the role of SIRT3 on postoperative anxiety like behavior in C57/BL6 mice. We found that SIRT3 level reduced and HCN1 expression level increased in mice medial prefrontal cortex (mPFC) as well as anxiety like behavior postoperatively. In interventional research, SIRT3 adeno-associated virus vector or control vector was injected into the mPFC brain region. Enzyme-linked immunosorbent assay, immunofluorescence staining, and western blotting were employed to detect oxidative stress reactions and HCN1 channel activity. SIRT3 overexpression attenuated postoperative anxiety in mice. Superoxide dismutase 2 (SOD2) acetylation levels, SOD2 oxidative stress activity, mitochondrial membrane potential levels, and HCN1 channels were also inhibited by SIRT3 overexpression. Furthermore, the HCN1 channel inhibitor ZD7288 significantly protected against anesthesia/surgery-induced anxiety, but without SIRT3/ac-SOD2 expression or oxidative stress changes. Our results suggest that SIRT3 may achieve antianxiety effects through regulation of SOD2 acetylation-mediated oxidative stress and HCN1 channels in the mPFC, further strengthening the therapeutic potential of targeting SIRT3 for anesthesia/surgery-induced anxiety-like behavior.

6.
Pharm Stat ; 20(3): 573-596, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33463906

RESUMO

Patients with different characteristics (e.g., biomarkers, risk factors) may have different responses to the same medicine. Personalized medicine clinical studies that are designed to identify patient subgroup treatment efficacies can benefit patients and save medical resources. However, subgroup treatment effect identification complicates the study design in consideration of desired operating characteristics. We investigate three Bayesian adaptive models for subgroup treatment effect identification: pairwise independent, hierarchical, and cluster hierarchical achieved via Dirichlet Process (DP). The impact of interim analysis and longitudinal data modeling on the personalized medicine study design is also explored. Interim analysis is considered since they can accelerate personalized medicine studies in cases where early stopping rules for success or futility are met. We apply integrated two-component prediction method (ITP) for longitudinal data simulation, and simple linear regression for longitudinal data imputation to optimize the study design. The designs' performance in terms of power for the subgroup treatment effects and overall treatment effect, sample size, and study duration are investigated via simulation. We found the hierarchical model is an optimal approach to identifying subgroup treatment effects, and the cluster hierarchical model is an excellent alternative approach in cases where sufficient information is not available for specifying the priors. The interim analysis introduction to the study design lead to the trade-off between power and expected sample size via the adjustment of the early stopping criteria. The introduction of the longitudinal modeling slightly improves the power. These findings can be applied to future personalized medicine studies with discrete or time-to-event endpoints.


Assuntos
Ensaios Clínicos como Assunto , Medicina de Precisão , Projetos de Pesquisa , Teorema de Bayes , Humanos , Futilidade Médica , Tamanho da Amostra
7.
Skeletal Radiol ; 48(12): 1891-1898, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31134315

RESUMO

OBJECTIVE: Hook of hamate fracture, the most common swing-related wrist fracture, is commonly seen in high-level athletes. The fracture is rarely diagnosed on routine wrist radiographs, thus generally requiring CT or MR for diagnosis. Surgical excision has a high success rate, however diagnostic delay contributes to a high complication rate. Radiographic signs of hook of hamate fracture have been published, but uncertainty of the diagnostic accuracy limits application. The purpose of this study is to determine accuracy and interobserver reliability of radiographic signs of hook of hamate. MATERIALS AND METHODS: This retrospective case-control study evaluated wrist radiographs of 50 patients, including 24 positive and 26 negative, for hook of hamate fracture, each proven by CT or MR. Five reviewers performed blinded, randomized evaluation of radiographs documenting whether the hook of hamate was normal or fractured, and if fractured, the radiographic signs present (ring sign, ghostly shadow, and diffuse sclerosis) and views that contributed to diagnosis. RESULTS: Radiographic signs demonstrated high sensitivity (85%; 95% CI: 77-91), specificity (92%; 95% CI: 86-96), and accuracy (89%; 95% CI: 84-92) with substantial interobserver reliability (k = 0.652). The ring sign was the most sensitive radiographic sign. Diagnosis was most often supported by the oblique view (38%) and rarely the lateral view (15%). CONCLUSIONS: Radiographic signs of hook of hamate fracture on routine radiographs can accurately and reliably diagnose hook of hamate fractures. Evaluation for discontinuity of the cortical ring will optimize sensitivity, allowing for timely diagnosis and treatment, and a reduction of complications.


