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Rationale, Design, and Implementation of Intensive Risk Factor Treatment in the CREST2 Trial.
Turan, TN, Voeks, JH, Chimowitz, MI, Roldan, A, LeMatty, T, Haley, W, Lopes-Virella, M, Chaturvedi, S, Jones, M, Heck, D, et al
Stroke. 2020;(10):2960-2971
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Abstract
BACKGROUND AND PURPOSE The CREST2 trial (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis) is comparing intensive medical management (IMM) alone to IMM plus revascularization with carotid endarterectomy or transfemoral carotid artery stenting for preventing stroke or death within 44 days after randomization or ipsilateral ischemic stroke thereafter. There are extensive clinical trial data on outcomes after revascularization of asymptomatic carotid stenosis, but not for IMM. As such, the experimental treatment in CREST2 is IMM, which is described in this article. METHODS IMM consists of aspirin 325 mg/day and intensive risk factor management, primarily targeting systolic blood pressure <130 mm Hg (initially systolic blood pressure <140 mm Hg) and LDL (low-density lipoprotein) cholesterol <70 mg/dL. Secondary risk factor targets focus on tobacco smoking, non-HDL (high-density lipoprotein), HbA1c (hemoglobin A1c), physical activity, and weight. Risk factor management is performed by site personnel and a lifestyle coaching program delivered by telephone. We report interim risk factor data on 1618 patients at baseline and last follow-up through 24 months. RESULTS The mean baseline LDL of 80.5 mg/dL improved to 66.7 mg/dL. The mean baseline systolic blood pressure of 139.7 mm Hg improved to 130.3 mm Hg. The proportion of patients in-target improved from 43% to 61% for systolic blood pressure <130 mm Hg and from 45% to 67% for LDL<70 mg/dL (both changes P<0.001). CONCLUSIONS The rigorous multimodal approach to intensive stroke risk factor management in CREST2 has resulted in significant improvements in risk factor control that will enable a comparison of cutting-edge medical care to revascularization in patients with asymptomatic carotid stenosis. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02089217.
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Impact of smoking status and concomitant medications on the effect of high-dose N-acetylcysteine on chronic obstructive pulmonary disease exacerbations: A post-hoc analysis of the PANTHEON study.
Papi, A, Zheng, J, Criner, GJ, Fabbri, LM, Calverley, PMA
Respiratory medicine. 2019;:37-43
Abstract
BACKGROUND N-acetylcysteine (NAC) 600 mg twice daily is a well-tolerated oral antioxidant mucolytic that reduces the risk of moderate to severe chronic obstructive pulmonary disease (COPD) exacerbations. PANTHEON was one of the largest studies to evaluate NAC in COPD. It recruited current, ex- and never-smokers, concomitantly treated with other medications, and used a symptom-based definition of COPD exacerbations rather than the conventional healthcare resource utilisation (HCU) criteria. METHODS This manuscript reports post-hoc analyses of the PANTHEON dataset investigating whether smoking status or use of concomitant medications influenced the efficacy of NAC in terms of reducing exacerbations, defined according to HCU. RESULTS Compared with placebo (N = 482), NAC (N = 482) reduced the rate of HCU events by 20% (p = 0.0027), with a larger effect in current/ex-smokers (23%; p < 0.01). In patients receiving NAC and long-acting inhaled bronchodilator(s) but no ICS, there was a 60% reduction in the rate of exacerbations compared to those receiving placebo, long-acting bronchodilator(s) and ICS (p < 0.0001). CONCLUSIONS Overall, these post-hoc hypothesis-generating analyses confirm that NAC reduces the rate of COPD exacerbations, particularly in patients with COPD who have a significant smoking history, and in those not treated with ICS. NAC may provide an alternative to ICS-containing combinations in these patient subgroups. CLINICAL TRIAL REGISTRATION Chinese Clinical Trials Registry, ChiCTR-TRC-09000460.
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Examining Associations between Perinatal and Postnatal Risk Factors for Childhood Obesity Using Sibling Comparisons.
