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Many studies have examined the effects of meditation practice focused on the normal breath on vagal tone with mixed results. Heart Rhythm Meditation (HRM) is a unique meditation form that engages in the deep slow full breath, and puts the focus of attention on the heart. This form of breathing likely stimulates the vagus nerve with greater intensity. The purpose of this study was (a) to examine how the practice of HRM affects vagal activity as measured by heart rate variability (HRV); and (b) to examine how it affects participants' well-being. 74 participants signed consent agreeing to: (a) take a six-week course to learn the practice of HRM; (b) engage in a daily practice for 10 weeks; (c) have their heart rate variability read through ECG technology and to take two validated well-being instruments at the beginning and end of the 10 weeks; and (d) participate in a focus group interview examining their perceptions of how the practice affected their well-being. 48 participants completed the study. Quantitative findings show the effect of the practice of HRM approached significance for multiple measures of HRV and vagal tone. An increase in well-being scores for those who did the meditation more than 10-minutes per day did meet statistical significance. Qualitative data indicate: (a) the positive effects of HRM on stress and well-being; (b) the development of a more expanded sense of self; and (c) an increased awareness of the interconnection of the body-heart-emotions and HRM's role in emotion regulation. [ABSTRACT FROM AUTHOR]

Background The association between angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and severe acute respiratory syndrome coronavirus 2 susceptibility, particularly via ACE-2 receptor upregulation in the kidneys, raises concerns about potential kidney disease risks in long coronavirus disease (COVID) patients. This study explores the association of ACEI/ARB therapy on acute kidney injury (AKI), chronic kidney disease (CKD) and all-cause mortality in patients with and without long COVID. Methods A retrospective cohort study using TriNetX datasets was conducted, with diagnoses of long COVID via International Classification of Diseases, Tenth Revision (ICD-10) codes and prescription for ACEI/ARB as the classification of four cohorts: long COVID ACEI/ARB users (LCAUs), long COVID ACEI/ARB non-users (LCANs), non-long COVID ACEI/ARB users (NLCAUs) and non-long COVID ACEI/ARB non-users (NLCANs). Multivariable stratified Cox proportional hazards regression models assessed the adjusted hazard ratios (aHRs) across groups. Additional analyses were conducted, including time-dependent exposure analysis and comparison with an active comparator, calcium channel blockers. Results Our study included 18 168 long COVID and 181 680 propensity score-matched non-long COVID patients from October 2021 to October 2023. ACEI/ARB use did not significantly affect the risk of AKI or CKD when comparing LCAUs with LCANs and NLCAUs with NLCANs. However, a protective effect against all-cause mortality was observed {aHR 0.79 [95% confidence interval (CI) 0.65–0.93]} in the NLCAU group compared with the NLCAN group. Conversely, long COVID was associated with increased risks of CKD [aHR 1.49 (95% CI 1.03–2.14)] and all-cause mortality [aHR 1.49 (95% CI 1.00–2.23)] when comparing LCANs with NLCANs. The additional analyses support the primary findings. Conclusions ACEI/ARB treatment does not increase the incidence of CKD or AKI, regardless of long COVID status. However, long COVID itself is associated with increasing risks of kidney diseases and all-cause mortality. [ABSTRACT FROM AUTHOR]

BACKGROUND: Many approaches to quantifying air pollution exposures have been developed. However, the impact of choice of approach on air pollution estimates and health-effects associations remains unclear. OBJECTIVES: Our objective is to compare particulate matter with aerodynamic diameter ≤2.5 μm (PM2.5) concentrations and resulting health effects associations using multiple estimation approaches previously used in epidemiologic analyses. METHODS: We assigned annual PM2.5 exposure estimates from 1999 to 2004 derived from 11 different approaches to Women’s Health Initiative Memory Study (WHIMS) participant addresses within the contiguous US. Approaches included geostatistical interpolation approaches, land-use regression or spatiotemporal models, satellite-derived approaches, air dispersion and chemical transport models, and hybrid models. We used descriptive statistics and plots to assess relative and absolute agreement among exposure estimates and examined the impact of approach on associations between PM2.5 and death due to natural causes, cardiovascular disease (CVD) mortality, and incident CVD events, adjusting for individual-level covariates and climate-based region. RESULTS: With a few exceptions, relative agreement of approach-specific PM2.5 exposure estimates was high for PM2.5 concentrations across the contiguous US. Agreement among approach-specific exposure estimates was stronger near PM2.5 monitors, in certain regions of the country, and in 2004 vs. 1999. Collectively, our results suggest but do not quantify lower agreement at local spatial scales for PM2.5. There was no evidence of large differences in health effects associations with PM2.5 among estimation approaches in analyses adjusted for climate region. CONCLUSIONS: Different estimation approaches produced similar spatial patterns of PM2.5 concentrations across the contiguous US and in areas with dense monitoring data, and PM2.5-health effects associations were similar among estimation approaches. PM2.5 estimates and PM2.5-health effects associations may differ more in samples drawn from smaller areas or areas without substantial monitoring data, or in analyses with finer adjustment for participant location. Our results can inform decisions about PM2.5 estimation approach in epidemiologic studies, as investigators balance concerns about bias, efficiency, and resource allocation. Future work is needed to understand whether these conclusions also apply in the context of other air pollutants of interest [ABSTRACT FROM AUTHOR]

Objective: Identifying whether certain groups of people experience elevated rates or severities of psychiatric symptoms provides information to guide healthcare allocation. People living in urban areas have higher rates of some psychiatric disorders relative to people living in rural settings, however, it is unclear if psychiatric severity is more elevated in urban vs. rural settings. This study investigates the urban vs. rural differences in rates of psychiatric disorders and severity of psychiatric symptoms. Method: A cohort of patients (63% women, 85% White) presenting to an outpatient psychiatric treatment center in the U.S. completed patient-reported outcomes at all clinic visits as part of standard care. Rurality was determined by municipality population density. Sociodemographic characteristics, psychiatric diagnoses, trauma exposure, psychiatric symptom severity, functioning, and suicidality were compared by rural vs. urban municipality. Results: There were virtually no differences between patients living in rural vs. urban municipalities on rates of psychiatric disorders, severity of psychiatric symptoms, functional impairment, and suicidality (ps≥.09). The only difference was that patients living in rural municipalities had higher exposure to serious accidents than patients living in urban municipalities (p <.01); exposure to nine other traumatic events did not differ between groups (p≥.07). Conclusions: People living in urban and rural municipalities have a similar need for mental health treatment. Access to care may be one explanatory factor for the occasional rural-urban differences in rates of psychiatric disorders. In other words, if people living in rural areas can access care, their symptom presentations appear unlikely to differ from those of people living in urban areas. [ABSTRACT FROM AUTHOR]