Assuntos
Fraturas Ósseas/diagnóstico por imagem , Hamato/diagnóstico por imagem , Hamato/lesões , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Traumatismos do Punho/diagnóstico por imagem , Adulto , Traumatismos em Atletas/diagnóstico por imagem , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
8.
Stat Med ; 37(19): 2900-2901, 2018 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-30294062

RESUMO

This paper is the letter to the editor regarding several comments on 'Tutorial on statistical considerations on subgroup analysis in confirmatory clinical trials.'


Assuntos
Projetos de Pesquisa , Tamanho da Amostra
9.
J Nutr Educ Behav ; 50(3): 247-257.e1, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29246567

RESUMO

OBJECTIVE: To test the reliability and validity of the Nutrition Literacy Assessment Instrument (NLit) in adult primary care and identify the relationship between nutrition literacy and diet quality. DESIGN: This instrument validation study included a cross-sectional sample participating in up to 2 visits 1 month apart. SETTING/PARTICIPANTS: A total of 429 adults with nutrition-related chronic disease were recruited from clinics and a patient registry affiliated with a Midwestern university medical center. MAIN OUTCOME MEASURES: Nutrition literacy was measured by the NLit, which was composed of 6 subscales: nutrition and health, energy sources in food, food label and numeracy, household food measurement, food groups, and consumer skills. Diet quality was measured by Healthy Eating Index-2010 with nutrient data from Diet History Questionnaire II surveys. ANALYSIS: The researchers measured factor validity and reliability by using binary confirmatory factor analysis; test-retest reliability was measured by Pearson r and the intraclass correlation coefficient, and relationships between nutrition literacy and diet quality were analyzed by linear regression. RESULTS: The NLit demonstrated substantial factor validity and reliability (0.97; confidence interval, 0.96-0.98) and test-retest reliability (0.88; confidence interval, 0.85-0.90). Nutrition literacy was the most significant predictor of diet quality (ß = .17; multivariate coefficient = 0.10; P < .001). CONCLUSIONS: The NLit is a valid and reliable tool for measuring nutrition literacy in adult primary care patients.


Assuntos
Letramento em Saúde , Avaliação Nutricional , Inquéritos e Questionários/normas , Adulto , Idoso , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
10.
BMC Pregnancy Childbirth ; 17(1): 18, 2017 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-28068927

RESUMO

BACKGROUND: Despite the widely recognized association between the severity of early preterm birth (ePTB) and its related severe diseases, little is known about the potential risk factors of ePTB and the sub-population with high risk of ePTB. Moreover, motivated by a future confirmatory clinical trial to identify whether supplementing pregnant women with docosahexaenoic acid (DHA) has a different effect on the risk subgroup population or not in terms of ePTB prevalence, this study aims to identify potential risk subgroups and risk factors for ePTB, defined as babies born less than 34 weeks of gestation. METHODS: The analysis data (N = 3,994,872) were obtained from CDC and NCHS' 2014 Natality public data file. The sample was split into independent training and validation cohorts for model generation and model assessment, respectively. Logistic regression and CART models were used to examine potential ePTB risk predictors and their interactions, including mothers' age, nativity, race, Hispanic origin, marital status, education, pre-pregnancy smoking status, pre-pregnancy BMI, pre-pregnancy diabetes status, pre-pregnancy hypertension status, previous preterm birth status, infertility treatment usage status, fertility enhancing drug usage status, and delivery payment source. RESULTS: Both logistic regression models with either 14 or 10 ePTB risk factors produced the same C-index (0.646) based on the training cohort. The C-index of the logistic regression model based on 10 predictors was 0.645 for the validation cohort. Both C-indexes indicated a good discrimination and acceptable model fit. The CART model identified preterm birth history and race as the most important risk factors, and revealed that the subgroup with a preterm birth history and a race designation as Black had the highest risk for ePTB. The c-index and misclassification rate were 0.579 and 0.034 for the training cohort, and 0.578 and 0.034 for the validation cohort, respectively. CONCLUSIONS: This study revealed 14 maternal characteristic variables that reliably identified risk for ePTB through either logistic regression model and/or a CART model. Moreover, both models efficiently identify risk subgroups for further enrichment clinical trial design.


