Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 123
Filtrar
1.
PLoS One ; 15(12): e0244728, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33382778

RESUMO

BACKGROUND: There are no epidemiologic data on the relation of depression before colorectal cancer diagnosis to colorectal cancer mortality among women with colorectal cancer, especially those who are postmenopausal. Our aim was to fill this research gap. METHODS: We analyzed data from a large prospective cohort in the US, the Women's Health Initiative (WHI). The study included 2,396 women with incident colorectal cancer, assessed for depressive symptoms and antidepressant use before cancer diagnosis at baseline (screening visit in the WHI study) during 1993-1998. Participants were followed up from cancer diagnosis till 2018. We used Cox proportional hazards regression to estimate adjusted hazard ratios (HRs) between depression (depressive symptoms or antidepressant use) at baseline, and all-cause mortality and colorectal cancer-specific mortality. RESULTS: Among women with colorectal cancer, there was no association between baseline depression and all-cause mortality or colorectal cancer-specific mortality after adjusting for age or multiple covariates. CONCLUSION: Among women with colorectal cancer, there was no statistically significant association between depression before colorectal cancer diagnosis and all-cause mortality or colorectal cancer-specific mortality. Further studies are warranted to assess depressive symptoms and antidepressant use, measured at multiple points from baseline to diagnosis, and their interactions with specific types of colorectal cancer treatment on the risk of death from colorectal cancer.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33335021

RESUMO

BACKGROUND: Female hormones may play roles during renal cell carcinoma (RCC) carcinogenesis. The aims of this study were to investigate associations between hysterectomy, oophorectomy, and risk of RCC and to assess whether the associations were modified by exogenous estrogen, commonly used among women who have undergone hysterectomy. METHODS: Postmenopausal women (n = 144,599) ages 50-79 years at enrollment (1993-1998) in the Women's Health Initiative were followed for a mean of 15.9 years. Hysterectomy and oophorectomy were self-reported. Incident RCC cases were confirmed by physician review of medical records and pathology reports. Multivariable Cox proportional hazards modeling was used to estimate hazard ratios (HR) and 95% confidence intervals (CI), adjusting for potential confounders. RESULTS: A total of 583 women developed RCC during follow-up. We observed that hysterectomy, regardless of oophorectomy status, was significantly associated with an increased risk of RCC (HR, 1.28; 95% CI, 1.03-1.60). The association appeared to be more pronounced in women with age at hysterectomy younger than 40 years (HR, 1.34; 95% CI, 1.01-1.80) or older than 55 years (HR, 1.52; 95% CI, 1.01-2.29). Oophorectomy was not significantly associated with risk of RCC. There was no evidence that exogenous estrogen use modified the association between hysterectomy and risk of RCC. CONCLUSIONS: In this large prospective study, we showed that women with a history of hysterectomy had 28% increased risk of RCC, and this finding was not modified by exogenous hormone use. IMPACT: If our findings are confirmed, women should be made aware of increased risk of RCC when considering hysterectomy.