Background: Measurement-based care has been called for as best practice in psychiatric care and learning health systems and use of transdiagnostic measures was suggested as part of the DSM-5. Our objective is to examine gender differences in first visit socioeconomic, transdiagnostic, and functional characteristics of a dynamic, real-world measurement-based care cohort. Methods: Transdiagnostic, functional, and clinical measures were collected from 3,556 patients at first visit in an ambulatory psychiatric clinic. All patients were evaluated at the first visit by board-certified psychiatrists or licensed clinical psychologists. Demographic variables and clinical diagnoses were collected from the Electronic Medical Record. Self-report measures were collected that assessed transdiagnostic symptoms (DSM-5 Level 1 Cross-cutting Measure and Level 2 symptom scales), disability, alcohol use, attention deficit hyperactivity disorder (ADHD) symptoms, depression, anxiety, mania, suicidal thoughts and behaviors, and trauma exposure. Results: Men and women did not differ in age, BMI, household income, high school graduation rate, race, or ethnicity, but women were more likely to be formerly married and less likely to have commercial insurance. Compared to men, women reported significantly higher overall psychopathology on the transdiagnostic Level 1 Cross-cutting measure and had higher depression, anxiety, sleep, anger, ADHD combined presentation, and suicidality severity. Women also had higher disability scores than men. However, men reported higher alcohol, tobacco and substance use, and more risky behavior than women. Trauma exposure differed significantly by gender; men reported more exposure to accidents, war-related trauma, serious accidents, and major disasters and women reported more unwanted sexual contact. Conclusions: This cross-sectional study of a transdiagnostic, ecologically-valid real-word measurement-based care cohort demonstrates gender differences in socioeconomic factors, trauma exposure, transdiagnostic symptoms, and functioning. [ABSTRACT FROM AUTHOR]

Introduction: The onset of puberty is associated with a shift in the circadian timing of sleep, leading to delayed sleep initiation [i.e., later sleep onset time (SOT)] due to later bedtimes and/or longer sleep onset latency (SOL). Several genome-wide association studies (GWAS) have identified genes that may be involved in the etiology of sleep phenotypes. However, circadian rhythms are also epigenetically regulated; therefore, epigenetic biomarkers may provide insight into the physiology of the pubertal sleep onset shift and the pathophysiology of prolonged or delayed sleep initiation. Results: The gene-wide analysis indicated differential methylation within or around 1818 unique genes across the sleep initiation measurements using self-report, actigraphy (ACT), and polysomnography (PSG), while GWAS-informed analysis yielded 67 genes. Gene hits were identified for bedtime (PSG), SOL (subjective, ACT and PSG) and SOT (subjective and PSG). DNA methylation within 12 genes was associated with both subjective and PSG-measured SOL, 31 with both ACT- and PSG-measured SOL, 19 with both subjective and ACT-measured SOL, and one gene (SMG1P2) had methylation sites associated with subjective, ACT- and PSG-measured SOL. Conclusions: Objective and subjective sleep initiation in adolescents is associated with altered DNA methylation in genes previously identified in adult GWAS of sleep and circadian phenotypes. Additionally, our data provide evidence for a potential epigenetic link between habitual (subjective and ACT) SOL and in-lab SOT and DNA methylation in and around genes involved in circadian regulation (i.e., RASD1, RAI1), cardiometabolic disorders (i.e., FADS1, WNK1, SLC5A6), and neuropsychiatric disorders (i.e., PRR7, SDK1, FAM172A). If validated, these sites may provide valuable targets for early detection and prevention of disorders involving prolonged or delayed SOT, such as insomnia, delayed sleep phase, and their comorbidity. [ABSTRACT FROM AUTHOR]

Background: A high comorbidity between attention‐deficit/hyperactivity disorder (ADHD) and obstructive sleep apnea (OSA) as well as similar impairments across neurobehavioral outcomes has been described in children. However, there is a paucity of research examining the comorbidity of these two disorders in adolescents. This study examined the association of OSA with sleep, neurobehavioral, and cardiometabolic outcomes in adolescents with ADHD from the general population. Methods: 421 adolescents (16.9 ± 2.3 years, 53.9% male) underwent 9‐hr polysomnography, neurobehavioral, and physical evaluation. ADHD was ascertained by a parent‐or‐self‐report of a lifetime diagnosis/treatment of ADHD. OSA was defined as an apnea hypopnea index of ≥2 events/hour. Groups of controls (n = 208), OSA‐alone (n = 115), ADHD‐alone (n = 54), and ADHD+OSA (n = 44) were studied. Multivariable‐adjusted general linear models tested group differences in PSG parameters, neurobehavioral, and cardiometabolic outcomes after controlling for sex, race/ethnicity, age, and/or body mass index percentile. Results: The ADHD+OSA group had significantly longer sleep onset latency, shorter total sleep time, lower sleep efficiency, and higher percent of stage 1 sleep, as compared with all other groups, however, these differences were diminished by excluding adolescents on psychoactive medication. The ADHD‐alone group showed significantly higher periodic limb movements than controls. The ADHD+OSA and ADHD‐alone groups did not significantly differ on any measure of neurocognitive or behavioral functioning. The ADHD+OSA and OSA‐alone groups showed significantly worse cardiometabolic and inflammatory biomarkers when compared to controls or the ADHD‐alone, but did not significantly differ between each other. Conclusions: Adolescents with a diagnosis ADHD+OSA showed phenotypic risk factors for OSA (i.e., overweight/obesity, visceral adiposity, metabolic syndrome, and inflammation) but not worse neurobehavioral outcomes when compared with ADHD‐alone. While comorbidity is possible, these data support that adolescents with a suspicion of ADHD should be screened for OSA, before a diagnosis is reached and psychoactive medication initiated. [ABSTRACT FROM AUTHOR]

Background: Diagnostic delay contributes to morbidity in psychiatric disorders. Methods: Patients in an ambulatory psychiatry clinic were given patient‐reported outcome measures at an initial visit, and a subset (N = 493) were given a structured interview (MINI International Neuropsychiatric Interview, MINI), in addition to the clinical encounter (CLIN). Diagnostic agreement between MINI and CLIN was assessed at an initial and follow‐up visit. Diagnostic delay was identified if diagnostic disagreement between MINI and CLIN occurred at the initial visit and changed to an agreement at a follow‐up visit. Registry data was compiled by an honest broker. Results: Significant agreement occurred between MINI and CLIN diagnoses for major depressive disorder (MDD), bipolar disorder (BD), generalized anxiety disorder, and panic disorder. Diagnostic agreement for MDD occurred at initial visit for 63% of patients, and at follow‐up for 87% of those with initial diagnostic disagreement; for BD, 75% at initial visit and 28% at follow‐up. No demographic, socioeconomic, symptom severity or functioning measures predicted diagnostic agreement for the MDD group at the first visit, however initial psychopathological symptom complexity predicted diagnostic agreement in the diagnostic delay group. Initial diagnostic agreement for BD was predicted by lower symptom burden and better social, physical, and occupational functioning. No factors predicted additional diagnostic agreement at the second visit in the diagnostic delay group. Conclusion: Initial assessment by a structured interview aided physicians in identifying MDD by the second visit in patients with complex psychopathology. Patients with high complexity/severity of symptoms and more difficulty with functioning were less commonly identified with BD even with the assistance of a structured interview. Use of structured assessment tools may improve the detection of psychiatric illness by clinicians at the first visit. [ABSTRACT FROM AUTHOR]

