Sleep disturbances, chronotype and social jetlag (SJL) have been associated with increased risks for major chronic diseases that take decades to develop, such as obesity, metabolic syndrome and ...cardiovascular disease. Potential relationships between poor sleep, chronotype and SJL as they relate to metabolic risk factors for chronic disease have not been extensively investigated. This prospective study examined chronotype, SJL and poor sleep in relation to both obesity and elevated blood pressure among healthy young adults. SJL and objective sleep measures (total sleep time, sleep onset latency, wake after sleep onset and sleep efficiency) were derived from personal rest/activity monitoring (armband actigraphy) among 390 healthy adults 21-35 years old. Participants wore the device for 6-10 days at 6-month intervals over a 2-year period (n = 1431 repeated observations). Chronotypes were categorized into morning, intermediate and evening groups using repeated measures latent class analysis. Means of SJL and sleep measures among latent chronotype groups were compared using partial F-tests in generalized linear mixed models. Generalized linear mixed models also were used to generate odds ratios (ORs) with 95% confidence intervals (CIs) examining the relationship between repeated measures of chronotype, SJL, sleep and concurrent anthropometric outcome measures (body mass index, percentage of body fat, waist-to-hip ratio, waist-to-height ratio), systolic blood pressure and diastolic blood pressure. Sleep latency ≥12 min was associated with increased odds of a high waist-to-height ratio (OR = 1.37; CI: 1.03-1.84). Neither chronotype nor SJL was independently associated with anthropometric outcomes or with blood pressure. Relationships between poor sleep and anthropometric outcomes or blood pressure varied by chronotype. Morning types with total sleep time <6 h, sleep efficiency <85% or wake after sleep onset ≥60 min were more likely to have an increased percentage of body fat, waist-to-hip ratio and waist-to-height ratio relative to those with an intermediate chronotype. Similarly, sleep latency ≥12 min was associated with increased odds of elevated systolic blood pressure (OR = 1.90; CI: 1.15-3.16, p
= 0.02) among morning versus intermediate chronotypes. No relationships between poor sleep and obesity or elevated blood pressure were observed among evening chronotypes. The results from this study among healthy young adults suggest that poor sleep among morning types may be more strongly associated with obesity and elevated blood pressure relative to those with an intermediate (neutral) chronotype. Sleep-related metabolic alterations among different chronotypes warrant further investigation.
Although levels of physical activity and aerobic capacity decline with age and the prevalence of obesity tends to increase with age, the independent and joint associations among fitness, adiposity, ...and mortality in older adults have not been adequately examined.
To determine the association among cardiorespiratory fitness ("fitness"), adiposity, and mortality in older adults.
Cohort of 2603 adults aged 60 years or older (mean age, 64.4 SD, 4.8 years; 19.8% women) enrolled in the Aerobics Center Longitudinal Study who completed a baseline health examination during 1979-2001. Fitness was assessed by a maximal exercise test, and adiposity was assessed by body mass index (BMI), waist circumference, and percent body fat. Low fitness was defined as the lowest fifth of the sex-specific distribution of maximal treadmill exercise test duration. The distributions of BMI, waist circumference, and percent body fat were grouped for analysis according to clinical guidelines.
All-cause mortality through December 31, 2003.
There were 450 deaths during a mean follow-up of 12 years and 31 236 person-years of exposure. Death rates per 1000 person-years, adjusted for age, sex, and examination year were 13.9, 13.3, 18.3, and 31.8 across BMI groups of 18.5-24.9, 25.0-29.9, 30.0-34.9, and > or =35.0, respectively (P = .01 for trend); 13.3 and 18.2 for normal and high waist circumference (> or =88 cm in women; > or =102 cm in men) (P = .004); 13.7 and 14.6 for normal and high percent body fat (> or =30% in women; > or =25% in men) (P = .51); and 32.6, 16.6, 12.8, 12.3, and 8.1 across incremental fifths of fitness (P < .001 for trend). The association between waist circumference and mortality persisted after further adjustment for smoking, baseline health status, and BMI (P = .02) but not after additional adjustment for fitness (P = .86). Fitness predicted mortality risk after further adjustment for smoking, baseline health, and either BMI, waist circumference, or percent body fat (P < .001 for trend).
