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Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10(-4)). The strongest combined association was at rs1823125 (P=1.5 × 10(-10), minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10-8) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.© 2014 Nature America, Inc. All rights reserved.

Background: The major marker utilized to monitor COPD patients is forced expiratory volume in one second (FEV1). However, asingle measurement of FEV1 cannot reliably predict subsequent decline. Recent studies indicate that T lymphocytes and eosinophils are important determinants of disease stability in COPD. We therefore measured cytokine levels in the lung lavage fluid and plasma of COPD patients in order to determine if the levels of T cell or eosinophil related cytokines were predictive of the future course of the disease.Methods: Baseline lung lavage and plasma samples were collected from COPD subjects with moderately severe airway obstruction and emphysematous changes on chest CT. The study participants were former smokers who had not had a disease exacerbation within the past six months or used steroids within the past two months. Those subjects who demonstrated stable disease over the following six months (ΔFEV1 % predicted = 4.7 ± 7.2; N = 34) were retrospectively compared with study participants who experienced a rapid decline in lung function (ΔFEV1 % predicted = -16.0 ± 6.0; N = 16) during the same time period and with normal controls (N = 11). Plasma and lung lavage cytokines were measured from clinical samples using the Luminex multiplex kit which enabled the simultaneous measurement of several T cell and eosinophil related cytokines.Results and Discussion: Stable COPD participants had significantly higher plasma IL-2 levels compared to participants with rapidly progressive COPD (p = 0.04). In contrast, plasma eotaxin-1 levels were significantly lower in stable COPD subjects compared to normal controls (p < 0.03). In addition, lung lavage eotaxin-1 levels were significantly higher in rapidly progressive COPD participants compared to both normal controls (p < 0.02) and stable COPD participants (p < 0.05).Conclusion: These findings indicate that IL-2 and eotaxin-1 levels may be important markers of disease stability in advanced emphysema patients. Prospective studies will need to confirm whether measuring IL-2 or eotaxin-1 can identify patients at risk for rapid disease progression. © 2009 D'Armiento et al; licensee BioMed Central Ltd.

Background: Vitamin D is associated with lung function in cross-sectional studies, and vitamin D inadequacy is hypothesized to play a role in the pathogenesis of chronic obstructive pulmonary disease. Further data are needed to clarify the relation between vitamin D status, genetic variation in vitamin D metabolic genes, and cross-sectional and longitudinal changes in lung function in healthy adults. Methods: We estimated the association between serum 25-hydroxyvitamin D [25(OH)D] and cross-sectional forced expiratory volume in the first second (FEV1) in Framingham Heart Study (FHS) Offspring and Third Generation participants and the association between serum 25(OH)D and longitudinal change in FEV1 in Third Generation participants using linear mixed-effects models. Using a gene-based approach, we investigated the association between 241 SNPs in 6 select vitamin D metabolic genes in relation to longitudinal change in FEV1 in Offspring participants and pursued replication of these findings in a meta-analyzed set of 4 independent cohorts. Results: We found a positive cross-sectional association between 25(OH)D and FEV1 in FHS Offspring and Third Generation participants (P = 0.004). There was little or no association between 25(OH)D and longitudinal change in FEV1 in Third Generation participants (P = 0.97). In Offspring participants, the CYP2R1 gene, hypothesized to influence usual serum 25(OH)D status, was associated with longitudinal change in FEV1 (gene-based P < 0.05). The most significantly associated SNP from CYP2R1 had a consistent direction of association with FEV1 in the meta-analyzed set of replication cohorts, but the association did not reach statistical significance thresholds (P = 0.09). Conclusions: Serum 25(OH)D status was associated with cross-sectional FEV1, but not longitudinal change in FEV1. The inconsistent associations may be driven by differences in the groups studied. CYP2R1 demonstrated a gene-based association with longitudinal change in FEV1 and is a promising candidate gene for further studies. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study evaluates the variation in practice patterns associated with contrast-induced acute kidney injury (CI-AKI) and identifies clinical practices that have been associated with a reduction in CI-AKI. Background CI-AKI is recognised as a complication of invasive cardiovascular procedures and is associated with cardiovascular events, prolonged hospitalisation, end-stage renal disease, and all-cause mortality. Reducing the risk of CI-AKI is a patient safety objective set by the National Quality Forum. METHODS: This study prospectively collected quantitative and qualitative data from 10 centres, which participate in the Northern New England Cardiovascular Disease Study Group PCI Registry. Quantitative data were collected from the PCI Registry. Qualitative data were obtained through clinical team meetings to map care processes related to CI-AKI and focus groups to understand attitudes towards CI-AKI prophylaxis. Fixed and random effects modelling were conducted to test the differences across centres. RESULTS: Significant variation in rates of CI-AKI were found across 10 medical centres. Both fixed effects and mixed effects logistic regression demonstrated significant variability across centres, even after adjustment for baseline covariates (p<0.001 for both modelling approaches). Patterns were found in reported processes and clinical leadership that were attributable to centres with lower rates of CI-AKI. These included reducing nil by mouth (NPO) time to 4 h prior to case, and standardising volume administration protocols in combination with administering three to four high doses of N-acetylcysteine (1200 mg) for each patient. CONCLUSIONS: These data suggest that clinical leadership and institution-focused efforts to standardise preventive practices can help reduce the incidence of CI-AKI. [ABSTRACT FROM AUTHOR]