Objective: To identify countries in sub-Saharan Africa (SSA) that have not yet achieved at least 90 % universal salt iodization and factors associated with the consumption of non-iodized salt among women of reproductive age.Design: A cross-sectional study using data from Demographic and Health Surveys (DHS). The presence of iodine in household salt (iodized or non-iodized), which was tested during the survey process, was the study outcome. Multivariable logistic regression models were used to determine independent factors associated with the consumption of non-iodized salt among women of reproductive age.Setting: There were eleven countries in SSA that participated in the DHS since 2015 and measured the presence of iodine in household salt.Participants: Women (n 108 318) aged 15-49 years.Results: Countries with the highest rate of non-iodized salt were Senegal (29·5 %) followed by Tanzania (21·3 %), Ethiopia (14·0 %), Malawi (11·6 %) and Angola (10·8 %). The rate of non-iodized salt was less than 1 % in Rwanda (0·3 %), Uganda (0·5 %) and Burundi (0·8 %). Stepwise multivariable logistic regression showed that women were more likely to be using non-iodized salt (adjusted OR; 95 % CI) if they were poor (1·62; 1·48, 1·78), pregnant (1·16; 1·04, 1·29), aged 15-24 years (v. older: 1·14; 1·04, 1·24) and were not literate (1·14; 1·06, 1·23).Conclusions: The use of non-iodized salt varies among SSA countries. The higher level of use of non-iodized salt among poor, young women and pregnant women is particularly concerning. [ABSTRACT FROM AUTHOR]

Background: Malaria and HIV are common infections in Africa and cause substantial morbidity and mortality in pregnant women. We aimed to assess the association of malaria with anemia in pregnant women and to explore the joint effects of malaria and HIV infection on anemia in pregnant women.Methods: We used nationally representative, cross-sectional demographic and health surveys (DHS) that were conducted between 2012 and 2017 across 7 countries of sub-Saharan Africa (Burundi, the Democratic Republic of the Congo, Gambia, Ghana, Mali, Senegal and Togo). The outcome variables were anemia (defined as a hemoglobin concentration < 110 g/L), and hemoglobin concentration on a continuous scale, in pregnant women at the time of the interview. We used generalized linear mixed-effects models to account for the nested structure of the data. We adjusted models for individual covariates, with random effects of the primary sampling unit nested within a country.Results: A total of 947 pregnant women, ages, 15-49 y, were analyzed. Prevalence of malaria only, HIV only, and malaria- HIV coinfection in pregnant women was 31% (95% CI: 28.5 to 34.5%, n = 293), 1.3% (95% CI: 0.77 to 2.4%, n = 13) and 0.52% (95% CI: 0.02 to 1.3%, n = 5) respectively. Overall prevalence of anemia was 48.3% (95% CI: 45.1 to 51.5%). The anemia prevalence in pregnant women with malaria infection only was 56.0% (95% CI: 50.1 to 61.7%); HIV infection only, 62.5% (95% CI: 25.9 to 89.8%); malaria- HIV coinfection, 60.0 (95% CI: 17.0-92.7%) and without either infection, 44.6% (95% CI: 40.7 to 48.6%). In the fully adjusted models, malaria infection was associated with 27% higher prevalence of anemia (95% CI of prevalence ratio: 1.12 to 1.45; p = 0.004), and 3.4 g/L lower hemoglobin concentration (95% CI: - 5.01 to - 1.79; p = 0.03) compared to uninfected pregnant women. The prevalence of HIV infection and malaria-HIV coinfection was too low to allow meaningful analysis of their association with anemia or hemoglobin concentration.Conclusion: Malaria was associated with an increased prevalence of anemia during pregnancy. [ABSTRACT FROM AUTHOR]

Measurement-based care (MBC) is an evidence-based approach to improving outcomes of mental health services. There is considerable interest in implementing it in clinical practice settings. However, relatively little attention has been paid to the pragmatics of developing and implementing MBC in youth mental health. This paper describes one effort to accomplish this goal. After a brief discussion of the advantages of MBC, the process, and initial implementation of the Penn State Psychiatry Clinical Assessment and Rating Evaluation System for Youth (PCARES-Youth) is described. Results of a pilot project of PCARES-Youth are presented, including a survey of clinicians about their experiences with the initiative. Finally, lessons learned and next steps of the project are discussed. [ABSTRACT FROM AUTHOR]

Objective: Recruitment to randomized clinical trials is expensive and often falls short of goals, limiting achievement of measurable outcomes. To prepare for a trial in patients with incomplete forms of lupus, a mock recruitment protocol was carried out at 4 proposed study sites. The objective was to determine levels of interest in patients and to uncover potential barriers to enrollment.Methods: After obtaining institutional review board approval, study coordinators approached individuals who generally fit proposed criteria for the trial. A standardized script was followed in a structured interview. Levels of interest were determined and any reasons for concerns were collected with an open-ended format.Results: A total of 45 subjects were interviewed, of which 73% expressed an interest in the trial, and 64% said they were likely to enroll. Concerns of those who were not interested included risk of hydroxychloroquine, desire not to receive placebo, and lack of time for participation.Conclusion: The mock recruitment suggests that the trial will be attractive to suitable patients. The concerns raised support other data indicating that provision of information is crucial to achieving enrollment goals. Mock recruitment of potential investigators should be considered also to address referral concerns. [ABSTRACT FROM AUTHOR]