In this study population, fitness was a significant mortality predictor in older adults, independent of overall or abdominal adiposity. Clinicians should consider the importance of preserving functional capacity by recommending regular physical activity for older individuals, normal-weight and overweight alike.
Despite limited and conflicting evidence, hydroxychloroquine, alone or in combination with azithromycin, is widely used in COVID-19 therapy.
We performed a retrospective study of electronic health ...records of patients hospitalized with confirmed SARS-CoV-2 infection in US Veterans Health Administration medical centers between March 9, 2020 and April 29, 2020. Patients hospitalized within 24 h of diagnosis were classified based on their exposure to hydroxychloroquine alone (HC) or with azithromycin (HC+AZ) or no HC as treatments. The primary outcomes were mortality and use of mechanical ventilation.
A total of 807 patients were evaluated. Compared to the no HC group, after propensity score adjustment for clinical characteristics, the risk of death from any cause was higher in the HC group (adjusted hazard ratio aHR, 1.83; 95% confidence interval CI, 1.16-2.89; p = 0.009), but not in the HC+AZ group (aHR, 1.31; 95% CI, 0.80-2.15; p = 0.28). Both the propensity-score-adjusted risks of mechanical ventilation and death after mechanical ventilation were not significantly different in the HC group (aHR, 1.19; 95% CI, 0.78-1.82; p = 0.42 and aHR, 2.11; 95% CI, 0.96-4.62; p = 0.06, respectively) or in the HC+AZ group (aHR, 1.09; 95% CI, 0.72-1.66; p = 0.69 and aHR, 1.25; 95% CI, 0.59-2.68; p = 0.56, respectively) compared to the no HC group.
Among patients hospitalized with COVID-19, this retrospective study did not identify any significant reduction in mortality or in the need for mechanical ventilation with hydroxychloroquine treatment with or without azithromycin.
University of Virginia Strategic Investment Fund.
Abstract Background Evidence on the effect of cardiorespiratory fitness (CRF) on age-related longitudinal changes of lipids and lipoproteins is scarce. Objectives This study sought to assess the ...longitudinal aging trajectory of lipids and lipoproteins for the life course in adults and to determine whether CRF modifies the age-associated trajectory of lipids and lipoproteins. Methods Data came from 11,418 men, 20 to 90 years of age, without known high cholesterol, high triglycerides, cardiovascular disease, and cancer at baseline and during follow-up from the Aerobics Center Longitudinal Study. There were 43,821 observations spanning 2 to 25 health examinations (mean 3.5 examinations) between 1970 and 2006. CRF was quantified by a maximal treadmill exercise test. Marginal models using generalized estimating equations were applied. Results Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides, and non–high-density lipoprotein cholesterol (non–HDL-C) presented similar inverted U-shaped quadratic trajectories with aging: gradual increases were noted until age mid-40s to early 50s, with subsequent declines (all p < 0.0001). Compared with men with higher CRF, those with lower CRF developed abnormal values earlier in life: TC (≥200 mg/dl), LDL-C (≥130 mg/dl), non–HDL-C (≥160 mg/dl), and triglycerides/HDL-C ratio (≥3.0). Notably, abnormal values for TC and LDL-C in men with low CRF were observed around 15 years earlier than in those with high CRF. After adjusting for time-varying covariates, a significant interaction was found between age and CRF in each trajectory, indicating that CRF was more strongly associated with the aging trajectories of lipids and lipoproteins in young to middle-age men than in older men. Conclusions Our investigation reveals a differential trajectory of lipids and lipoproteins with aging according to CRF in healthy men and suggests that promoting increased CRF levels may help delay the development of dyslipidemia.