Hawkins, SS, Baum, CF, Rifas-Shiman, SL, Oken, E, Taveras, EM
Childhood obesity (Print). 2019;(4):254-261
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Abstract
Background: One of the major criticisms of observational studies examining risk factors for childhood obesity is unmeasured confounding. We examined the associations between breastfeeding initiation, cesarean delivery, prenatal smoking, and gestational diabetes mellitus (GDM) with childhood obesity using both a traditional observational approach and a sibling-pair design with family fixed effects. Methods: We used data from the Linked the Collecting Electronic Nutrition Trajectory Data Using e-Records of Youth (CENTURY) Study, a clinical database created through the linkage of well-child visits with children's birth certificates, with obesity measured at 2 (N = 55,058) and 5 (N = 43,894) years of age. We conducted three sets of regression models: (1) full sample to examine the adjusted association between each risk factor and obesity with clustering by family; (2) rerun only among siblings with clustering by family; and (3) fixed effects analysis among siblings. Results: Across risk factors, 30%-39% of children had siblings. In the full sample, breastfeeding initiation was associated with a lower BMI z-score, while cesarean delivery and smoking during pregnancy were associated with a higher BMI z-score. Effect sizes were consistent in models with siblings only. However, in the fixed effects models, the coefficients attenuated and were no longer significant for each of these risk factors. We found no association between GDM and child BMI z-score in any of the models. Results were consistent for childhood obesity as a dichotomous measure and at 5 years of age. Conclusions: Our findings suggest that unmeasured genetic, environmental, and familial factors are likely confounding associations between breastfeeding, cesarean delivery, prenatal smoking, and GDM with childhood obesity in observational studies.
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Activated and Micronized Zeolite in the Modulation of Cellular Oxidative Stress in Mexican Smokers: A Randomized Clinical Trial.
Atitlán-Gil, A, Bretón-de la Loza, MM, Jiménez-Ortega, JC, Belefant-Miller, H, Betanzos-Cabrera, G
Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion. 2017;(3):146-151
Abstract
BACKGROUND Activated and micronized zeolites are used as detoxifying agents in humans. Detoxification is attributed to their ability to reduce lipid peroxidation by scavenging free radicals. OBJECTIVE To evaluate activated and micronized zeolites as modulators of cellular oxidative stress in Mexican smokers without lung diseases. METHODS Randomized clinical trial. Subjects were randomly divided into three groups: activated and micronized zeolites, n = 29; vitamin E, an accepted antioxidant, n = 29; and maltodextrin as control, n = 27. Each group received the corresponding supplementation, dissolved in water, once a day for 30 days as follows: activated and micronized zeolites, 5.4 g activated and micronized zeolite; vitamin E, 400 mg D-alpha tocopheryl acetate; and maltodextrin, 250 mg of maltodextrin. The thiobarbituric acid reactive substances assay was used to screen for lipid peroxidation. Catalase activity, plasma antioxidant capacity, and hydrogen peroxide levels were also measured. Results were analyzed by a one-way ANOVA and post hoc test of Bonferroni. RESULTS Subjects administered activated and micronized zeolites had equivalent antioxidant activities as subjects administered vitamin E. CONCLUSIONS Activated and micronized zeolites may be useful as a modulator of oxidative stress in smokers. However, inclusion of a comparison group of non-smokers would be useful in future studies to assess the degree to which zeolites reverse the oxidant stress.
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Prospective study of serum cysteine and cysteinylglycine and cancer of the head and neck, esophagus, and stomach in a cohort of male smokers.