Rationale: Sleep-disordered breathing (SDB), the recurrent episodic disruption of normal breathing during sleep, affects as much as 17% of U.S. adults, and may be more prevalent in poor urban environments. SDB and air pollution have been linked to increased cardiovascular diseases and mortality, but the association between pollution and SDB is poorly understood.Objectives: We used data from the Sleep Heart Health Study (SHHS), a U.S. multicenter cohort study assessing cardiovascular and other consequences of SDB, to examine whether particulate air matter less than 10 μm in aerodynamic diameter (PM(10)) was associated with SDB among persons 39 years of age and older.Methods: Using baseline data from SHHS urban sites, outcomes included the following: the respiratory disturbance index (RDI); percentage of sleep time at less than 90% O(2) saturation; and sleep efficiency, measured by overnight in-home polysomnography. We applied a fixed-effect model containing a city effect, controlling for potential predictors. In all models we included both the 365-day moving averages of PM(10) and temperature (long-term effects) and the differences between the daily measures of these two predictors and their 365-day average (short-term effects).Measurements and Main Results: In summer, increases in RDI or percentage of sleep time at less than 90% O(2) saturation, and decreases in sleep efficiency, were all associated with increases in short-term variation in PM(10). Over all seasons, we found that increased RDI was associated with an 11.5% (95% confidence interval: 1.96, 22.01) increase per interquartile range increase (25.5°F) in temperature.Conclusions: Reduction in air pollution exposure may decrease the severity of SDB and nocturnal hypoxemia and may improve cardiac risk. [ABSTRACT FROM AUTHOR]

Rationale: Although obstructive sleep apnea is associated with physiological perturbations that increase risk of hypertension and are proatherogenic, it is uncertain whether sleep apnea is associated with increased stroke risk in the general population.Objectives: To quantify the incidence of ischemic stroke with sleep apnea in a community-based sample of men and women across a wide range of sleep apnea.Methods: Baseline polysomnography was performed between 1995 and 1998 in a longitudinal cohort study. The primary exposure was the obstructive apnea-hypopnea index (OAHI) and outcome was incident ischemic stroke.Measurements and Main Results: A total of 5,422 participants without a history of stroke at the baseline examination and untreated for sleep apnea were followed for a median of 8.7 years. One hundred ninety-three ischemic strokes were observed. In covariate-adjusted Cox proportional hazard models, a significant positive association between ischemic stroke and OAHI was observed in men (P value for linear trend: P = 0.016). Men in the highest OAHI quartile (>19) had an adjusted hazard ratio of 2.86 (95% confidence interval, 1.1-7.4). In the mild to moderate range (OAHI, 5-25), each one-unit increase in OAHI in men was estimated to increase stroke risk by 6% (95% confidence interval, 2-10%). In women, stroke was not significantly associated with OAHI quartiles, but increased risk was observed at an OAHI greater than 25.Conclusions: The strong adjusted association between ischemic stroke and OAHI in community-dwelling men with mild to moderate sleep apnea suggests that this is an appropriate target for future stroke prevention trials. [ABSTRACT FROM AUTHOR]