Abstract Background Failure of physiologic transformation of spiral arteries has been reported in preeclampsia, fetal growth restriction, fetal death, and spontaneous preterm labor with intact or ...ruptured membranes. Spiral arteries with failure of physiologic transformation are prone to develop atherosclerotic-like lesions of atherosis. There are striking parallels between preeclampsia and atherosclerotic disease, and between lesions of atherosis and atherosclerosis. Endothelial activation, identified by intercellular adhesion molecule-1 (ICAM-1) expression, is present in atherosclerotic-like lesions of heart transplantation, and is considered a manifestation of rejection. Similarly, endothelial activation/dysfunction has been implicated in the pathophysiology of atherosclerosis and preeclampsia. ICAM-1-overexpressing activated endothelial cells are more resistant to trophoblast displacement than non-activated endothelium, and may contribute to shallow spiral artery trophoblastic invasion in obstetrical syndromes having failure of physiologic transformation. Objective To determine whether failure of spiral artery physiologic transformation was associated with activation of interstitial extravillous trophoblasts and/or spiral artery endothelium and presence of acute atherosis in the placental basal plate. Study Design A cross-sectional study of 123 placentas (19 to 42 weeks gestation) obtained from normal pregnancies (n = 22), preterm prelabor rupture of membranes (n = 26), preterm labor (n = 23), preeclampsia (n = 27), intrauterine fetal death (n = 15) and small for gestational age (n = 10), was performed. Failure of spiral artery physiologic transformation and presence of cell activation was determined using immunohistochemistry of placental basal plates containing a median of 4 (minimum: 1; maximum: 9) vessels per placenta. Endothelial/trophoblast cell activation was defined by the expression of ICAM-1. Investigators examining microscopic sections were blinded to clinical diagnosis. Pairwise comparisons among placenta groups were performed with Fisher's exact test and Wilcoxon rank sum test using a Bonferroni-adjusted level of significance (0.025). Results We found that 87% (94/108) of placentas having spiral arteries with failure of physiologic transformation ( actin-positive and cytokeratin-negative) in the basal plate, and 0% (0/15) of placentas having only spiral arteries with complete physiologic transformation ( cytokeratin-positive and actin-negative), had arterial endothelial and/or interstitial extravillous trophoblasts reactive with the ICAM-1 activation marker ( P < 0.001). A significant correlation (R2 = 0.84) was found between expression of spiral artery endothelial and interstitial extravillous trophoblast ICAM-1 ( P < 0.001) in activated placentas. Lesions of atherosis were found in 31.9% (30/94) of placentas with complete and/or partial failure of physiologic transformation of spiral arteries ICAM-1-positive, in none of the 14 placentas with failure of physiologic transformation ICAM-1-negative, and in none of the 15 placentas with complete spiral artery physiologic transformation without failure ( P = 0.001). All placentas (30/30, 100%) with atherosis were identified in placentas having concomitant spiral artery endothelial and interstitial extravillous trophoblast activation. Conclusion Failure of spiral artery physiologic transformation in the placental basal plate is associated with interstitial extravillous trophoblast and arterial endothelial activation along with increased frequency of spiral artery atherosis. These findings may be used to improve the characterization of different disorders of the placental bed such as in refining the existing tools for the early prediction of risk for preterm, preeclamptic and other abnormal pregnancies.
Overdispersion is a problem encountered in the analysis of count data that can lead to invalid inference if unaddressed. Decision about whether data are overdispersed is often reached by checking ...whether the ratio of the Pearson chi-square statistic to its degrees of freedom is greater than one; however, there is currently no fixed threshold for declaring the need for statistical intervention. We consider simulated cross-sectional and longitudinal datasets containing varying magnitudes of overdispersion caused by outliers or zero inflation, as well as real datasets, to determine an appropriate threshold value of this statistic which indicates when overdispersion should be addressed.
In June 2012, Canada implemented new pictorial warnings on cigarette packages, along with package inserts with messages to promote response efficacy (i.e., perceived quitting benefits) and ...self-efficacy (i.e., confidence to quit). This study assessed smokers' attention toward warnings and inserts and its relationship with efficacy beliefs, risk perceptions and cessation at follow-up.
Data were analyzed in 2015 from a prospective online consumer panel of adult Canadian smokers surveyed every four months between September 2012 and September 2014. Generalized Estimating Equation models were estimated to assess associations between reading inserts, reading warnings and efficacy beliefs (self-efficacy, response efficacy), risk perceptions, quit attempts of any length, and sustained quit attempts (i.e., 30days or more) at follow-up. Models adjusted for socio-demographics, smoking-related variables, and time-in-sample effects.