Assuntos
Ensaios Clínicos como Assunto , Lactente Extremamente Prematuro , Nascimento Prematuro/etiologia , Grupos Raciais/estatística & dados numéricos , Projetos de Pesquisa , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Feminino , Hispânico ou Latino/estatística & dados numéricos , Humanos , Hipertensão Induzida pela Gravidez/epidemiologia , Hipertensão Induzida pela Gravidez/etiologia , Recém-Nascido , Modelos Logísticos , Idade Materna , Paridade , Gravidez , Nascimento Prematuro/epidemiologia , Prevalência , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Estados Unidos/epidemiologia
11.
Medicine (Baltimore) ; 94(45): e1872, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26559255

RESUMO

Although previous reports have linked DNA damage with both transmissions across generations as well as our own survival, it is unknown how to reverse the lesion. Based on the data from a Randomized, Double-blind, Placebo Controlled Clinical Trial, this study aimed to assess the efficacy of folic acid supplementation (FAS) on DNA oxidative damage reversal.In this randomized clinical trial (RCT), a total of 450 participants were enrolled and randomly assigned to 3 groups to receive folic acid (FA) 0.4 mg/day (low-FA), 0.8 mg/day (high-FA), or placebo (control) for 8 weeks. The urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and creatinine (Cr) concentration at pre- and post-FAS were measured with modified enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC), respectively. A multivariate general linear model was applied to assess the individual effects of FAS and the joint effects between FAS and hypercholesterolemia on oxidative DNA damage improvement. This clinical trial was registered with ClinicalTrials.gov, number NCT02235948.Of the 438 subjects that received FA fortification or placebo, the median (first quartile, third quartile) of urinary 8-OHdG/Cr for placebo, low-FA, and high-FA groups were 58.19 (43.90, 82.26), 53.51 (38.97, 72.74), 54.73 (39.58, 76.63) ng/mg at baseline and 57.77 (44.35, 81.33), 51.73 (38.20, 71.30), and 50.65 (37.64, 76.17) ng/mg at the 56th day, respectively. A significant decrease of urinary 8-OHdG was observed after 56 days FA fortification (P < 0.001). Compared with the placebo, after adjusting for some potential confounding factors, including the baseline urinary 8-OHdG/Cr, the urinary 8-OHdG/Cr concentration significantly decreased after 56 days FAS [ß (95% confidence interval) = -0.88 (-1.62, -0.14) and P = 0.020 for low-FA; and ß (95% confidence interval) = -2.68 (-3.42, -1.94) and P < 0.001 for high-FA] in a dose-response fashion (Ptrend < 0.001). Test of interaction between hypercholesterolemia and FA supplementation on urinary 8-OHdG reduction was significant (P = 0.001).The present study demonstrates that FA fortification is independently linked to the reduction of urinary 8-OHdG/Cr in a dose-related pattern, which suggests that FA is beneficial to protect against oxidative damage to DNA. This effect is apparently stronger in those with hypercholesterolemia. The authors provide a new insight into the prevention and reversal of oxidative DNA damage.


Assuntos
Dano ao DNA/efeitos dos fármacos , Ácido Fólico/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Complexo Vitamínico B/uso terapêutico , 8-Hidroxi-2'-Desoxiguanosina , Adolescente , Adulto , Idoso , Creatinina/urina , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Hipercolesterolemia/complicações , Hipercolesterolemia/metabolismo , Masculino , Pessoa de Meia-Idade , Adulto Jovem
12.
Toxicol Appl Pharmacol ; 283(3): 198-209, 2015 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-25625412

RESUMO

Arsenic exposure is postulated to modify microRNA (miRNA) expression, leading to changes of gene expression and toxicities, but studies relating the responses of miRNAs to arsenic exposure are lacking, especially with respect to in vivo studies. We utilized high-throughput sequencing technology and generated miRNA expression profiles of liver tissues from Sprague Dawley (SD) rats exposed to various concentrations of sodium arsenite (0, 0.1, 1, 10 and 100mg/L) for 60days. Unsupervised hierarchical clustering analysis of the miRNA expression profiles clustered the SD rats into different groups based on the arsenic exposure status, indicating a highly significant association between arsenic exposure and cluster membership (p-value of 0.0012). Multiple miRNA expressions were altered by arsenic in an exposure concentration-dependent manner. Among the identified arsenic-responsive miRNAs, several are predicted to target Nfe2l2-regulated antioxidant genes, including glutamate-cysteine ligase (GCL) catalytic subunit (GCLC) and modifier subunit (GCLM) which are involved in glutathione (GSH) synthesis. Exposure to low concentrations of arsenic increased mRNA expression for Gclc and Gclm, while high concentrations significantly reduced their expression, which were correlated to changes in hepatic GCL activity and GSH level. Moreover, our data suggested that other mechanisms, e.g., miRNAs, rather than Nfe2l2-signaling pathway, could be involved in the regulation of mRNA expression of Gclc and Gclm post-arsenic exposure in vivo. Together, our findings show that arsenic exposure disrupts the genome-wide expression of miRNAs in vivo, which could lead to the biological consequence, such as an altered balance of antioxidant defense and oxidative stress.