Miranti, EH, Freedman, ND, Weinstein, SJ, Abnet, CC, Selhub, J, Murphy, G, Diaw, L, Männistö, S, Taylor, PR, Albanes, D, et al
The American journal of clinical nutrition. 2016;(3):686-93
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Abstract
BACKGROUND The nonessential amino acid cysteine is known to be involved in many antioxidant and anticarcinogenic pathways. Cysteinylglycine is a pro-oxidant metabolite of glutathione and a precursor of cysteine. OBJECTIVE To examine the relation between serum cysteine and cysteinylglycine and risk of gastric adenocarcinomas, esophageal squamous cell carcinomas, and head and neck squamous cell carcinomas, we conducted a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention study of male Finnish smokers aged 50-69 y at baseline. DESIGN In total, 170 gastric adenocarcinomas, 68 esophageal squamous cell carcinomas, and 270 head and neck squamous cell carcinomas (identified from the Finnish Cancer Registry) were matched one-to-one with cancer-free control subjects on age and the date of serum collection. We calculated ORs and 95% CIs with the use of a multivariate-adjusted conditional logistic regression. RESULTS Cysteine had a U-shaped association with gastric adenocarcinomas; a model that included a linear and a squared term had a significant global P-test (P = 0.036). Serum cysteinylglycine was inversely associated with adenocarcinomas of the gastric cardia (OR for above the median compared with below the median: 0.07; 95% CI: 0.01, 0.70; n = 38 cases) but not for other sites. Both cysteine and cysteinylglycine were not associated with esophageal squamous cell carcinoma or head and neck squamous cell carcinoma. CONCLUSIONS We observed associations between serum cysteine and cysteinylglycine with upper gastrointestinal cancer risk. Future studies are needed to replicate these findings. This trial was registered at clininicaltrials.gov as NCT00342992.
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Vitamin E and the risk of pneumonia: using the I 2 statistic to quantify heterogeneity within a controlled trial.
Hemilä, H
The British journal of nutrition. 2016;(9):1530-1536
Abstract
Analyses in nutritional epidemiology usually assume a uniform effect of a nutrient. Previously, four subgroups of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of Finnish male smokers aged 50-69 years were identified in which vitamin E supplementation either significantly increased or decreased the risk of pneumonia. The purpose of this present study was to quantify the level of true heterogeneity in the effect of vitamin E on pneumonia incidence using the I 2 statistic. The I 2 value estimates the percentage of total variation across studies that is explained by true differences in the treatment effect rather than by chance, with a range from 0 to 100 %. The I 2 statistic for the effect of vitamin E supplementation on pneumonia risk for five subgroups of the ATBC population was 89 % (95 % CI 78, 95 %), indicating that essentially all heterogeneity was true variation in vitamin E effect instead of chance variation. The I 2 statistic for heterogeneity in vitamin E effects on pneumonia risk was 92 % (95 % CI 80, 97 %) for three other ATBC subgroups defined by smoking level and leisure-time exercise level. Vitamin E decreased pneumonia risk by 69 % among participants who had the least exposure to smoking and exercised during leisure time (7·6 % of the ATBC participants), and vitamin E increased pneumonia risk by 68 % among those who had the highest exposure to smoking and did not exercise (22 % of the ATBC participants). These findings refute there being a uniform effect of vitamin E supplementation on the risk of pneumonia.
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A comparative analysis of predictors for 1-year recurrent acute coronary syndromes events, by age group: the Greek observational study of ACS (GREECS).
Panagiotakos, DB, Notara, V, Georgousopoulou, EN, Pitsavos, C, Antonoulas, A, Kogias, Y, Mantas, Y, Stravopodis, P, Zombolos, S, Stefanadis, C, et al
Maturitas. 2015;(2):205-11
Abstract
OBJECTIVES To evaluate the potential differences in risk factors' profile for in-hospital mortality and up to 1-year prognosis, between younger and older patients with first acute coronary syndromes (ACS). METHODS From October 2003 to September 2004, 1323 patients with first ACS event from 6 urban and rural Greek hospitals were enrolled into the study, classified as those < 65 years and ≥ 65 years old. Multiple logistic regression analysis was used to evaluate the association between socio-demographic, lifestyle, clinical characteristics and the disease prognosis for one year after discharge. RESULTS The men-to-women ratio was 8.5-to-1.5 for those < 65 years, whereas, it was 6.6-to-3.4 for those above 65 years (p < 0.001). In-hospital deaths and recurrent event within 30-days was higher among older patients (p < 0.001). After the period of 6-months, the event-rate was higher among the younger patients (p < 0.001). Current smoking was associated with increased risk of 1-month recurrent events, in patients < 65 years (p < 0.05). Myocardial infarction and history of diabetes were associated with increased risk in older patients (p < 0.1). CONCLUSION Age-specific identification of the risk factors for recurrent events may have important clinical and public health implications and lead to the development of more effective risk reduction strategies.