3.
Cancer ; 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33151547

RESUMO

BACKGROUND: Cardiometabolic abnormalities are a leading cause of death among women, including women with cancer. METHODS: This study examined the association between prediagnosis cardiovascular health and total and cause-specific mortality among 12,076 postmenopausal women who developed local- or regional-stage invasive cancer in the Women's Health Initiative (WHI). Cardiovascular risk factors included waist circumference, hypertension, high cholesterol, and type 2 diabetes. Obesity-related cancers included breast cancer, colorectal cancer, endometrial cancer, kidney cancer, pancreatic cancer, ovarian cancer, stomach cancer, liver cancer, and non-Hodgkin lymphoma. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for important predictors of survival. RESULTS: After a median follow-up of 10.0 years from the date of the cancer diagnosis, there were 3607 total deaths, with 1546 (43%) due to cancer. Most participants (62.9%) had 1 or 2 cardiometabolic risk factors, and 8.1% had 3 or 4. In adjusted models, women with 3 to 4 risk factors (vs none) had a higher risk of all-cause mortality (HR, 1.99; 95% CI, 1.73-2.30), death due to cardiovascular disease (CVD) (HR, 4.01; 95% CI, 2.88-5.57), cancer-specific mortality (HR, 1.37; 95% CI, 1.1-1.72), and other-cause mortality (HR, 2.14; 95% CI, 1.70-2.69). A higher waist circumference was associated with greater all-cause mortality (HR, 1.17; 95% CI, 1.06-1.30) and cancer-specific mortality (HR, 1.22; 95% CI, 1.04-1.42). CONCLUSIONS: Among postmenopausal women diagnosed with cancer in the WHI, cardiometabolic risk factors before the cancer diagnosis were associated with greater all-cause, CVD, cancer-specific, and other-cause mortality. These results raise hypotheses regarding potential clinical intervention strategies targeting cardiometabolic abnormalities that require future prospective studies for confirmation. LAY SUMMARY: This study uses information from the Women's Health Initiative (WHI) to find out whether cardiac risk factors are related to a greater risk of dying among older women with cancer. The WHI is the largest study of medical problems faced by older women in this country. The results show that women who have 3 or 4 risk factors are more likely to die of any cause, heart disease, or cancer in comparison with women with no risk factors. It is concluded that interventions to help to lower the burden of cardiac risk factors can have an important impact on survivorship among women with cancer.

4.
Environ Health ; 19(1): 111, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33153486

RESUMO

BACKGROUND: Exposure to particulate matter air pollution has been associated with cardiovascular disease (CVD) morbidity and mortality; however, most studies have focused on fine particulate matter (PM2.5) exposure and CVD. Coarse particulate matter (PM10-2.5) exposure has not been extensively studied, particularly for long-term exposure, and the biological mechanisms remain uncertain. METHODS: We examined the association between ambient concentrations of PM10-2.5 and inflammatory and hemostatic makers that have been linked to CVD. Annual questionnaire and clinical data were obtained from 1694 women (≥ 55 years old in 1999) enrolled in the longitudinal Study of Women's Health Across the Nation (SWAN) at six study sites from 1999 to 2004. Residential locations and the USEPA air monitoring network measurements were used to assign exposure to one-year PM10-2.5, as well as co-pollutants. Linear mixed-effects regression models were used to describe the association between PM10-2.5 exposure and markers, including demographic, health and other covariates. RESULTS: Each interquartile (4 µg/m3) increase in one-year PM10-2.5 exposure was associated with a 5.5% (95% confidence interval [CI]: 1.8, 9.4%) increase in levels of plasminogen activator inhibitor-1 (PAI-1) and 4.1% (95% CI: - 0.1, 8.6%) increase in high-sensitivity C-creative Protein (hs-CRP). Stratified analyses suggested that the association with PAI-1 was particularly strong in some subgroups, including women who were peri-menopausal, were less educated, had a body mass index lower than 25, and reported low alcohol consumption. The association between PM10-2.5 and PAI-1 remained unchanged with adjustment for PM2.5, ozone, nitrogen dioxide, and carbon monoxide. CONCLUSIONS: Long-term PM10-2.5 exposure may be associated with changes in coagulation independently from PM2.5, and thus, contribute to CVD risk in midlife women.

5.
J Am Coll Radiol ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33212069

RESUMO

PURPOSE: The aim of this study was to examine radiologists' beliefs about existing guidelines for pulmonary nodule evaluation. METHODS: A self-administered survey was developed to ascertain awareness of, agreement with, and adherence to published guidelines, including those from the Fleischner Society and the Lung CT Screening Reporting and Data System (Lung-RADS™). Surveys were distributed to 514 radiologists at 13 health care systems that are participating in a large, pragmatic trial of pulmonary nodule evaluation. Prespecified comparisons were made among groups defined by type of health system, years of experience, reader volume, and study arm. RESULTS: The response rate was 26.3%. Respondents were most familiar with guidelines from Fleischner (94%) and Lung-RADS (71%). For both incidental and screening-detected nodules, self-reported adherence to preferred guidelines was very high (97% and 94%, respectively), and most respondents believed that the benefits of adherence outweigh the harms (81% and 74%, respectively). Underlying evidence was thought to be high in quality by 68% of respondents for screening-detected nodules and 41% for incidental nodules. Approximately 70% of respondents believed that the frequency of recommended follow-up was "just right" for both guidelines. Radiologists who practice in nonintegrated health care systems were more likely to believe that the evidence was high in quality (79.5% vs 57.1%) and that the benefits of adherence outweigh the harms (85.1% vs 67.5%). Low-volume readers had lower awareness and self-reported adherence than higher volume readers. CONCLUSIONS: Radiologists reported high levels of familiarity and agreement with and adherence to guidelines for pulmonary nodule evaluation, but many overestimated the quality of evidence in support of the recommendations.