Rationale: Cross-sectional epidemiologic studies show an association between sleep-disordered breathing and hypertension, but only one cohort study has examined sleep-disordered breathing as a risk factor for incident hypertension.Objectives: To examine whether sleep-disordered breathing increases the risk of incident hypertension among persons 40 years of age and older.Methods: In a prospective cohort study, we analyzed data from 2,470 participants who at baseline did not have hypertension, defined as blood pressure of at least 140/90 mm Hg or taking antihypertensive medication. The apnea-hypopnea index (AHI), the number of apneas plus hypopneas per hour of sleep, was measured by overnight in-home polysomnography. We estimated odds ratios for developing hypertension during 5 years of follow-up according to baseline AHI.Measurements and Main Results: The odds ratios for incident hypertension increased with increasing baseline AHI; however, this relationship was attenuated and not statistically significant after adjustment for baseline body-mass index. Although not statistically significant, the observed association between a baseline AHI greater than 30 and future hypertension (odds ratio, 1.51; 95% confidence interval, 0.93-2.47) does not exclude the possibility of a modest association.Conclusions: Among middle-aged and older persons without hypertension, much of the relationship between AHI and risk of incident hypertension was accounted for by obesity. After adjustment for body mass index, the AHI was not a significant predictor of future hypertension, although a modest influence of an AHI greater than 30 on hypertension could not be excluded. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this article is to discuss strengths and weaknesses of quasi-experimental designs used in health care quality improvement research. The target groups for this article are investigators in plan-do-study-act (PDSA) quality improvement initiatives who wish to improve the rigor of their methodology and publish their work and reviewers who evaluate the quality of research proposals or published work.Summary: A primary purpose of PDSA quality improvement research is to establish a functional relationship between process changes in systems of health care and variation in outcomes. The time series design is the fundamental paradigm for demonstrating such functional relationships. The rigor of a PDSA quality improvement study design is strengthened using replication schemes and research methodology to address extraneous factors that weaken validity of observational studies.Conclusion: The design of PDSA quality improvement research should follow from the purpose and context of the project. Improving the rigor of the quality improvement literature will build a stronger foundation and more convincing justification for the study and practice of quality improvement in health care. [ABSTRACT FROM AUTHOR]

To examine the effect of lowest core body temperature on adverse outcomes associated with coronary artery bypass graft (CABG) surgery, data were collected on 7134 isolated CABG procedures carried out in New England from 1997 to 2000. Excluded from the analysis were patients with pump times < 60 and > 120 min and those operated upon using continuous warm cardioplegia. Data for lowest core temperature were divided into quartiles for analysis ( < 31.4 degrees C, 31.5-33.1 degrees C, 33.2-34.3 degrees C, and 2 34.4 degrees C). Patients with lower core body temperature on cardiopulmonary bypass (CPB) had higher in-hospital mortality rates. Crude mortality rates were 2.9% in the < or = 31.4 degrees C group, 2.1% in the 31.5-33.1 degrees C group, 1.3% in the 33.2-34.3 degrees C group and 1.2% in the > or = 34.4 degrees C group. The trend toward higher mortality as core temperature decreased was statistically significant (P(trend) < 0.001). Adjustment for differences in patient and disease characteristics did not significantly change the results and the test of trend remained significant (p < 0.001). Rates of perioperative stroke were somewhat lower in the colder groups. Rates in the two colder groups were 0.9% compared with 1.6% and 1.4% in the warmer groups (P(trend) = 0.082). This remained a marginal but significant trend after adjustment for possible confounding factors (p = 0.044). Low core body temperatures on CPB are associated with higher rates of in-hospital mortality among isolated CABG patients. Rates of intra- or postoperative use of an intra-aortic balloon pump are also higher with lower core temperatures. We concluded that temperature management strategy during CABG surgery has an important effect on patient outcomes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although additional dietary calcium is recommended frequently to reduce the risk of lead poisoning, its role in preventing lead absorption has not been evaluated clinically. OBJECTIVE: The objective was to determine the safety and to estimate the size of the effect of calcium- and phosphorus-supplemented infant formula in preventing lead absorption. DESIGN: One hundred three infants aged 3.5-6 mo were randomly assigned to receive iron-fortified infant formula (465 mg Ca and 317 mg P/L) or the same formula with added calcium glycerophosphate (1800 mg Ca and 1390 mg P/L) for 9 mo. RESULTS: There was no significant difference between groups in the mean ratio of urinary calcium to creatinine, serum calcium and phosphorus, or change in iron status (serum ferritin, total iron binding capacity). At month 4, the median (+/-SD) increase from baseline in blood lead concentration for the supplemented group was 57% of the increase for the control group (0.04 +/- 0.09 compared with 0.07 +/- 0.10 micromol/L; P = 0.039). This effect was attenuated during the latter half of the trial, with an overall median increase in blood lead concentration from baseline to month 9 of 0.12 +/- 0.13 micromol/L for the control group and 0.10 +/- 0.18 micromol/L for the supplemented group (P = 0.284). CONCLUSIONS: Supplementation did not have a measurable effect on urinary calcium excretion, calcium homeostasis, or iron status. The significant effect on blood lead concentrations during the first 4 mo was in the direction expected; however, because this was not sustained throughout the 9-mo period we cannot conclude that the calcium glycerophosphate supplement prevented lead absorption in this population. Copyright (c) 1999 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