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Raw garlic consumption as a protective factor for lung cancer, a population-based case-control study in a Chinese population.
Jin, ZY, Wu, M, Han, RQ, Zhang, XF, Wang, XS, Liu, AM, Zhou, JY, Lu, QY, Zhang, ZF, Zhao, JK
Cancer prevention research (Philadelphia, Pa.). 2013;(7):711-8
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Protective effect of garlic on the development of cancer has been reported in the in vitro and in vivo experimental studies; however, few human epidemiologic studies have evaluated the relationship. A population-based case-control study has been conducted in a Chinese population from 2003 to 2010, with the aim to explore the association between raw garlic consumption and lung cancer. Epidemiologic data were collected by face-to-face interviews using a standard questionnaire among 1,424 lung cancer cases and 4,543 healthy controls. Unconditional logistic regression was used to estimate adjusted ORs and their 95% confidence intervals (CI), and to evaluate ratio of ORs (ROR) for multiplicative interactions between raw garlic consumption and other risk factors. After adjusting for potential confounding factors, raw garlic consumption of 2 times or more per week is inversely associated with lung cancer (OR = 0.56; 95% CI, 0.44-0.72) with a monotonic dose-response relationship (Ptrend < 0.001). Furthermore, strong interactions at either additive and/or multiplicative scales were observed between raw garlic consumption and tobacco smoking [synergy index (SI) = 0.70; 95% CI, 0.57-0.85; and ROR = 0.78; 95% CI, 0.67-0.90], as well as high-temperature cooking oil fume (ROR = 0.77; 95% CI, 0.59-1.00). In conclusion, protective association between intake of raw garlic and lung cancer has been observed with a dose-response pattern, suggesting that garlic may potentially serve as a chemopreventive agent for lung cancer. Effective components in garlic in lung cancer chemoprevention warrant further in-depth investigation.
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Acute (but not chronic) smoking paradoxically protects the endothelium from ischemia and reperfusion: insight into the "smoking paradox".
Lisi, M, Dragoni, S, Leone, MC, Münzel, T, Parker, JD, Gori, T
Clinical research in cardiology : official journal of the German Cardiac Society. 2013;(5):387-9
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Correlation of habits and clinical findings with histopathological diagnosis in oral submucosal fibrosis patients.
Ara, SA, Arora, V, Zakaullah, S, Raheel, SA, Rampure, P, Ashraf, S
Asian Pacific journal of cancer prevention : APJCP. 2013;(12):7075-80
Abstract
BACKGROUND Oral submucosal fibrosis (OSMF) is one of the most prevalent premalignant conditions in India which is easy to diagnose but difficult to manage. At present it is considered as irreversible and incurable. It has also been referred to as an epidemic in India. AIMS AND OBJECTIVES To correlate the frequency and duration of habits with clinical staging, functional staging and histopathological grading and to correlate the clinical and functional staging with histopathological grading. MATERIALS AND METHODS The study included a total of 90 subjects, 80 with OSMF in the experimental group and 10 patients in the control group. Patient personal history was recorded with chewing habits, including frequency and duration of chewing. The site of keeping the quid, time duration and whether he/she swallows it or spits it were also noted. Clinical staging was done on the presence of palpable fibrous bands. Functional staging was accomplished by measuring mouth opening. Incisional biopsy was done for all the patients for histopathological examination. Histopathological grading was according to Pindborg and Sirsat. RESULTS The experimental group comprised 71 males and 9 females, the majority of which were in the age group of 21-30 years. Correlation of habits with clinical staging, functional staging and histopathological grading were significant (p<0.05). Clinical and functional staging did not correlate with histopathological grading, but the correlation of clinical and functional staging was highly significant (p<0.01). CONCLUSIONS The widespread habit of chewing gutkha is a major risk factor for OSMF, especially in the younger age group. In this study, it was found that with increase in the duration and frequency of the habit the severity of the disease increased.