7.
J Acad Nutr Diet ; 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32763064

RESUMO

BACKGROUND: Laboratory and animal studies suggest an inverse association between chocolate consumption and the risk of cancer. Epidemiological studies have yielded inconsistent evidence. OBJECTIVE: To assess the association of chocolate candy consumption with incident, invasive total, breast, colorectal, and lung cancers in a large cohort of postmenopausal American women. DESIGN: Prospective cohort study with a mean 14.8-year follow-up. Chocolate candy intake was assessed by food frequency questionnaire. Invasive cancer events were assessed by physician adjudication. PARTICIPANTS/SETTING: The Women's Health Initiative Study enrolled 161,808 postmenopausal women at 40 clinical centers nationwide between 1993 and 1998. Of these women, 114,281 with plausible food frequency or biometric data and no missing data on chocolate candy exposure were selected for analysis. MAIN OUTCOME MEASURES: Cancer risk in quartiles of chocolate candy consumption with the first quartile as referent. STATISTICAL ANALYSES: Multivariable Cox regression was used to calculate hazard ratios and 95% confidence intervals. RESULTS: There were 16,164 documented incident invasive cancers, representing an incidence rate of 17.0 per 100 participants and 12.3 per 1000 person years during follow-up among participants without any preexisting cancers or missing outcome data. There were no statistically significant associations for total invasive cancer (P-linear = .47, P-curvature = .14), or invasive breast cancer (P-linear = .77, P-curvature = .26). For colorectal cancer P-linear was .02, P-curvature was .03, and compared with women eating a 1 oz (28.4 g) chocolate candy serving <1 time per month, the hazard ratio for ≥1.5 times/wk was 1.18 (95% confidence interval: 1.04-1.35). This result may be attributable to the excess adiposity associated with frequent chocolate candy consumption. CONCLUSIONS: In the Women's Health Initiative, there was no significant association between chocolate candy consumption and invasive total or breast cancer. There was a modest 18% higher risk of invasive colorectal cancer for women who ate chocolate candy at least 1.5 times/wk. These results require confirmation.

8.
Mol Pharmacol ; 98(4): 351-363, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32764093

RESUMO

Ryanodine receptor (RYR) mutations confer stress-triggered malignant hyperthermia (MH) susceptibility. Dietary caffeine (CAF) is the most commonly consumed psychoactive compound by humans. CAF-triggered Ca2+ release and its influences on skeletal muscle contractility are widely used as experimental tools to study RYR function/dysfunction and diagnose MH susceptibility. We hypothesize that dietary CAF achieving blood levels measured in human plasma exacerbates the penetrance of RYR1 MH susceptibility mutations triggered by gaseous anesthetic, affecting both central and peripheral adverse responses. Heterozygous R163C-RYR1 (HET) MH susceptible mice are used to investigate the influences of dietary CAF on both peripheral and central responses before and after induction of halothane (HAL) maintenance anesthesia under experimental conditions that maintain normal core body temperature. HET mice receiving CAF (plasma CAF 893 ng/ml) have significantly shorter times to respiratory arrest compared with wild type, without altering blood chemistry or displaying hyperthermia or muscle rigor. Intraperitoneal bolus dantrolene before HAL prolongs time to respiratory arrest. A pilot electrographic study using subcutaneous electrodes reveals that dietary CAF does not alter baseline electroencephalogram (EEG) total power, but significantly shortens delay to isoelectric EEG, which precedes respiratory and cardiac arrest. CAF ± HAL are studied on RYR1 single-channel currents and HET myotubes to define molecular mechanisms of gene-by-environment synergism. Strong pharmacological synergism between CAF and HAL is demonstrated in both single-channel and myotube preparations. Central and peripheral nervous systems mediate adverse responses to HAL in a HET model of MH susceptibility exposed to dietary CAF, a modifiable lifestyle factor that may mitigate risks of acute and chronic diseases associated with RYR1 mutations. SIGNIFICANCE STATEMENT: Dietary caffeine at a human-relevant dose synergizes adverse peripheral and central responses to anesthesia in malignant hyperthermia susceptible mice. Synergism of these drugs can be attributed to their actions at ryanodine receptors.