CONTEXT: Poverty has been shown to be a determinant of health outcomes in many epidemiologic studies. OBJECTIVE: The goal of this study was to assess the association between household income and the mortality rate in cystic fibrosis (CF) patients. DESIGN, SETTING, AND PATIENTS: We selected white patients diagnosed before 18 years old and having 1 or more records in the Cystic Fibrosis Foundation Patient Registry since 1991. These 23 817 patients were linked to the 1990 US Census by their zip code of residence. The median household income was adjusted for state level differences in cost of living using the 1998 Consumer Price Index. INTERVENTIONS: None. MAIN OUTCOME MEASURES: We examined the association between categories of the median household income and the mortality rate. We examined the association between income categories and age-related changes in pulmonary function and body weight as well as specific nutritional and pulmonary therapies. RESULTS: We found a strong monotonic association between the median household income and the mortality rate. The test of trend was significant, and this effect was maintained after adjustment for a variety of patient and disease characteristics. When the lowest income category (<20 000 dollars) is compared with the highest (> or = 50 000 dollars), the adjusted incidence rates were 90.3 and 62.6 per 10 000 person years, respectively; this represents a 44% increased risk of death in the lowest income category. Patients living in areas with lower median household income also had consistently lower pulmonary function and body weight than did those living in higher income areas. The differences in weight percentiles and forced expiratory volume in 1 second are substantial in magnitude, they appear at an early age, and they persist into adulthood for these CF patients. Prescribed nutritional treatments and screening for CF-related diabetes were significantly higher among patients living in areas with lower median household income. Prescription of deoxyribonuclease and inhaled tobramycin was not significantly associated with median household income. CONCLUSION: There was a strong association between lower household income and increased mortality rate among CF patients. Additional understanding of this effect will require more complete and direct measurement of socioeconomic status and a better understanding of treatment adherence, local environmental conditions, and especially the care of CF patients during the early years of life. [ABSTRACT FROM AUTHOR]

Objectives: We sought to determine whether the changing practice of interventional cardiology has been associated with improved outcomes for women, and how these outcomes compare with those for men.Background: Previous work from the early 1990s suggested women are at a higher risk than men for adverse outcomes after percutaneous coronary interventions (PCIs). From 1994 to 1999 data were collected on 33,666 consecutive hospital admissions for a PCI in Northern New England. Multivariate models were used to adjust for differences in case-mix across year of procedure when comparing outcomes. Direct standardization was used to calculate adjusted rates.Results: From 1994 to 1999, the case-mix worsened for both women and men, although women had more co-morbidities than did men throughout the period. Stent use increased over time (>75% in 1999). Concomitantly, the need for emergency coronary artery bypass graft surgery (CABG) decreased significantly (p(trend) < or = 0.001; in 1999: 0.06% for women, 0.05% for men). Although the emergency CABG rates were higher for women at the beginning of the study, by the end, they were comparable (adjusted odds ratio 1.34, 95% confidence interval 0.76 to 2.38, p = 0.315). The myocardial infarction (MI) rates decreased over time for both women (by 29.7%, p(trend) = 0.378) and men (by 37.6%, p(trend) = 0.009) and did not differ by gender. The mortality rates did not decrease significantly over time and were not significantly different between the genders (mean 1.21% for women, 1.06% for men; p = 0.096).Conclusions: Concurrent with the changing practice of PCI, and despite treating sicker patients, there have been important improvements in post-PCI CABG and MI rates for women, as well as for men. Unlike in earlier years, there are no longer significant differences in outcomes by gender. [ABSTRACT FROM AUTHOR]