Assuntos
Arsenitos/toxicidade , Carcinógenos Ambientais/toxicidade , Fígado/efeitos dos fármacos , MicroRNAs/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Compostos de Sódio/toxicidade , Animais , Análise por Conglomerados , Relação Dose-Resposta a Droga , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Glutamato-Cisteína Ligase/genética , Glutamato-Cisteína Ligase/metabolismo , Glutationa/metabolismo , Fígado/metabolismo , Fígado/patologia , Masculino , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Ratos Sprague-Dawley , Fatores de Tempo
13.
Zhonghua Liu Xing Bing Xue Za Zhi ; 35(7): 802-5, 2014 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-25294070

RESUMO

OBJECTIVE: To explore the association between dyslipidemia and the level of 8-OHdG/Cr in urine among a population exposed to chronic arsenic. METHODS: Four hundred and seven subjects were randomly selected in an arsenic-affected area in Inner Mongolia. After blood biochemical examination, all the subjects were divided into 4 groups based on the results of total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C)and low density lipoprotein cholesterol (LDL-C). The groups consisted of hypercholesterolemia, HDL-C ratio anomaly, combined hypercholesterolemia and HDL-C ratio anomaly, as well as a normal lipid group. Urine samples were collected and 8-OHdG/Cr was measured using the ELISA method. A generalized linear mixed model was used to analyze the association between dyslipidemia and 8-OHdG/Cr. RESULTS: The levels of 8-OHdG/Cr as 55.73 (39.90-79.94) ng/mg, 58.08 (44.94-69.91)ng/mg, 65.28 (49.29-92.95) ng/mg and 51.43 (36.86-68.57) ng/mgin the HDL-C ratio anomaly, hypercholesterolemia, combined hypercholesterolemia and HDL-C ratio anomaly groups and the control group, respectively, which showed significant differences on the levels of 8-OHdG/Cr in the four groups(P = 0.006). From the linear regression analysis results showed that the 8-OHdG/Cr level in combined hypercholesterolemia and HDL-C ratio anomaly group was higher (4.25 ± 0.55 ng/mg) than in the control group (3.96 ± 0.55 ng/mg) (P = 0.018). After adjusting for important covariates, there was a linear trend between the levels of 8-OHdG/Cr and dyslipidemia (P = 0.016). CONCLUSION: Data from our study showed a linear relation between hypercholesterolemia, HDL-C ratio anomaly and the 8-OHdG/Cr level, suggesting that dyslipidemia was associated with oxidative DNA damage among those .


Assuntos
Intoxicação por Arsênico/epidemiologia , Dano ao DNA , Dislipidemias/epidemiologia , 8-Hidroxi-2'-Desoxiguanosina , Adolescente , Adulto , Idoso , HDL-Colesterol/sangue , Doença Crônica , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangue , Adulto Jovem
14.
Hypertens Res ; 36(4): 334-41, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23324866

RESUMO

The cardio-ankle vascular index (CAVI) has been widely accepted as a good indicator of arteriosclerosis. However, the lack of a reliable diagnostic criterion for CAVI hampers the proper clinical screening for arteriosclerosis using CAVI and impedes the prompt treatment of cardiovascular disease (CVD). There is an urgent need to determine a criterion for CAVI in arteriosclerosis prevention. We conducted a cross-sectional study to determine this criterion based on receiver operating characteristic (ROC) analyses in a Chinese population consisting of 328 participants. CAVI was measured in duplicate, and carotid ultrasound detection was performed in a quiet environment by well-trained physicians. After multivariate adjustment, CAVI was positively associated with the risk of carotid arteriosclerosis. Compared with participants in the lowest tertile of CAVI (5.15-7.40), those in the medium (7.41-8.65) and highest (8.66-13.60) tertiles had odds ratios (95% confidence interval) of 2.2 (1.0, 4.9) and 4.4 (1.5, 13.3), respectively, for developing carotid arteriosclerosis (P trend=0.007). The areas under the ROC curve (AUC) of the male, female and pooled populations were 0.789, 0.897 and 0.856, respectively. The cutoff point of CAVI≥8.0 resulted in the largest sensitivity and specificity. Furthermore, CAVI and age acted synergistically to increase the risk of carotid arteriosclerosis. CAVI≥8.0 may be an optimal cutoff point for carotid arteriosclerosis prediction. The older population with higher CAVI scores had a higher risk of carotid arteriosclerosis. Additional large prospective studies are needed to confirm our findings.