Assuntos
Cafeína/efeitos adversos , Dantroleno/efeitos adversos , Halotano/efeitos adversos , Hipertermia Maligna/fisiopatologia , Fibras Musculares Esqueléticas/fisiologia , Mutação , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Animais , Cafeína/farmacologia , Dantroleno/administração & dosagem , Modelos Animais de Doenças , Sinergismo Farmacológico , Eletroencefalografia/instrumentação , Feminino , Halotano/administração & dosagem , Heterozigoto , Humanos , Injeções Intraperitoneais , Masculino , Hipertermia Maligna/genética , Camundongos , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo
9.
JAMA Netw Open ; 3(6): e207227, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32602908

RESUMO

Importance: Interval breast cancers (IBCs) are cancers that emerge after a mammogram with negative results but before the patient's next scheduled screening. Interval breast cancer has a worse prognosis than cancers detected by screening; however, it is unknown whether the length of the interscreening period is associated with prognostic features and mortality. Objective: To compare the prognostic features and mortality rate of women with IBCs diagnosed within 1 year or between 1 and 2.5 years of a mammogram with negative results with the prognostic features and mortality rate of women with breast cancers detected by screening. Design, Setting, and Participants: This cohort study used mammography data, tumor characteristics, and patient demographic data from the Women's Health Initiative study, which recruited participants from 1993 to 1998 and followed up with participants for a median of 19 years. The present study sample for these analyses included women aged 50 to 79 years who participated in the Women's Health Initiative study and includes data collected through March 31, 2018. There were 5455 incidents of breast cancer; only 3019 women compliant with screening were retained in analyses. Statistical analysis was performed from October 25, 2018, to November 24, 2019. Breast cancers detected by screening and IBCs were defined based on mammogram history, date of last mammogram, type of visit, and results of examination. Interval breast cancers were subdivided into those occurring within 1 year or between 1 and 2.5 years after the last protocol-mandated mammogram with negative results. Main Outcomes and Measures: The primary outcome of this study was breast cancer-specific mortality for each case of breast cancer detected by screening and IBCs detected within 1 year or between 1 and 2.5 years from a mammogram with negative results. Secondary outcomes included prognostic and tumor characteristics for each group. Comparisons between groups were made using the t test, the χ2 test, and Fine-Gray multivariable cumulative incidence regression analyses. Results: Among the 3019 participants in this analysis, all were women with a mean (SD) age of 63.1 (6.8) years at enrollment and 68.5 (7.1) years at diagnosis. A total of 1050 cases of IBC were identified, with 324 (30.9%) diagnosed within 1 year from a mammogram with negative results and 726 (69.1%) diagnosed between 1 and 2.5 years after last mammogram with negative results. The remaining 1969 cases were breast cancers detected by screening. Interval breast cancers diagnosed within 1 year from a mammogram with negative results had significantly more lobular histologic characteristics (13.0% vs. 8.1%), a larger tumor size (1.97 cm vs 1.43 cm), a higher clinical stage (28.4% vs 17.3% regional and 3.7% vs 0.6% distant), and more lymph node involvement (27.1% vs 17.0%) than cancers detected by screening. Unadjusted breast cancer-specific mortality hazard ratios were significantly higher for IBCs diagnosed within 1 year from a mammogram with negative results compared with breast cancers detected by screening (hazard ratio, 1.92; 95% CI, 1.39-2.65). Higher breast cancer-specific mortality remained statistically significant for IBCs diagnosed within 1 year after adjusting for trial group, molecular subtype, waist to hip ratio, histologic characteristics, and either tumor size (hazard ratio, 1.46; 95% CI, 1.03-2.08) or lymph node involvement (hazard ratio, 1.44; 95% CI, 1.03-2.01). However, significance was lost when tumor size and lymph node involvement were both included in the model (hazard ratio, 1.34; 95% CI, 0.96-1.88). Interval breast cancers diagnosed between 1 and 2.5 years from a mammogram with negative results were not different from breast cancers detected by screening based on prognostic factors or mortality. Conclusions and Relevance: Women with IBCs diagnosed within 1 year of negative mammogram results overall were associated with worse survival than women with breast cancers detected by screening. These differences in survival may be due to a uniquely aggressive biology among IBC cases.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/mortalidade , Detecção Precoce de Câncer/estatística & dados numéricos , Idoso , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Estudos de Coortes , Feminino , Humanos , Mamografia/estatística & dados numéricos , Pessoa de Meia-Idade , Saúde da Mulher
10.
JCI Insight ; 5(13)2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-32497023