Rationale: Chronic lung diseases are associated with increased risk of mortality due to coronary heart disease (CHD). Nonetheless, the population attributable fraction (PAF) of lung function impairment relative to other established cardiovascular risk factors is unclear., Objective: To evaluate the PAF of low lung function for CHD mortality Methods: We harmonized and pooled lung function and clinical data across 8 US general population cohorts. Impaired lung function was defined as FEV 1 and/or FVC ≤95% predicted on baseline spirometry. The association between CHD mortality and risk factors was assessed using cause-specific proportional hazards and Fine-Gray proportional subdistribution hazards models, treating non-CHD mortality as a competing risk. Models were adjusted for lung function as well as age, sex, race/ethnicity, educational attainment, body mass index, smoking status, pack-years of smoking, diabetes mellitus, HDL, and high LDL (≥130 mg/dl). PAF was calculated as the relative change in the average absolute risk of ten-year CHD mortality by elimination of lung function lower than 95% predicted., Measurements and Main Results: Among 35143 participants, 1844 of 13174 (14.0%) deaths were due to CHD. Compared to FEV 1 pp >95%, the sub-distribution adjusted hazards ratio (95%CI) for low FEV 1pp was 1.30 (1.18-1.44). The PAF for FEV 1 pp≤95% was 12%, ranking low FEV 1 third in the list of PAF for CHD mortality, after hypertension and diabetes. Low FEV 1 pp ranked second in the subgroup of active smokers (PAF 14%), after hypertension., Conclusions: Low lung function, even in the range considered clinically normal, ranks high in the list of attributable risk factors for CHD mortality and should be considered in cardiovascular risk stratification.

The Human Epidemiology and Response to SARS-CoV-2 (HEROS) Study is a prospective, multicity, 6-month incidence study conducted from May 2020 to February 2021. The objectives were to identify risk factors for SARS-CoV-2 infection and household transmission among children and people with asthma and allergic diseases, and to use the host nasal transcriptome sampled longitudinally to understand infection risk and sequelae at the molecular level. To overcome challenges of clinical study implementation due to the coronavirus pandemic, this surveillance study used direct-to-participant methods to remotely enroll and prospectively follow eligible children who are participants in other National Institutes of Health-funded pediatric research studies and their household members. Households participated in weekly surveys and biweekly nasal sampling regardless of symptoms. The aim of this report is to widely share the methods and study instruments and to describe the rationale, design, execution, logistics, and characteristics of a large, observational, household-based, remote cohort study of SARS-CoV-2 infection and transmission in households with children. The study enrolled a total of 5598 individuals, including 1913 principal participants (children), 1913 primary caregivers, 729 secondary caregivers, and 1043 other household children. This study was successfully implemented without necessitating any in-person research visits and provides an approach for rapid execution of clinical research. Trial registration: ClinicalTrials.gov. Identifier: NCT04375761., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2024.)

Rationale: Body mass index (BMI) is associated with chronic obstructive pulmonary disease (COPD) mortality, but the underlying mechanisms are unclear. The effect of genetic variants aggregated into a polygenic score may elucidate the causal mechanisms and predict risk. Objectives: To examine the associations of genetically predicted BMI with all-cause and cause-specific mortality in COPD. Methods: We developed a polygenic score (PGS) for BMI (PGS BMI ) and tested for associations of the PGS BMI with all-cause, respiratory, and cardiovascular mortality in participants with COPD from the COPDGene (Genetic Epidemiology of COPD), ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points), and Framingham Heart studies. We calculated the difference between measured BMI and PGS-predicted BMI (BMI diff ) and categorized participants into groups of discordantly low (BMI diff <20th percentile), concordant (BMI diff between the 20th and 80th percentiles), and discordantly high (BMI diff >80th percentile) BMI. We applied Cox models, examined potential nonlinear associations of the PGS BMI and BMI diff with mortality, and summarized results with meta-analysis. Measurements and Main Results: We observed significant nonlinear associations of measured BMI and BMI diff , but not PGS BMI , with all-cause mortality. In meta-analyses, a one-standard deviation increase in the PGS BMI was associated with an increased hazard for cardiovascular mortality (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.12-1.49), but not for respiratory or all-cause mortality. Compared with participants with concordant measured and genetically predicted BMI, those with discordantly low BMI had higher risks for all-cause mortality (HR, 1.57; 95% CI, 1.41-1.74) and respiratory death (HR, 2.01; 95% CI, 1.61-2.51). Conclusions: In people with COPD, a higher genetically predicted BMI is associated with higher cardiovascular mortality but not respiratory mortality. Individuals with a discordantly low BMI have higher all-cause and respiratory mortality rates than those with a concordant BMI.