Assuntos
Tornozelo/irrigação sanguínea , Doenças das Artérias Carótidas/fisiopatologia , Rigidez Vascular/fisiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Povo Asiático , Velocidade do Fluxo Sanguíneo , Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/diagnóstico , Doenças das Artérias Carótidas/diagnóstico por imagem , Estudos Transversais , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/patologia , Valor Preditivo dos Testes , Curva ROC , Valores de Referência , Fatores de Risco , Fatores Socioeconômicos , Ultrassonografia , Adulto Jovem
15.
J Hazard Mater ; 262: 1154-8, 2013 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-23069333

RESUMO

Arsenic increases the risk and incidence of cardiovascular disease. To explore the impact of long-term exposure to low-level arsenic in drinking water on blood pressure including pulse pressure (PP) and mean arterial blood pressure (MAP), a cross-sectional study was conducted in 2010 in which the blood pressure of 405 villagers was measured, who had been drinking water with an inorganic arsenic content <50 µg/L. A multivariate logistic regression model was used to estimate odds ratios and 95% confidence intervals. After adjusting for age, gender, Body Mass Index (BMI), alcohol consumption and smoking, the odds ratios showed a 1.45-fold (95%CI: 0.63-3.35) increase in the group with >30-50 years of arsenic exposure and a 2.95-fold (95%CI: 1.31-6.67) increase in the group with >50 years exposure. Furthermore, the odds ratio for prevalence of abnormal PP and MAP were 1.06 (95%CI: 0.24-4.66) and 0.87 (95%CI: 0.36-2.14) in the group with >30-50 years of exposure, and were 2.46 (95%CI: 0.87-6.97) and 3.75 (95%CI: 1.61-8.71) for the group with >50 years exposure, compared to the group with arsenic exposure ≤ 30 years respectively. Significant trends for Hypertension (p<0.0001), PP (p<0.0001) and MAP (p=0.0016) were found. The prevalence of hypertension and abnormal PP as well as MAP is marked among a low-level arsenic exposure population, and significantly increases with the duration of arsenic exposure.


Assuntos
Arsênio/análise , Água Potável , Hipertensão/epidemiologia , Poluentes Químicos da Água/toxicidade , Adolescente , Adulto , Idoso , Consumo de Bebidas Alcoólicas , Arsênio/toxicidade , Pressão Sanguínea , Índice de Massa Corporal , Estudos Transversais , Exposição Ambiental , Feminino , Humanos , Hipertensão/diagnóstico , Masculino , Pessoa de Meia-Idade , Mongólia/epidemiologia , Análise Multivariada , Razão de Chances , Abastecimento de Água , Adulto Jovem
16.
Chemosphere ; 80(9): 978-81, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20646734

RESUMO

UNLABELLED: Long term exposure to arsenic can cause adverse health effects and lead to different levels of disability. The prevalence of arsenical dermatosis is as high as 40% in the Hetao Plain area of Inner Mongolia, but the association between exposure to arsenic in drinking water and the occurrence of disability has not yet been fully examined. The aim of this study was to investigate the prevalence of disability in arsenic-affected villages in Inner Mongolia, China. METHODS: A cross-sectional study was performed to examine the prevalence of disability. A total of 320 villagers in the age range of 20-39 years were interviewed and examined for disability and arsenical skin lesions. The subjects were classified into a high arsenic group (50 microg L(-1)) and a low arsenic group (<50 microg L(-1)). The relationship between levels of arsenic in drinking water and disability was analyzed using multivariate logistic regression models to estimate the odds ratios and 95% confidence intervals. RESULTS: The prevalence of disability was 6.88% in the arsenic affected area of Inner Mongolia and 24.72% in the arsenic group 50 microg L(-1). A strong correlation was found between disability and arsenical skin lesions (OR=86.39, 95%CI: 25.45-293.20). CONCLUSION: This suggests that the level of arsenic exposure is a major risk factor for disability. Further research is needed to place the results in a wider context and to determine the exact relationship between arsenic exposure and disability.


Assuntos
Arsênio/toxicidade , Pessoas com Deficiência , Exposição Ambiental/efeitos adversos , Poluentes Químicos da Água/toxicidade , Adulto , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Entrevistas como Assunto , Masculino , Razão de Chances , Fatores de Risco , Dermatopatias/induzido quimicamente , Dermatopatias/epidemiologia
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