RESUMO

BACKGROUNDDysregulation of l-arginine metabolism has been proposed to occur in patients with severe asthma. The effects of l-arginine supplementation on l-arginine metabolite profiles in these patients are unknown. We hypothesized that individuals with severe asthma with low fractional exhaled nitric oxide (FeNO) would have fewer exacerbations with the addition of l-arginine to their standard asthma medications compared with placebo and would demonstrate the greatest changes in metabolite profiles.METHODSParticipants were enrolled in a single-center, crossover, double-blind l-arginine intervention trial at UCD. Subjects received placebo or l-arginine, dosed orally at 0.05 mg/kg (ideal body weight) twice daily. The primary end point was moderate asthma exacerbations. Longitudinal plasma metabolite levels were measured using mass spectrometry. A linear mixed-effect model with subject-specific intercepts was used for testing treatment effects.RESULTSA cohort of 50 subjects was included in the final analysis. l-Arginine did not significantly decrease asthma exacerbations in the overall cohort. Higher citrulline levels and a lower arginine availability index (AAI) were associated with higher FeNO (P = 0.005 and P = 2.51 × 10-9, respectively). Higher AAI was associated with lower exacerbation events. The eicosanoid prostaglandin H2 (PGH2) and Nα-acetyl-l-arginine were found to be good predictors for differentiating clinical responders and nonresponders.CONCLUSIONSThere was no statistically significant decrease in asthma exacerbations in the overall cohort with l-arginine intervention. PGH2, Nα-acetyl-l-arginine, and the AAI could serve as predictive biomarkers in future clinical trials that intervene in the arginine metabolome.TRIAL REGISTRATIONClinicalTrials.gov NCT01841281.FUNDINGThis study was supported by NIH grants R01HL105573, DK097154, UL1 TR001861, and K08HL114882. Metabolomics analysis was supported in part by a grant from the University of California Tobacco-Related Disease Research Program program (TRDRP).