Over the study period, reading warnings significantly decreased (p<0.0001) while reading inserts increased (p=0.004). More frequent reading of warnings was associated independently with stronger response efficacy (Boften/very often vs never=0.28, 95% CI: 0.11–0.46) and risk perceptions at follow-up (Boften/very often vs never=0.31, 95% CI: 0.06–0.56). More frequent reading of inserts was associated independently with stronger self-efficacy to quit at follow-up (Btwice or more vs none=0.30, 95% CI: 0.14–0.47), quit attempts (ORtwice or more vs none=1.68, 95% CI: 1.28–2.19), and sustained quit attempts (ORtwice or more vs none=1.48, 95% CI: 1.01–2.17).
More frequent reading of inserts was associated with self-efficacy to quit, quit attempts, and sustained quitting at follow-up, suggesting that inserts complement pictorial HWLs.
•Reading cigarette pack warnings decreased and reading inserts increased over time.•Reading warnings was associated with stronger response efficacy at follow up.•Reading inserts was associated with stronger self-efficacy to quit at follow up.•Reading inserts was independently associated with attempting to quit at follow up.•Reading inserts was associated with quitting for 30days or more at follow up.
Objective To assess whether exposure to movie smoking is associated with cigarette smoking among Argentinian adolescents. Study design A school-based longitudinal study involving 33 secondary schools ...in Argentina was performed. The sample included 2502 never smokers (average age at entry = 12.5 years), 1700 (67.9%) of whom completed follow-up surveys 17 months later. Exposure to the top 100 highest-grossing films for each year between 2009 and 2013 was assessed by content-coding films for tobacco and then by asking adolescents whether they had seen each of 50 titles, randomly selected from the larger pool, then parsing exposure into tertiles. Logistic regression models estimated aOR for the following transitions: nonsusceptible to susceptible never smoker, never smoker to ever smoker, and never smoker to current smoking (last 30 days). Results At follow-up, 34.4% of nonsusceptible never smokers became susceptible, 24.1% reported having tried smoking, and 9.4% were current smokers. Most exposure to movie smoking was from US-produced films (average 60.3 minutes compared with only 3.4 minutes from Argentine films). Greater exposure to smoking in movies was significantly associated with increased odds of becoming susceptible (aORfirst vs third tertile 1.77, 95% CI 1.30-2.41), of trying smoking (aORfirst vs third tertile 1.54, 1.14-2.08), and marginally associated with current smoking (AORfirst vs third tertile 1.54, 0.99-2.40). Exposure to smoking in US- or Argentine-produced films had similar associations. Conclusion In Argentina, exposure to smoking in the movies predicted future smoking transitions among early adolescents, with most exposure coming from viewing US movies.
We present motivation and new Stata commands for modeling count data. While the focus of this article is on modeling data with underdispersion, the new command for fitting generalized Poisson ...regression models is also suitable as an alternative to negative binomial regression for overdispersed data.
Physical activity may protect against breast cancer. Few prospective studies have evaluated breast cancer mortality in relation to cardiorespiratory fitness (CRF), an objective marker of physiologic ...response to physical activity habits.
We examined the association between CRF and risk of death from breast cancer in the Aerobics Center Longitudinal Study. Women (N = 14,811), aged 20 to 83 yr with no prior breast cancer history, received a preventive medical examination at the Cooper Clinic in Dallas, Texas, between 1970 and 2001. Mortality surveillance was completed through December 31, 2003. CRF was quantified as maximal treadmill exercise test duration and was categorized for analysis as low (lowest 20% of exercise duration), moderate (middle 40%), and high (upper 40%). At baseline, all participants were able to complete the exercise test to at least 85% of their age-predicted maximal heart rate.
A total of 68 breast cancer deaths occurred during follow-up (mean = 16 yr). Age-adjusted breast cancer mortality rates per 10,000 woman-years were 4.4, 3.2, and 1.8 for low, moderate, and high CRF groups, respectively (trend P = 0.008). After further controlling for body mass index, smoking, drinking, chronic conditions, abnormal exercise ECG responses, family history of breast cancer, oral contraceptive use, and estrogen use, hazard ratios (95% CI) for breast cancer mortality across incremental CRF categories were 1.00 (referent), 0.67 (0.35-1.26), and 0.45 (0.22-0.95) (trend P = 0.04).
These results indicate that CRF is associated with a reduced risk of dying from breast cancer in women.
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