Background: Insomnia has been associated in cross‐sectional studies with increased beta (15–35 Hz) electroencephalogram (EEG) power during nonrapid eye movement (NREM) sleep, an index of cortical hyperarousal. However, it is unknown whether this cortical hyperarousal is present before individuals with insomnia develop the disorder. To fill this gap, we examined the association of childhood sleep high‐frequency EEG activity with incident insomnia symptoms (i.e., absence of insomnia symptoms in childhood but presence in adolescence). Methods: We studied a case–control subsample of 45 children (6–11 years) from the Penn State Child Cohort, a population‐based random sample of 421 children, who were followed up after 8 years as adolescents (13–20 years). We examined low‐beta (15–25 Hz) and high‐beta (25–35 Hz) relative power at central EEG derivations during NREM sleep and, in secondary analyses, during sleep onset latency, sleep onset, and REM sleep. Incident insomnia symptoms were defined as the absence of parent‐reported difficulty falling and/or staying asleep during childhood and a self‐report of these insomnia symptoms during adolescence. Results: Childhood high‐beta power during NREM sleep was significantly increased in children who developed insomnia symptoms in adolescence (n = 25) as compared to normal sleeping controls (n = 20; p = .03). Multivariable‐adjusted logistic regression models showed that increased childhood high‐beta EEG power during NREM sleep was associated with a threefold increased odds (95% CI = 1.12–7.98) of incident insomnia symptoms in adolescence. No other significant relationships were observed for other sleep/wake states or EEG frequency bands. Conclusions: Increased childhood high‐frequency EEG power during NREM sleep is associated with incident insomnia symptoms in adolescence. This study indicates that cortical hyperarousal during sleep may be a premorbid neurophysiological sign of insomnia, which may mediate the increased risk of psychiatric disorders associated with insomnia. [ABSTRACT FROM AUTHOR]

Background: Onset of systemic lupus erythematosus (SLE) is preceded by a preclinical phase characterized by expression of autoantibodies and nonspecific clinical symptoms. Hydroxychloroquine is a treatment for lupus that is widely used based on longstanding experience and a very good safety profile. Existing data suggest that treatment with hydroxychloroquine may postpone the onset of disease. However, prospective studies that prove and quantify the efficacy of hydroxychloroquine in the preclinical phase of lupus have not been done. This study will test the hypothesis that early hydroxychloroquine use can prevent accumulation of clinical abnormalities and modify immune responses that define SLE.Methods: A randomized, double-blind, placebo-controlled trial of hydroxychloroquine vs placebo will be conducted. Participants will have incomplete lupus erythematosus as defined by the presence of antinuclear antibody (ANA) positivity at a titer of 1:80 or greater, as well as one or two additional criteria from the 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria. The age range will be 15-45 years and the treatment phase will be 96 weeks. The primary endpoint will be the increase in the number of features of SLE defined by the 2012 SLICC classification schema. Secondary outcomes will include the proportion of participants who transition to a classification of SLE as defined by SLICC criteria.Discussion: A major challenge for improving therapies in patients with SLE is early detection of disease. The ANA test that is widely used to screen for SLE has low specificity and interpretation of its significance is challenging. The Study of Anti-Malarials in Incomplete Lupus Erythematosus (SMILE) trial will provide insights into the appropriate target population for intervention, and will assess whether hydroxychloroquine can slow progression as measured by the accumulation of criteria. Ophthalmologic safety in this population will be assessed. The study will investigate candidate biomarkers that will guide treatment decisions and will accumulate a specimen biobank that will be available to the lupus research community for further in-depth mechanistic studies. This trial is a first step toward testing the feasibility of disease prevention strategies in SLE.Trial Registration: ClinicalTrials.gov, NCT 03030118 . Registered on 24 January 2017. [ABSTRACT FROM AUTHOR]

Numerous studies document increased health risks from exposure to traffic and traffic-related particulate matter (PM). However, many studies use simple exposure metrics to represent traffic-related PM, and/or are limited to small geographic areas over relatively short (e.g., 1 year) time periods. We developed a modeling approach for the conterminous US from 1999 to 2011 that applies a line-source Gaussian plume dispersion model using several spatially and/or temporally varying inputs (including daily meteorology) to produce high spatial resolution estimates of primary near-road traffic-related PM levels. We compared two methods of spatially averaging traffic counts: spatial smoothing generalized additive models and kernel density. Also, we evaluated and validated the output from the line-source dispersion modeling approach in a spatio-temporal model of 24-h average PM < 2.5 μm (PM2.5) elemental carbon (EC) levels. We found that spatial smoothing of traffic count point data performed better than a kernel density approach. Predictive accuracy of the spatio-temporal model of PM2.5 EC levels was moderate for 24-h averages (cross-validation (CV) R2 = 0.532) and higher for longer averaging times (CV R2 = 0.707 and 0.795 for monthly and annual averages, respectively). PM2.5 EC levels increased monotonically with line-source dispersion model output. Predictive accuracy was higher when the spatio-temporal model of PM2.5 EC included line-source dispersion model output compared to distance to road terms. Our approach provides estimates of primary traffic-related PM levels with high spatial resolution across the conterminous US from 1999 to 2011. Spatio-temporal model predictions describe 24-h average PM2.5 EC levels at unmeasured locations well, especially over longer averaging times. [ABSTRACT FROM AUTHOR]

Based on previous studies reporting on the association of objective sleep duration and physiologic changes (i.e., increased cortisol) in children, we examined the role of objective sleep duration on differentiating behavioral profiles in children with insomnia symptoms. Seven hundred children (ages 5-12, 47.8% male) from the Penn State Child Cohort underwent a nine-hour polysomnography and parent completed Pediatric Behavior Scale. Insomnia symptoms were defined as parent report of difficulty falling and/or staying asleep, sleep disordered breathing as an AHI of ≥1, and objective short sleep duration as a total sleep time < 7.7 h. Children with insomnia symptoms demonstrated more overall behavioral problems than controls. Significant interactions between insomnia symptoms and objective sleep duration on scores of externalizing behaviors, mood variability and school problems were found. Profile analyses showed that children with insomnia symptoms and normal sleep duration were associated with clinically elevated externalizing behaviors, inattention, mood variability, and school problems, while children with insomnia and short sleep duration were associated with an overall elevated profile in which internalizing behaviors were more prominent. Childhood insomnia symptoms are associated with a wide array of behavioral problems, for which objective sleep duration is useful in differentiating behavioral profiles. Children with insomnia symptoms and normal sleep duration had a behavioral profile consistent with limit-setting and rule-breaking behaviors, while children with insomnia symptoms and short sleep duration had a behavioral profile more consistent with internalizing behaviors resembling that of psychophysiological disorders. [ABSTRACT FROM AUTHOR]

Objective. The study goals were to evaluate performance of SLE classification criteria, to define patients with incomplete lupus erythematosus (ILE), and to probe for features in these patients that might be useful as indicators of disease status and hydroxychloroquine response. Methods. Patients with ILE (N=70) and SLE (N=32) defined by the 1997 American College of Rheumatology criteria were reclassified using the 2012 Systemic Lupus International Collaborating Clinics criteria. Disease activity, patient reported outcomes, and levels of Type I interferon- (IFN-) inducible genes, autoantibodies, and cytokines were measured. Subgroups treated with hydroxychloroquine (HCQ) were compared to patients not on this drug. Results. The classification sets were correlated (R2=0.87). ILE patients were older (P=0.0043) with lower disease activity scores (P<0.001) and greater dissatisfaction with health status (P=0.034) than SLE patients. ILE was associated with lower levels of macrophage-derived cytokines and levels of expressed Type I IFN-inducible genes. Treatment of ILE with HCQ was associated with better self-reported health status scores and lower expression levels of Type I IFN-inducible genes than ILE patients not on HCQ. Conclusion. The 2012 SLICC SLE classification criteria will be useful to define ILE in trials. Patients with ILE have better health status and immune profiles when treated with HCQ. [ABSTRACT FROM AUTHOR]

Three competing genetic models-additive, dominant, and recessive-are often considered in genetic association analysis. We propose and develop a calibrated Bayes approach for comparing these competing models that has the desired property of giving equal support to the three models when no genetic association is present. The naïve approach with noncalibrated priors is shown to producemisleading Bayes factors. Themethod is fully developedwith simulation studies, real data analyses, and an efficient algorithm based on an asymptotic approximation. An illuminating connection to the Kullback-Leibler divergence is also established. The proposed calibrated prior can serve as a reference prior for a genetic association study or as a common baseline prior for comparing Bayes analyses of different datasets. [ABSTRACT FROM AUTHOR]

Longitudinal studies that have examined the association of insomnia with incident depression using objective sleep measures are very limited. The aim of this study was to examine the predictive role of the severity of insomnia for incident depression in a general population sample using psychometric and polysomnographic data. From a random, general population sample of 1741 individuals of the Penn State Adult Cohort, 1137 adults without depression were followed up with a structured telephone interview after 7.5 years. All subjects completed a full medical evaluation, 1-night polysomnogram and Multiphasic Minnesota Personality Inventory at baseline. The incidence of depression was 15%. Poor sleep (odds ratio = 1.5, P = 0.001) and insomnia (odds ratio = 1.9, P = 0.031) were significantly associated with incident depression. The odds of incident depression were highest (odds ratio = 2.2, P = 0.019) in insomnia with objective short sleep duration and independent of Multiphasic Minnesota Personality Inventory Ego Strength scores, an index of poor coping resources. The persistence of insomnia and worsening of poor sleep into insomnia significantly increased the odds of incident depression (odds ratios ranged from 1.8 to 6.3), whereas their full remission did not (odds ratio ranged from 1.2 to 1.8). Insomnia with short sleep duration is associated with incident depression independent of poor coping resources, whereas the association of insomnia with normal sleep duration with incident depression was mediated by poor coping resources. Persistence and worsening of poor sleep or insomnia, but not their full remission, are significant predictors of incident depression. These data suggest that there is a significant relationship between the severity of insomnia and incident depression. [ABSTRACT FROM AUTHOR]

Purpose: To assess the impact of obesity and population attributes on the circadian pattern of cardiac autonomic modulation (CAM) in a population-based sample of adolescents. Methods: We used data from 421 adolescents who completed the follow-up exam in the Penn State Children Cohort study. CAM was assessed by heart rate variability (HRV) analysis of beat-to-beat, normal R-R intervals from a 24-hour ECG, on a 30-minute basis. The HRV indices included frequency-domain (HF, LF, and LF/HF ratio) and time-domain (SDNN, RMSSD, and HR) variables. Nonlinear mixed-effect models were used to calculate a cosine periodic curve, each having three parameters quantifying its circadian period: M (mean levels of the HRV variables), Â (amplitude of the oscillation), and θ (the time of the highest oscillation). Results: The mean (SD) age was 16.9 (2.2) years, with 54 % male and 77 % white. The mean BMI percentile was 66, with 16 % obese (BMI percentile ≥ 95). Overall, HF (a marker of parasympathetic modulation) gradually increased from the late afternoon, reached peak amplitude around 3 a.m., and then decreased throughout the daytime until late afternoon. In contrast, obesity had adverse effects on all circadian parameters. The age, sex and race showed varying differences on the CAM circadian parameters. The adjusted means (95 %Cls) of M, Â, and θ for HF were 5.99 (5.79-6.19), 0.77 (0.66-0.89), 3:15 (2:15-4:15) a.m., and 6.21 (6.13-6.29), 0.66 (0.61-0.70), 2:45 (2:30-3:15) a.m. for obese and non-obese subjects, respectively. Conclusion: The circadian pattern of CAM can be quantified by the three cosine parameters. Obesity is associated with lower HRV even in young individuals like children/adolescents. [ABSTRACT FROM AUTHOR]

The epidemic of childhood obesity is becoming a major predictor for risk of cardiovascular diseases (CVD) and mortality during adulthood. Alterations in the morphology of the heart due to obesity could be a predictor for the dysfunction of cardiac autonomic modulation (CAM). A number of epidemiologic studies have evaluated the effect of obesity and CAM in children, finding that obesity impaired the balance of CAM toward a sympathetic overflow and reduced parasympathetic modulation, a significant predictor of CVD morbidity and mortality in adults. Lifestyle modifications, for example long-term exercise programs, have been shown to improve CAM in the obese. This review discusses the recent evidence on childhood and adolescent obesity and its impact on CAM, as well as how early lifestyle changes could help improve CAM, which may in turn reduce the burden of CVD in adults. [ABSTRACT FROM AUTHOR]

Background Insomnia symptoms are the most common parent-reported sleep complaints in children; however, little is known about the pathophysiology of childhood insomnia symptoms, including their association with hypothalamic-pituitary-adrenal (HPA) axis activation. The objective of this study is to examine the association between parent-reported insomnia symptoms, objective short sleep duration and cortisol levels in a population-based sample of school-aged children. Design A sample of 327 children from the Penn State Child Cohort (5-12 years old) underwent 9-h overnight polysomnography and provided evening and morning saliva samples to assay for cortisol. Objective short sleep duration was defined based on the median total sleep time (i.e., < 7·7 h). Parent-reported insomnia symptoms of difficulty initiating and/or maintaining sleep were ascertained with the Pediatric Behavior Scale. Results Children with parent-reported insomnia symptoms and objective short sleep duration showed significantly increased evening (0·33 ± 0·03 μg/dL) and morning (1·38 ± 0·08 μg/dL) cortisol levels. In contrast, children with parent-reported insomnia symptoms and 'normal' sleep duration showed similar evening and morning cortisol levels (0·23 ± 0·03 μg/dL and 1·13 ± 0·08 μg/dL) compared with controls with 'normal' (0·28 ± 0·02 μg/dL and 1·10 ± 0·04 μg/dL) or short (0·28 ± 0·02 μg/dL and 1·13 ± 0·04 μg/dL) sleep duration. Conclusions Our findings suggest that insomnia symptoms with short sleep duration in children may be related to 24-h basal or responsive physiological hyperarousal. Future studies should explore the association of insomnia symptoms with short sleep duration with physical and mental health morbidity. [ABSTRACT FROM AUTHOR]

BACKGROUND: The mechanisms underlying the relationship between particulate matter (PM) air pollution and cardiac disease are not fully understood. OBJECTIVES: We examined the effects and time course of exposure to fine PM [aerodynamic diameter ≤ 2.5 µm (PM2.5)] on cardiac arrhythmia in 105 middle-age community-dwelling healthy nonsmokers in central Pennsylvania. METHODS: The 24-hr beat-to-beat electrocardiography data were obtained using a high-resolution Holter system. After visually identifying and removing artifacts, we summarized the total number of premature ventricular contractions (PVCs) and premature atrial contractions (PACs) for each 30-min segment. A personal PM2.5 nephelometer was used to measure individual-level real-time PM2.5 exposures for 24 hr. We averaged these data to obtain 30-min average time-specific PM2.5 exposures. Distributed lag models under the framework of negative binomial regression and generalized estimating equations were used to estimate the rate ratio between 10-µg/m3 increases in average PM2.5 over 30-min intervals and ectopy counts. RESULTS: The mean ± SD age of participants was 56 ± 8 years, with 40% male and 73% non-Hispanic white. The 30-min mean ± SD for PM2.5 exposure was 13 ± 22 µg/m3, and PAC and PVC counts were 0.92 ± 4.94 and 1.22 ± 7.18. Increases of 10 µg/m3 in average PM2.5 concentrations during the same 30 min or the previous 30 min were associated with 8% and 3% increases in average PVC counts, respectively. PM2.5 was not significantly associated with PAC count. CONCLUSION: PM2.5 exposure within approximately 60 min was associated with increased PVC counts in healthy individuals. [ABSTRACT FROM AUTHOR]

Objectives: To examine the circadian pattern of cardiac autonomic modulation (CAM) and its attributes in general population. Methods: We obtained 24-h beat-to-beat RR data using a high resolution 12-lead Holter ECG in a community-dwelling sample of 115 non-smokers. We performed heart rate variability (HRV) analysis on the normal RRs from each 5-min segment to obtain time-specific HRV indices: high (HF; 0.15-0.40 Hz) and low (LF; 0.04-0.15 Hz) frequency powers, standard deviation of RR intervals (SDNN), and the square root of the mean of the sum of the squared differences of the adjacent RR intervals (RMSSD). For each individual, we fit the segment-specific HRV data to a cosine periodic function, and estimated 3 individual-level cosine function parameters to quantify the circadian variation: the mean ( M), amplitude ( A), and acrophase ( θ). We then used a random-effects meta-analysis to summarize the M, A, and θ, and their 95% confidence intervals (CI). Results: The mean age was 56 (SD 8) years, with 63% female and 76% white. The averages of M, A and θ (95%CI) of log HF were 3.59 (3.43-3.76) ms, 0.61 (0.54-0.68) ms, and 3:10 (2:25-3:55) AM, respectively, and that of RMSSD were 22.3 (20.5-24.1) ms, 6.5 (5.4-7.5) ms, 3:45 (2:55-4:35) AM, respectively. Older age is associated with lower mean of HRV. Males have higher oscillation amplitude than females. The acrophase of LF/HF was earlier in females than in males, and in younger individuals than in older individuals. Conclusions: The circadian pattern of CAM can be quantified by 3 cosine parameters of HRV, which are correlated with age and gender. [ABSTRACT FROM AUTHOR]

The acute effects and the time course of fine particulate pollution (PM2.5) on atrial fibrillation/flutter (AF) predictors, including P-wave duration, PR interval duration, and P-wave complexity, were investigated in a community-dwelling sample of 106 nonsmokers. Individual-level 24-h beat-to-beat electrocardiogram (ECG) data were visually examined. After identifying and removing artifacts and arrhythmic beats, the 30-min averages of the AF predictors were calculated. A personal PM2.5 monitor was used to measure individual-level, real-time PM2.5 exposures during the same 24-h period, and corresponding 30-min average PM2.5 concentration were calculated. Under a linear mixed-effects modeling framework, distributed lag models were used to estimate regression coefficients (βs) associating PM2.5 with AF predictors. Most of the adverse effects on AF predictors occurred within 1.5-2 h after PM2.5 exposure. The multivariable adjusted βs per 10-μg/m3 rise in PM 2.5 at lag 1 and lag 2 were significantly associated with P-wave complexity. PM2.5 exposure was also significantly associated with prolonged PR duration at lag 3 and lag 4. Higher PM2.5 was found to be associated with increases in P-wave complexity and PR duration. Maximal effects were observed within 2 h. These findings suggest that PM2.5 adversely affects AF predictors; thus, PM2.5 may be indicative of greater susceptibility to AF. [ABSTRACT FROM AUTHOR]

Objective. To examine the cross-sectional association between measurements of obesity and subclinical impairment of cardiac autonomic modulation (CAM) in a population-based sample of children. Methods. Data from 616 grade K-5 children randomly selected from Central Pennsylvania were utilized. Obesity was defined using the International Obesity Task Force (IOTF) age- and sex-specific cut-off criteria and classified as normal weight, overweight, and obese. CAM was measured by heart rate variability (HRV) analysis of beat-to-beat RR intervals, including time domain measures i.e., the standard deviation of all RR intervals (SDNN), the square root of the mean of the sum of squares of differences between adjacent RR intervals (RMSSD), and mean heart rate (HR); and frequency domain measures i.e., high frequency power (HF), low frequency power (LF), and LF/HF ratio. Results. The prevalence of obesity and overweight in children was 12.3%, and 16.5%, respectively. Age, race, sex, and sleep disorder breathing (SDB) adjusted means (standard error, SE) of SDNN were 98 (1.24), 90.2 (2.58), and 81.9 (3.03) milliseconds (ms) in normal weight, overweight, and obese groups, respectively; and that for (log) HF were 6.83 (0.04), 6.56 (0.08), and 6.35 (0.09) ms2, respectively. Comparing the magnitude of effects from body mass index (BMI), weight, and height percentiles, and waist circumference on HRV indices revealed that body weight was the strongest correlate of HRV indices. Conclusion. Childhood obesity is significantly associated with lower HRV, indicative of sympathetic overflow unopposed by parasympathetic modulation. These findings support the need to target childhood-obesity before traditional ''high risk age'' for cardiac events. [ABSTRACT FROM AUTHOR]

Genomic imprinting is a phenomenon in which the same allele is expressed differently, depending on its parental origin. Such a phenomenon, also called the parent-of-origin effect, has been recognized to play a pivotal role in embryological development and pathogenesis in many species. Here we propose a statistical design for detecting imprinted loci that control quantitative traits based on a random set of three-generation families from a natural population in humans. This design provides a pathway for characterizing the effects of imprinted genes on a complex trait or disease at different generations and testing transgenerational changes of imprinted effects. The design is integrated with population and cytogenetic principles of gene segregation and transmission from a previous generation to next. The implementation of the EM algorithm within the design framework leads to the estimation of genetic parameters that define imprinted effects. A simulation study is used to investigate the statistical properties of the model and validate its utilization. This new design, coupled with increasingly used genome-wide association studies, should have an immediate implication for studying the genetic architecture of complex traits in humans. [ABSTRACT FROM AUTHOR]

In 106 community-dwelling middle-aged non-smokers we examined the time-course and the acute effects of fine particles (PM2.5) on heart rate variability (HRV), which measures cardiac autonomic modulation (CAM). Twenty-four hours beat-to-beat ECG data were visually examined. Artifacts and arrhythmic beats were removed. Normal beat-to-beat RR data were used to calculate HRV indices. Personal PM2.5 nephelometry was used to estimate 24-h individual-level real-time PM2.5 exposures. We use linear mixed-effects models to assess autocorrelation- and other major confounder-adjusted regression coefficients between 1-6 h moving averages of PM2.5 and HRV indices. The increases in preceding 1-6 h moving averages of PM2.5 was significantly associated with lower HF, LF, and SDNN, with the largest effect size at 4-6 h moving averages and smallest effects size at 1 h moving average. For example, a 10 μg/m3 increase in 1 and 6-h moving averages was associated with 0.027 and 0.068 ms2 decrease in log-HF, respectively, and with 0.024 and 0.071 ms2 decrease in log-LF, respectively, and with 0.81 and 1.75 ms decrease in SDNN, respectively (all P-values <0.05). PM2.5 exposures are associated with immediate impairment of CAM. With a time-course of within 6 h after elevated PM2.5 exposure, with the largest effects around 4-6 h. [ABSTRACT FROM AUTHOR]

Background: The mechanisms for the relationship between particulate pollution and cardiac disease are not fully understood. Objective: We examined the effects and time course of exposure to fine particulate matter ⩽ 2.5 μm in aerodynamic diameter (PM2.5) on ventricular repolarization of 106 nonsmoking adults who were living in communities in central Pennsylvania. Methods: The 24-hr beat-to-beat electrocardiogram (ECG) data were obtained using a highresolution 12-lead Holter system. After visually identifying and removing artifacts and arrhythmic beats, we summarized normal beat-to-beat QTs from each 30-min segment as heart rate (HR)- corrected QT measures: QT prolongation index (QTI), Bazett's HR-corrected QT (QTcB), and Fridericia's HR-corrected QT (QTcF). A personal PM2.5 monitor was used to measure individuallevel real-time PM2.5 exposures for 24 hr. We averaged these data and used 30-min time-specific average PM2.5 exposures. Results: The mean age of the participants was 56 ± 8 years, with 41% male and 74% white. The means ± SDs for QTI, QTcB, and QTcF were 111 ± 6.6, 438 ± 23 msec, and 422 ± 22 msec, respectively; and for PM2.5, the mean ± SD was 14 ± 22 μg/m3. We used distributed lag models under a framework of linear mixed-effects models to assess the autocorrelation-corrected regression coefficients (β) between 30-min PM2.5 and the HR-corrected QT measures. Most of the adverse ventricular repolarization effects from PM2.5 exposure occurred within 3-4 hr. The multivariable adjusted β (SE, p-value) due to a 10-μg/m3 increase in lag 7 PM2.5 on QTI, QTcB, and QTcF were 0.08 (0.04, p < 0.05), 0.22 (0.08, p < 0.01), and 0.09 (0.05, p < 0.05), respectively. Conclusions: Our results suggest a significant adverse effect of PM2.5 on ventricular repolarization. The time course of the effect is within 3-4 hr of elevated PM2.5. [ABSTRACT FROM AUTHOR]

Objective: We examined the joint effects of insomnia and objective short sleep duration, the combination of which is associated with higher morbidity, on diabetes risk.Research Design and Methods: A total of 1,741 men and women randomly selected from Central Pennsylvania were studied in the sleep laboratory. Insomnia was defined by a complaint of insomnia with duration of >or=1 year, whereas poor sleep was defined as a complaint of difficulty falling asleep, staying asleep, or early final awakening. Polysomnographic sleep duration was classified into three categories: >or=6 h of sleep (top 50% of the sample); 5-6 h (approximately third quartile of the sample); and 126 mg/dl or use of medication. In the logistic regression model, we simultaneously adjusted for age, race, sex, BMI, smoking, alcohol use, depression, sleep-disordered breathing, and periodic limb movement.Results: Chronic insomnia but not poor sleep was associated with a higher risk for diabetes. Compared with the normal sleeping and >or=6 h sleep duration group, the highest risk of diabetes was in individuals with insomnia and Conclusions: Insomnia with short sleep duration is associated with increased odds of diabetes. Objective sleep duration may predict cardiometabolic morbidity of chronic insomnia, the medical impact of which has been underestimated. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- We examined the joint effects of insomnia and objective short sleep duration, the combination of which is associated with higher morbidity, on diabetes risk. RESEARCH DESIGN AND METHODS -- A total of 1,741 men and women randomly selected from Central Pennsylvania were studied in the sleep laboratory. Insomnia was defined by a complaint of insomnia with duration of ≥1 year, whereas poor sleep was defined as a complaint of difficulty falling asleep, staying asleep, or early final awakening. Polysomnographic sleep duration was classified into three categories: ≥6 h of sleep (top 50% of the sample); 5-6 h (approximately third quartile of the sample); and ≤5 h (approximately the bottom quartile of the sample). Diabetes was defined either based on a fasting blood glucose >126 mg/dl or use of medication. In the logistic regression model, we simultaneously adjusted for age, race, sex, BMI, smoking, alcohol use, depression, sleep-disordered breathing, and periodic limb movement. RESULTS-- Chronic insomnia but not poor sleep was associated with a higher risk for diabetes. Compared with the normal sleeping and ≥6 h sleep duration group, the highest risk of diabetes was in individuals with insomnia and ≤5 h sleep duration group (odds ratio [95% CI] 2.95 [1.2-7.0]) and in insomniacs who slept 5-6 h (2.07 [0.68-6.4]). CONCLUSIONS-- Insomnia with short sleep duration is associated with increased odds of diabetes. Objective sleep duration may predict cardiometabolic morbidity of chronic insomnia, the medical impact of which has been underestimated. [ABSTRACT FROM AUTHOR]

The interaction between ambient air pollution and asthma medication remains unclear. The authors compared airway inflammation response to air pollution among asthmatics. Increases of 10 ppb of nitrogen dioxide (NO2) and of 10 μg/m3 of particulate matter < 10 micron in diameter (PM10) daily concentrations were associated with an increase in exhaled nitric oxide (eNO) of 0.13 ppb (95% confidence interval = 0.06, 0.19) and of 0.07 ppb (95% confidence interval = 0.02, 0.12), respectively, in models adjusted for important covariates. The results show that the medication could not counteract airway inflammation effects of air pollution. Specifically, the patients on triamcinolone decreased the sensitivity to PM10 but increased the sensitivity to NO2. The patients on salmeterol were more vulnerable to both NO2 and PM10. This study indicates that the current pollution levels may still enhance airway inflammation among patients with persistent asthma even when they are on asthma medications. [ABSTRACT FROM AUTHOR]

BACKGROUND: Ambient particulate matter (PM) air pollution is associated with coronary heart disease, but the pathways underlying the association remain to be elucidated. METHODS: We studied the association between PM and ischemia among 57,908 Women's Health Initiative clinical trial participants from 1999--2003. We used the Minnesota Code criteria to identify ST-segment and T-wave abnormalities, and estimated T amplitude (microvolt) from resting, standard 12-lead electrocardiogram (ECG). We used U.S. Environmental Protection Agency's monitor data to estimate concentrations of PM < 2.5 µm (PM2.5) at geocoded participant addresses over 6 days before the ECGs (lag0 through lag5). We excluded 2,379 women with ECG QRS duration ≥ 120 msec. RESULTS: Overall, 6% of the remaining 55,529 women (52--90 years of age; 83% non-Hispanic white) had ST abnormalities and 16% had T abnormalities. Lead-specific T amplitude was normally distributed (range of means from --14 to 349 µV). PM2.5 (mean ± SD) averaged over lag0--2 was 14 ± 7 µg/m3. In logistic and linear regression models adjusted for demographic, clinical, temporal, and climatic factors, a 10-µg/m3 increase in lag0--2 PM2.5 was associated with a 4% [95% confidence interval (CI), --3%, to 10%] increase in the odds of ST abnormality and a 5% (95% CI, 0% to 9%) increase in the odds of T abnormality. We observed corresponding decreases in T amplitude in all exam sites and leads except lead V1, reaching a minimum of --2 µV (95% CI, --5 to 0 µV) in lead V3. CONCLUSIONS: Short-term PM2.5 exposure is associated with ECG evidence of myocardial ischemia among postmenopausal women. The principal manifestations include subclinical but potentially arrhythmogenic ST--T abnormalities and decreases in T amplitude. [ABSTRACT FROM AUTHOR]

Various studies have reported an inverse association between serum albumin level and incident coronary heart disease (CHD), though biologic mechanisms have not been established. The authors examined the association between serum albumin level and CHD in the Atherosclerosis Risk in Communities cohort, comprising 14,506 White and African-American middle-aged men and women. The mean albumin level in this population was 3.9 g/dl (standard deviation 0.3). During 5.2 years of follow-up, 470 incident CHD events occurred. The hazard ratio for incident CHD associated with a 1-standard deviation decrease in serum albumin level was 1.26 (95% confidence interval (CI): 1.15, 1.38) after adjustment for age, gender, and ethnicity and 1.18 (95% CI: 1.07, 1.30) after additional adjustment for covariates related to CHD. Hazard ratios were similar across gender and ethnic groups. However, there was statistically significant effect modification by smoking status, with hazard ratios of 1.01 (95% CI: 0.84, 1.22) among never smokers, 1.09 (95% CI: 0.92, 1.30) among former smokers, and 1.35 (95% CI: 1.17, 1.54) among current smokers. Further adjustment for factors related to renal disease, nutrition, platelet aggregation, inflammation, use of angiotensin-converting enzyme inhibitors, and hemostasis factors attenuated the albumin-CHD relation only slightly. In this study, serum albumin was inversely associated with incident CHD at the baseline examination in current smokers but not in never or former smokers. Albumin level may be a marker of susceptibility to the inflammatory response that results from smoking. Am J Epidemiol 2000;151:468–77. [ABSTRACT FROM PUBLISHER]

Background: Published studies of geocoding accuracy often focus on a single geographic area, address source or vendor, do not adjust accuracy measures for address characteristics, and do not examine effects of inaccuracy on exposure measures. We addressed these issues in a Women's Health Initiative ancillary study, the Environmental Epidemiology of Arrhythmogenesis in WHI. Results: Addresses in 49 U.S. states (n = 3,615) with established coordinates were geocoded by four vendors (A-D). There were important differences among vendors in address match rate (98%; 82%; 81%; 30%), concordance between established and vendor-assigned census tracts (85%; 88%; 87%; 98%) and distance between established and vendor-assigned coordinates (mean ρ [meters]: 1809; 748; 704; 228). Mean ρ was lowest among street-matched, complete, zip-coded, unedited and urban addresses, and addresses with North American Datum of 1983 or World Geodetic System of 1984 coordinates. In mixed models restricted to vendors with minimally acceptable match rates (A-C) and adjusted for address characteristics, within-address correlation, and amongvendor heteroscedasticity of ρ, differences in mean ρ were small for street-type matches (280; 268; 275), i.e. likely to bias results relying on them about equally for most applications. In contrast, differences between centroid-type matches were substantial in some vendor contrasts, but not others (5497; 4303; 4210) pinteraction < 10-4, i.e. more likely to bias results differently in many applications. The adjusted odds of an address match was higher for vendor A versus C (odds ratio = 66, 95% confidence interval: 47, 93), but not B versus C (OR = 1.1, 95% CI: 0.9, 1.3). That of census tract concordance was no higher for vendor A versus C (OR = 1.0, 95% CI: 0.9, 1.2) or B versus C (OR = 1.1, 95% CI: 0.9, 1.3). Misclassification of a related exposure measure - distance to the nearest highway - increased with mean ? and in the absence of confounding, non-differential misclassification of this distance biased its hypothetical association with coronary heart disease mortality toward the null. Conclusion: Geocoding error depends on measures used to evaluate it, address characteristics and vendor. Vendor selection presents a trade-off between potential for missing data and error in estimating spatially defined attributes. Informed selection is needed to control the trade-off and adjust analyses for its effects. [ABSTRACT FROM AUTHOR]