11.
Acad Radiol ; 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32534966

RESUMO

RATIONALE AND OBJECTIVES: To establish a proof-of-principle for combined assessment of pulmonary ventilation and perfusion using single-energy computed tomography (CT) and image processing/analysis (denoted as single-energy CT ventilation/perfusion imaging). MATERIALS AND METHODS: Breath-hold CT scans were acquired at end-expiration and end-inspiration before injection of iodinated contrast agents, and repeated at end-inspiration after contrast injection for 17 canines (8 normal and 9 diseased lung subjects). Ventilation images were calculated with deformable image registration to map the end-expiratory and end-inspiratory CT images and quantitative analysis for regional volume changes as surrogates for ventilation. Perfusion images were calculated by subtracting the end-inspiratory precontrast CT from the deformably registered end-inspiratory postcontrast CT, yielding a map of regional Hounsfield unit enhancement as a surrogate for perfusion. Ventilation-perfusion matching, spatial heterogeneity, and gravitationally directed gradients were compared between two groups using a Wilcoxon rank-sum test. RESULTS: The normal group had significantly higher Dice similarity coefficients for spatial overlap of segmented functional volumes between ventilation and perfusion (median 0.40 vs. 0.33, p = 0.05), suggesting stronger ventilation-perfusion matching. The normal group also had greater Spearman's correlation coefficients based on 16 regions of interest (median 0.58 vs. 0.40, p = 0.09). The coefficients of variation were comparable (median, ventilation 0.71 vs. 0.91, p = 0.60; perfusion 0.63 vs. 0.75, p = 0.27). The linear regression slopes of gravitationally directed gradient were also comparable for ventilation (median, ventilation -0.26 vs. -0.18, p = 0.19; perfusion -0.17 vs. -0.06, p = 0.11). CONCLUSION: These findings provide proof-of-principle for single-energy CT ventilation/perfusion imaging.

12.
J Nanosci Nanotechnol ; 20(10): 6094-6102, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32384957

RESUMO

In this study, the insoluble drug, progesterone, was formulated into a progesterone nanocrystal injection to improve the saturation solubility, release rate, and efficacy of progesterone, as well as to increase the relative bioavailability of progesterone, reduce the subsequent irritation, and minimize the toxicity; the advantages and feasibility of the progesterone nanocrystalline injection in the prevention of premature delivery and protection against pregnancy-associated risks in pregnant females was evaluated. The wet grinding method was used to prepare the progesterone nanocrystalline injection; its morphology, particle size, and potential were characterized by transmission electron microscopy. Crystal structure was analyzed by X-ray powder diffraction; the solubility of the injection and the progesterone drug substance in water, and the In Vitro release of the drug were evaluated for its nanometer effect In Vitro. Rabbits were injected with the progesterone nanocrystal injection as well as commercially available progesterone injections for evaluation in vivo. The formulation process of a progesterone nanocrystal injection is feasible. The crystal form is stable and the particle size is uniform. Moreover, we found that it improves the release rate, saturation solubility, and bioavailability of progesterone, while reducing muscle irritation. The results have clinical research significance.

13.
Cancer Lett ; 483: 12-21, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32330514

RESUMO

Prostate cancer (PCa) is characterized by a unique dependence on optimal androgen receptor (AR) activity where physiological androgen concentrations induce proliferation but castrate and supraphysiological levels suppress growth. This feature has been exploited in bipolar androgen therapy (BAT) for castrate resistant malignancies. Here, we investigated the role of the tumor suppressor protein p14ARF in maintaining optimal AR activity and the function of the AR itself in regulating p14ARF levels. We used a tumor tissue array of differing stages and grades to define the relationships between these components and identified a strong positive correlation between p14ARF and AR expression. Mechanistic studies utilizing CWR22 xenograft and cell culture models revealed that a decrease in AR reduced p14ARF expression and deregulated E2F factors, which are linked to p14ARF and AR regulation. Chromatin immunoprecipitation studies identified AR binding sites upstream of p14ARF. p14ARF depletion enhanced AR-dependent PSA and TMPRSS2 transcription, hence p14ARF constrains AR activity. However, p14ARF depletion ultimately results in apoptosis. In PCa cells, AR co-ops p14ARF as part of a feedback mechanism to ensure optimal AR activity for maximal prostate cancer cell survival and proliferation.

14.
Am J Epidemiol ; 189(9): 972-981, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32314781

RESUMO

Dual-outcome intention-to-treat hazard rate analyses have potential to complement single-outcome analyses for the evaluation of treatments or exposures in relation to multivariate time-to-response outcomes. Here we consider pairs formed from important clinical outcomes to obtain further insight into influences of menopausal hormone therapy on chronic disease. As part of the Women's Health Initiative, randomized, placebo-controlled hormone therapy trials of conjugated equine estrogens (CEE) among posthysterectomy participants and of these same estrogens plus medroxyprogesterone acetate (MPA) among participants with an intact uterus were carried out at 40 US clinical centers (1993-2016). These data provide the context for analyses covering the trial intervention periods and a nearly 20-year (median) cumulative duration of follow-up. The rates of multiple outcome pairs were significantly influenced by hormone therapy, especially over cumulative follow-up, providing potential clinical and mechanistic insights. For example, among women randomized to either regimen, hazard ratios for pairs defined by fracture during intervention followed by death from any cause were reduced and hazard ratios for pairs defined by gallbladder disease followed by death were increased, though these findings may primarily reflect single-outcome associations. In comparison, hazard ratios for diabetes followed by death were reduced with CEE but not with CEE + MPA, and those for hypertension followed by death were increased with CEE + MPA but not with CEE.


Assuntos
Terapia de Reposição de Estrogênios , Ensaios Clínicos Controlados Aleatórios como Assunto , Idoso , Doenças Cardiovasculares/epidemiologia , Estrogênios Conjugados (USP)/administração & dosagem , Feminino , Fraturas Ósseas/epidemiologia , Doenças da Vesícula Biliar/epidemiologia , Humanos , Incidência , Análise de Intenção de Tratamento , Acetato de Medroxiprogesterona/administração & dosagem , Pessoa de Meia-Idade , Pós-Menopausa , Fatores de Risco , Estados Unidos/epidemiologia
16.
Nutrients ; 12(4)2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-32344738

RESUMO

Obesity is a rapidly growing public health threat in China. Improvement of dietary knowledge may potentially reduce the risk of obesity and being overweight. However, existing studies focus on measuring the mean effects of nutrition knowledge on body mass index (BMI). There is a lack of literature on the effect of dietary knowledge on BMI, and the potential heterogeneity of the effect across the whole BMI distribution and across socioeconomic status (SES) groups. This study aims to investigate the heterogeneous nature of the relationship between dietary knowledge, SES, and BMI, using data from the China Health and Nutrition Survey (CHNS) in 2015. We employed unconditional quantile regression (UQR) to assess how the relationship between dietary knowledge, SES, and BMI varies across the whole BMI distribution, and conducted subgroup analyses using different socio-economic subsamples. Results indicate that dietary knowledge had no statistically significant impact on BMI across the BMI distribution. There was a large degree of heterogeneity in the SES effect across the BMI distribution as well as a major gender difference in the SES effect on BMI. Education had a significant and inverse association with BMI across the BMI distribution, greater at higher BMI quantiles. Income growth had a larger effect on the 50th quantile of BMI for males in the middle-income group, but was not significant for females. As income increased, males without college educations had higher BMI while females with college or higher education generally had lower BMI. The findings of this study reveal the heterogeneous nature of the relationship between SES, gender, and obesity across the entire BMI distribution, suggesting that quantile regressions might offer a valuable framework for exploring the complex relationship of dietary knowledge, demographic, and socio-economic factors on obesity.

17.
Cancer Med ; 9(10): 3563-3573, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32207560

RESUMO

BACKGROUND: Body mass index (BMI) and diabetes are established risk factors for colorectal cancer (CRC), likely through perturbations in metabolic traits (e.g. insulin resistance and glucose homeostasis). Identification of interactions between variation in genes and these metabolic risk factors may identify novel biologic insights into CRC etiology. METHODS: To improve statistical power and interpretation for gene-environment interaction (G × E) testing, we tested genetic variants that regulate expression of a gene together for interaction with BMI (kg/m2 ) and diabetes on CRC risk among 26 017 cases and 20 692 controls. Each variant was weighted based on PrediXcan analysis of gene expression data from colon tissue generated in the Genotype-Tissue Expression Project for all genes with heritability ≥1%. We used a mixed-effects model to jointly measure the G × E interaction in a gene by partitioning the interactions into the predicted gene expression levels (fixed effects), and residual G × E effects (random effects). G × BMI analyses were stratified by sex as BMI-CRC associations differ by sex. We used false discovery rates to account for multiple comparisons and reported all results with FDR <0.2. RESULTS: Among 4839 genes tested, genetically predicted expressions of FOXA1 (P = 3.15 × 10-5 ), PSMC5 (P = 4.51 × 10-4 ) and CD33 (P = 2.71 × 10-4 ) modified the association of BMI on CRC risk for men; KIAA0753 (P = 2.29 × 10-5 ) and SCN1B (P = 2.76 × 10-4 ) modified the association of BMI on CRC risk for women; and PTPN2 modified the association between diabetes and CRC risk in both sexes (P = 2.31 × 10-5 ). CONCLUSIONS: Aggregating G × E interactions and incorporating functional information, we discovered novel genes that may interact with BMI and diabetes on CRC risk.

18.
Cancer Causes Control ; 31(5): 503-510, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32193704

RESUMO

INTRODUCTION: Evidence on the association between diabetes and risk of bladder cancer has been controversial. In addition, findings on the associations between duration of diabetes, diabetes treatment, and risk of bladder cancer have been inconsistent. METHODS: A total of 148,208 participants in Women's Health Initiative study were included. Information on diabetes status, diabetes duration, and treatment was collected both at baseline and during follow-up. Information on potential confounders including age, race/ethnicity, education, occupation, family history of cancer, smoking status, alcohol consumption, total physical activity, body mass index, and daily dietary intake were collected at baseline. Bladder cancer cases were collected and confirmed by a centralized review of pathology reports. Cox proportional hazard models with time-varying covariates were used to examine associations of diabetes status, duration of diabetes, and diabetes treatment with bladder cancer risk. RESULTS: During a median follow-up of 18.5 years, 865 bladder cancer cases were identified. There were no significant associations of diabetes, duration of diabetes, or diabetes treatment with risk of bladder cancer. Participants with prevalent diabetes did not have significantly higher risk of bladder cancer compared with those without diabetes. CONCLUSION: Diabetes was not significantly associated with risk of bladder cancer among postmenopausal women.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Pós-Menopausa , Neoplasias da Bexiga Urinária/epidemiologia , Idoso , Índice de Massa Corporal , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
20.
EClinicalMedicine ; 18: 100240, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31938786

RESUMO

Background: Meta-analyses of observational studies associate adherence to several dietary patterns with cognitive health. However, limited evidence from full scale, randomized controlled trials precludes causal inference regarding dietary effects on cognitive function. Methods: The Women's Health Initiative (WHI) Dietary Modification (DM) randomized trial, in 48,835 postmenopausal women, included a subset of 1,606 WHI Memory Study (WHIMS) participants >= 65 years old, to assess low-fat dietary pattern influence on global cognitive function, evaluated with annual screening (Modified Mini-Mental State Examinations [3MSE]). Participants were randomized by a computerized, permuted block algorithm, stratified by age group and center, to a dietary intervention (40%) to reduce fat intake to 20% of energy and increase fruit, vegetable and grain intake or usual diet comparison groups (60%). The study outcome was possible cognition impairment (failed cognitive function screening) through the 8.5 year (median) dietary intervention. Those failing screening received a comprehensive, multi-phase cognitive function assessment to classify as: no cognitive impairment, mild cognitive impairment, or probable dementia. Exploratory analyses examined the composite endpoint of death after possible cognitive impairment through 18.7 years (median) follow-up. The WHI trials are registered at ClinicalTrials.gov:NCT00000611. Findings: Among the 1,606 WHIMS participants, the dietary intervention statistically significantly reduced the incidence of possible cognitive impairment (n = 126; hazard ratio [HR] 0.59 95% confidence interval [CI] 0.38-0. 91, P = 0.01) with HR for dietary influence on subsequent mild cognitive impairment of 0.65 (95% CI 0.35-1.19) and HR of 0.63 (95% CI 0.19-2.10) for probable dementia (PD). Through 18.7 years, deaths from all-causes after possible cognitive impairment were non-significantly lower in the dietary intervention group (0.56% vs 0.77%, HR 0.83 95% CI 0.35 to 2.00, P = 0.16). Interpretation: Adoption of a low-fat eating pattern, representing dietary moderation, significantly reduced risk of possible cognitive impairment in postmenopausal women. Funding: Several Institutes of the US National Institutes of Health.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA