Trial of the MIND Diet for Prevention of Cognitive Decline in Older Persons.

BACKGROUND: Findings from observational studies suggest that dietary patterns may offer protective benefits against cognitive decline, but data from clinical trials are limited. The Mediterranean-DASH Intervention for Neurodegenerative Delay, known as the MIND diet, is a hybrid of the Mediterranean diet and the DASH (Dietary Approaches to Stop Hypertension) diet, with modifications to include foods that have been putatively associated with a decreased risk of dementia. METHODS: We performed a two-site, randomized, controlled trial involving older adults without cognitive impairment but with a family history of dementia, a body-mass index (the weight in kilograms divided by the square of the height in meters) greater than 25, and a suboptimal diet, as determined by means of a 14-item questionnaire, to test the cognitive effects of the MIND diet with mild caloric restriction as compared with a control diet with mild caloric restriction. We assigned the participants in a 1:1 ratio to follow the intervention or the control diet for 3 years. All the participants received counseling regarding adherence to their assigned diet plus support to promote weight loss. The primary end point was the change from baseline in a global cognition score and four cognitive domain scores, all of which were derived from a 12-test battery. The raw scores from each test were converted to z scores, which were averaged across all tests to create the global cognition score and across component tests to create the four domain scores; higher scores indicate better cognitive performance. The secondary outcome was the change from baseline in magnetic resonance imaging (MRI)-derived measures of brain characteristics in a nonrandom sample of participants. RESULTS: A total of 1929 persons underwent screening, and 604 were enrolled; 301 were assigned to the MIND-diet group and 303 to the control-diet group. The trial was completed by 93.4% of the participants. From baseline to year 3, improvements in global cognition scores were observed in both groups, with increases of 0.205 standardized units in the MIND-diet group and 0.170 standardized units in the control-diet group (mean difference, 0.035 standardized units; 95% confidence interval, -0.022 to 0.092; P = 0.23). Changes in white-matter hyperintensities, hippocampal volumes, and total gray- and white-matter volumes on MRI were similar in the two groups. CONCLUSIONS: Among cognitively unimpaired participants with a family history of dementia, changes in cognition and brain MRI outcomes from baseline to year 3 did not differ significantly between those who followed the MIND diet and those who followed the control diet with mild caloric restriction. (Funded by the National Institute on Aging; ClinicalTrials.gov number, NCT02817074.).

Preschool impulse oscillometry predicts active asthma and impaired lung function at school age.

BACKGROUND: Asthmatic symptoms often start during early childhood. Impulse oscillometry (IOS) is feasible in preschool children who may be unable to reliably perform spirometry measurements. OBJECTIVE: We sought to evaluate the use of IOS in a multicenter, multiethnic high-risk asthma cohort titled the Vitamin D Antenatal Asthma Reduction Trial. METHODS: The trial recruited pregnant women whose children were followed from birth to age 8 years. Lung function was assessed with IOS at ages 4, 5, and 6 years and spirometry at ages 5, 6, 7, and 8 years. Asthma status, respiratory symptoms, and medication use were assessed with repeated questionnaires from birth to age 8 years. RESULTS: In total, 220 children were included in this secondary analysis. Recent respiratory symptoms and short-acting ß2-agonist use were associated with increased respiratory resistance at 5 Hz at age 4 years (ß = 2.6; 95% CI, 1.0 to 4.4; P = .002 and ß = 3.4; 95% CI, 0.7 to 6.2; P = .015, respectively). Increased respiratory resistance at 5 Hz at age 4 years was also associated with decreased lung function from ages 5 to 8 years (ß = -0.3; 95% CI, -0.5 to -0.1; P < .001 for FEV1 at 8 years) and active asthma at age 8 years (ß = 2.0; 95% CI, 0.2 to 3.8; P = .029). CONCLUSIONS: Increased respiratory resistance in preschool IOS is associated with frequent respiratory symptoms as well as school-age asthma and lung function impairment. Our findings suggest that IOS may serve as a potential objective measure for early identification of children who are at high risk of respiratory morbidity.

Maternal vitamin D status modifies the effects of early life tobacco exposure on child lung function.

BACKGROUND: Prior studies suggest that vitamin D may modify the effects of environmental exposures; however, none have investigated gestational vitamin D and cumulative tobacco smoke exposure (TSE) throughout pregnancy and early life. OBJECTIVES: This study investigated the effects of early life TSE on child lung function and the modulatory effects of gestational vitamin D on this association. METHODS: The VDAART (Vitamin D Antenatal Asthma Reduction Trial) recruited nonsmoking pregnant women and followed the mother-child pairs to age 6 years. TSE was assessed with questionnaires and plasma cotinine measurements in the mothers (10-18 and 32-38 gestational weeks) and children (1, 3, and 6 years). Cumulative TSE was calculated from the repeated cotinine measurements. 25-hydroxyvitamin D (25[OH]D) levels were measured at 10-18 and 32-38 gestational weeks. Lung function was assessed at 6 years with spirometry and impulse oscillometry. RESULTS: Of the 476 mother-child pairs, 205 (43%) had increased cotinine levels at ≥1 time point. Cumulative TSE was associated with decreased FEV1 (ß = -0.043 L, P = .018) and increased respiratory resistance at 5 Hz (R5; ß = 0.060 kPa/L/s, P = .002). This association persisted in subjects with insufficient (<30 ng/mL) 25(OH)D levels throughout pregnancy (ß = 0.077 kPa/L/s, P = .016 for R5) but not among those with sufficient levels throughout pregnancy. CONCLUSIONS: Cumulative TSE from pregnancy to childhood is associated with dose- and duration-dependent decreases in child lung function at 6 years even in the absence of reported maternal smoking. Gestational vitamin D may modulate this effect and have therapeutic potential for minimizing the adverse effect of TSE on lung throughout early life. RANDOMIZED TRIAL: Maternal Vitamin D Supplementation to Prevent Childhood Asthma (VDAART); clinicaltrials.gov identifier: NCT00920621.

Six-Year Follow-up of a Trial of Antenatal Vitamin D for Asthma Reduction.

BACKGROUND: We previously reported the results of a trial of prenatal vitamin D supplementation to prevent asthma and recurrent wheeze in young children, which suggested that supplementation provided a protective effect at the age of 3 years. We followed the children through the age of 6 years to determine the course of asthma and recurrent wheeze. METHODS: In this follow-up study, investigators and participants remained unaware of the treatment assignments through the children's sixth birthday. We aimed to determine whether, when maternal levels of 25-hydroxyvitamin D were taken into account, children born to mothers who had received 4400 IU of vitamin D3 per day during pregnancy (vitamin D group) would have a lower incidence of asthma and recurrent wheeze at the age of 6 years than would those born to mothers who had received 400 IU of vitamin D3 per day (control group). Time-to-event methods were used to compare the treatment groups with respect to time to the onset of asthma or recurrent wheeze. Multivariate methods were used to compare longitudinal measures of lung function between the treatment groups. RESULTS: There was no effect of maternal vitamin D supplementation on asthma and recurrent wheeze in either an intention-to-treat analysis or an analysis with stratification according to the maternal 25-hydroxyvitamin D level during pregnancy. There was no effect of prenatal vitamin D supplementation on most of the prespecified secondary outcomes. We found no effects of prenatal supplementation on spirometric indexes. Although there was a very small effect on airway resistance as measured by impulse oscillometry, this finding was of uncertain significance. CONCLUSIONS: Vitamin D supplementation during the prenatal period alone did not influence the 6-year incidence of asthma and recurrent wheeze among children who were at risk for asthma. (Funded by the National Heart, Lung, and Blood Institute; VDAART ClinicalTrials.gov number, NCT00920621.).

Low gestational vitamin D level and childhood asthma are related to impaired lung function in high-risk children.

BACKGROUND: Lung function impairment in early life often persists into adulthood. Therefore, identifying risk factors for low childhood lung function is crucial. OBJECTIVE: We examined the effect of 25-hydroxyvitamin D (25[OH]D) level and childhood asthma phenotype on childhood lung function in the Vitamin D Antenatal Asthma Reduction Trial (VDAART). METHODS: The 25(OH)D level was measured at set time points in mothers during pregnancy and in children during early life. On the basis of parental reports, children were categorized into 3 clinical phenotypes: asymptomatic/infrequent wheeze, early transient wheeze, and asthma at age 6 years. Lung function was assessed with impulse oscillometry at ages 4, 5, and 6 years and with spirometry at ages 5 and 6 years. RESULTS: A total of 570 mother-child pairs were included in this post hoc analysis. Mean gestational 25(OH)D-level quartiles were negatively associated with child respiratory resistance at 5 Hz (R5) from age 4 to 6 years (ß, -0.021 kPa/L/s; 95% CI, -0.035 to -0.007; P = .003) and positively associated with FEV1 (ß, 0.018 L; 95% CI, 0.005-0.031; P = .008) and forced vital capacity (ß, 0.022 L; 95% CI, 0.009-0.036; P = .002) from age 5 to 6 years. Children with asthma at age 6 years had lower lung function from age 4 to 6 years than the asymptomatic/infrequent wheeze group (ß, 0.065 kPa/L/s; 95% CI, 0.028 to 0.102; P < .001 for R5 and ß, -0.063 L; 95% CI, -0.099 to -0.028; P < .001 for FEV1). CONCLUSIONS: Low gestational 25(OH)D level and childhood asthma are important risk factors for decreased lung function in early childhood.

The use of high definition colonoscopy versus standard definition: does it affect polyp detection rate?

BACKGROUND: Polyp detection rate (PDR) during lower gastrointestinal endoscopy (LGIE) is of clinical importance. Detecting adenomatous polyps early in the adenoma-carcinoma sequence can halt disease progression, enabling treatment at a favourable stage. High definition colonoscopy (HDC) has been used in our hospital alongside standard definition equipment since 2011. We aim to determine what affect the use of HDC has on PDR. METHODS: Post-hoc analysis of a prospectively maintained database on all patients undergoing LGIE was performed (01/01/2012-31/12/2015), n = 15,448. Analysis tested the primary outcome of HD's effect on PDR across LGIE and secondary outcome stratified this by endoscopist group (Physician (PE), Surgeon (SE) and Nurse Endoscopist (NE)). RESULTS: Of 15,448 patients, 1353 underwent HDC. Unmatched analysis showed PDR increased by 5.3% in this group (p < 0.001). Matched analysis considered 2288 patients from the total cohort (1144 HDC) and showed an increase of 1% in PDR with HDC (p = 0.578). Further unmatched analysis stratified by endoscopist groups showed a PDR increase of 1.8% (p = 0.375), 5.4% (p = 0.008) and 4.6% (p = 0.021) by PE, SE and NE respectively. Matched analysis demonstrated an increase of 1% (p = 0.734) and 1.5% (p = 0.701) amongst PE and NE, with a decrease of 0.6% (p = 0.883) by SE. CONCLUSION: The introduction of HDC increased PDR across all LGIE in our hospital, though this was not clinically significant. This marginal benefit was present across all endoscopist groups with no group benefiting over another in matched analysis.

Impacts of extreme heat on emergency medical service calls in King County, Washington, 2007-2012: relative risk and time series analyses of basic and advanced life support.

BACKGROUND: Exposure to excessive heat kills more people than any other weather-related phenomenon, aggravates chronic diseases, and causes direct heat illness. Strong associations between extreme heat and health have been identified through increased mortality and hospitalizations and there is growing evidence demonstrating increased emergency department visits and demand for emergency medical services (EMS). The purpose of this study is to build on an existing regional assessment of mortality and hospitalizations by analyzing EMS demand associated with extreme heat, using calls as a health metric, in King County, Washington (WA), for a 6-year period. METHODS: Relative-risk and time series analyses were used to characterize the association between heat and EMS calls for May 1 through September 30 of each year for 2007-2012. Two EMS categories, basic life support (BLS) and advanced life support (ALS), were analyzed for the effects of heat on health outcomes and transportation volume, stratified by age. Extreme heat was model-derived as the 95th (29.7 °C) and 99th (36.7 °C) percentile of average county-wide maximum daily humidex for BLS and ALS calls respectively. RESULTS: Relative-risk analyses revealed an 8 % (95 % CI: 6-9 %) increase in BLS calls, and a 14 % (95 % CI: 9-20 %) increase in ALS calls, on a heat day (29.7 and 36.7 °C humidex, respectively) versus a non-heat day for all ages, all causes. Time series analyses found a 6.6 % increase in BLS calls, and a 3.8 % increase in ALS calls, per unit-humidex increase above the optimum threshold, 40.7 and 39.7 °C humidex respectively. Increases in "no" and "any" transportation were found in both relative risk and time series analyses. Analysis by age category identified significant results for all age groups, with the 15-44 and 45-64 year old age groups showing some of the highest and most frequent increases across health conditions. Multiple specific health conditions were associated with increased risk of an EMS call including abdominal/genito-urinary, alcohol/drug, anaphylaxis/allergy, cardiovascular, metabolic/endocrine, diabetes, neurological, heat illness and dehydration, and psychological conditions. CONCLUSIONS: Extreme heat increases the risk of EMS calls in King County, WA, with effects demonstrated in relatively younger populations and more health conditions than those identified in previous analyses.

Impact of Building Height and Volume on Cardiac Arrest Response Time.

Emergency medical services (EMS) care may be delayed when out-of-hospital cardiac arrest (OHCA) occurs in tall or large buildings. We hypothesized that larger building height and volume were related to a longer curb-to-defibrillator activation interval. We retrospectively evaluated 3,065 EMS responses to OHCA in a large city between 2003-13 that occurred indoors, prior to EMS arrival, and without prior deployment of a defibrillator. The two-tiered EMS system uses automated external defibrillator-equipped basic life support firefighters followed by paramedics dispatched from a single call center. We calculated three time intervals obtained from the computerized dispatch report and time-synchronized defibrillators: initial 911 call to address curb arrival by first unit (call-to-curb), curb arrival to defibrillator power on (curb-to-defib on), and the combined call-to-defib on interval. Building height and surface area were measured with a validated program based on aerial photography. Buildings were categorized by height as short (<25 ft), medium (26-64 ft) and tall (>64 ft). Volume was categorized as small (<60,000 ft(3)), midsize (60,000-1,202,600 ft(3)) and large (>1,202,600 ft(3)). Intervals were compared using the two-tailed Mann-Whitney test. EMS responded to 1,673 OHCA events in short, 1,134 in medium, and 258 in tall buildings. There was a 1.14 minute increase in median curb-to-defib on interval from 1.97 in short to 3.11 minutes in tall buildings (p < 0.01). Taller buildings, however, had a shorter call-to-curb interval (4.73 for short vs 3.96 minutes for tall, p < 0.01), such that the difference in call-to-defib on interval was only 0.27 minutes: 6.87 for short and 7.14 for tall buildings. A similar relationship was observed for small-volume compared to large-volume building: longer curb-to-AED (1.90 vs. 3.01 minutes, p < 0.01), but shorter call-to-curb (4.87 vs. 4.05, p < 0.01); the difference in call-to-defib on was 0.18 minutes. Both taller and larger-volume buildings had longer curb-to-AED intervals but shorter 911 call-to-curb arrival intervals. As a consequence, building height and volume had a modest overall relationship with interval from call to defibrillator application. These results do not support the hypothesis that either taller or larger-volume buildings need cause poorer outcomes in urban environments.

Dispatcher-assisted cardiopulmonary resuscitation: time to identify cardiac arrest and deliver chest compression instructions.

BACKGROUND: Dispatcher-assisted cardiopulmonary resuscitation (DA-CPR), in which 9-1-1 dispatchers provide CPR instructions over the telephone, has been shown to nearly double the rate of bystander CPR. We sought to identify factors that hampered the identification of cardiac arrest by 9-1-1 dispatchers and prevented or delayed the provision of dispatcher-assisted CPR chest compressions. METHODS AND RESULTS: We reviewed dispatch recordings for 476 out-of-hospital cardiac arrests occurring between January 1, 2011, and December 31, 2011. We found that the dispatcher correctly identified cardiac arrest in 80% of reviewed cases and 92% of cases in which they were able to assess patient consciousness and breathing. The median time to recognition of the arrest was 75 seconds. Chest compressions following dispatcher-assisted CPR instructions occurred in 62% of cases when the dispatcher had the opportunity to asses for consciousness and breathing and bystander CPR was not already started. The median time to first dispatcher-assisted CPR chest compression was 176 seconds. CONCLUSIONS: Dispatchers are able to accurately diagnose cardiac arrest over the telephone, but recognition is likely not possible in all circumstances. In some cases, recognition of cardiac arrest may be improved through training in the detection of agonal respirations. Delays in the delivery of dispatcher-assisted CPR chest compressions are common and are attributable to a mixture of dispatcher behavior and factors beyond the control of the dispatcher. Performance standards for the successful and quick recognition of cardiac arrest and delivery of first chest compressions should be adopted as metrics against which emergency medical services systems can measure their performance.

Factors associated with the adoption of a patient education intervention among first responders, King County, Washington, 2010-2011.

INTRODUCTION: This study investigated facilitators and barriers to adoption of an at-scene patient education program by firefighter emergency medical technicians (EMTs) in King County, Washington. METHODS: We consulted providers of emergency medical services (EMS) to develop a patient education pamphlet in the form of a tear-off sheet that could be attached to the EMT medical incident report. The pamphlet included resources for at-scene patient education on high blood pressure, blood glucose, falls, and social services. The program was launched in 29 fire departments in King County, Washington, on January 1, 2010, and a formal evaluation was conducted in late 2011. We developed a survey based on diffusion theory to assess 1) awareness of the pamphlet, 2) evaluation of the pamphlet attributes, 3) encouragement by peers and superiors for handing out the pamphlet, 4) perceived behavioral norms, and 5) demographic variables associated with self-reported adoption of the at-scene patient education program. The survey was completed by 822 (40.1%) of 2,047 firefighter emergency medical technicians. We conducted bivariate and multivariable analyses to assess associations between independent variables and self-reported adoption of the program. RESULTS: Adoption of the at-scene patient education intervention was significantly associated with positive evaluation of the pamphlet, encouragement from peers and superiors, and perceived behavioral norms. EMS providers reported they were most likely to hand out the pamphlet to patients in private residences who were treated and left at the scene. CONCLUSION: Attributes of chronic disease prevention programs and encouragement from peers and supervisors are necessary in diffusion of patient education interventions in the prehospital care setting.

Incidence, causes, and survival trends from cardiovascular-related sudden cardiac arrest in children and young adults 0 to 35 years of age: a 30-year review.

BACKGROUND: Sudden cardiac arrest is a leading cause of death in children and young adults. This study determined the incidence, cause, and outcomes of cardiovascular-related out-of-hospital cardiac arrest (OHCA) in individuals <35 years of age. METHODS AND RESULTS: A retrospective cohort of OHCA in children and young adults from 1980 through 2009 was identified from the King County (Washington) Division of Emergency Medical Services' Cardiac Arrest Database. Incidence was calculated from population census data and causes of arrest determined by review of autopsy reports and all available medical records. A total of 361 cases (26 cases 0-2 years of age, 30 cases 3-13 years of age, 60 cases 14-24 years of age, and 245 cases 25-35 years of age) of OHCA were treated by emergency medical services responders, for an overall incidence of 2.28 per 100 000 person-years (2.1 in those 0-2 years of age, 0.61 in those 3-13 years of age, 1.44 in those 14-24 years of age, and 4.40 in those 25-35 years of age). The most common causes of OHCA were congenital abnormalities in those 0 to 2 years of age (84.0%) and 3 to 13 years of age (21%), presumed primary arrhythmia in those 14 to 24 of age (23.5%), and coronary artery disease in those 25 to 35 years of age (42.9%). The overall survival rate was 26.9% (3.8% in those 0-2 years of age, 40.0% in those 3-13 years of age, 36.7% in those 14-24 years of age, and 27.8% in those 25-35 years of age). Survival increased throughout the study period from 13.0% in 1980 to 1989 to 40.2% in 2000 to 2009 (P<0.001). CONCLUSIONS: The incidence of OHCA in children and young adults is higher than previously reported, and a more specific understanding of the causes should guide future prevention programs. Survival trends support contemporary resuscitation protocols for OHCA in the young.

Impact of changes in resuscitation practice on survival and neurological outcome after out-of-hospital cardiac arrest resulting from nonshockable arrhythmias.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) claims millions of lives worldwide each year. OHCA survival from shockable arrhythmias (ventricular fibrillation/ tachycardia) improved in several communities after implementation of American Heart Association resuscitation guidelines that eliminated "stacked" shocks and emphasized chest compressions. "Nonshockable" rhythms are now the predominant presentation of OHCA; the benefit of such treatments on nonshockable rhythms is uncertain. METHODS AND RESULTS: We studied 3960 patients with nontraumatic OHCA from nonshockable initial rhythms treated by prehospital providers in King County, Washington, over a 10-year period. Outcomes during a 5-year intervention period after adoption of new resuscitation guidelines were compared with the previous 5-year historical control period. The primary outcome was 1-year survival. Patient demographics and resuscitation characteristics were similar between the control (n=1774) and intervention (n=2186) groups, among whom 471 of 1774 patients (27%) versus 742 of 2186 patients (34%), respectively, achieved return of spontaneous circulation; 82 (4.6%) versus 149 (6.8%) were discharged from hospital, 60 (3.4%) versus 112 (5.1%) with favorable neurological outcome; 73 (4.1%) versus 135 (6.2%) survived 1 month; and 48 (2.7%) versus 106 patients (4.9%) survived 1 year (all P≤0.005). After adjustment for potential confounders, the intervention period was associated with an improved odds of 1.50 (95% confidence interval, 1.29-1.74) for return of spontaneous circulation, 1.53 (95% confidence interval, 1.14-2.05) for hospital survival, 1.56 (95% confidence interval, 1.11-2.18) for favorable neurological status, 1.54 (95% confidence interval, 1.14-2.10) for 1-month survival, and 1.85 (95% confidence interval, 1.29-2.66) for 1-year survival. CONCLUSION: Outcomes from OHCA resulting from nonshockable rhythms, although poor by comparison with shockable rhythm presentations, improved significantly after implementation of resuscitation guideline changes, suggesting their potential to benefit all presentations of OHCA.

Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) study: Rationale, design and baseline characteristics of a randomized control trial of the MIND diet on cognitive decline.

Alzheimer's dementia (AD) is the sixth leading cause of death in the U.S., with an estimated $305 billion cost of care in 2020. Currently there are no cures or therapies to ameliorate the disease progression and symptoms. Growing evidence links a diet characterized by high antioxidant components with benefits to cognitive function, which is indicative of the preventative potential of dietary inteventions. The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) study is a 3-year, multicenter, randomized controlled trial to test the effects of the MIND diet on cognitive function in 604 individuals at risk for AD. Men and women ages 65 to 84 years were recruited. Eligible participants were randomized to either the MIND diet with mild caloric restriction or their usual diet with mild caloric restriction. Cognitive assessments, medical history, blood pressure, anthropometric measurements, and blood and urine sample collections will be taken at baseline and follow-up visits. MRI scans will be completed on approximately half of the enrolled participants at the start and end of the study. Unique features of the MIND study include: 1) a dietary pattern, rather than single nutrient or food, tested in an at-risk population; 2) foods featured as key components of the MIND diet (i.e. extra-virgin olive oil, blueberries, and nuts) provided for participants; and 3) MRI scans of brain structure and volume that may provide potential mechanistic evidence on the effects of the diet. Results from the study will be crucial to the development of dietary guidelines for the prevention of AD.

Global Alliance for Genomics and Health Meets Bioconductor: Toward Reproducible and Agile Cancer Genomics at Cloud Scale.

PURPOSE: Institutional efforts toward the democratization of cloud-scale data and analysis methods for cancer genomics are proceeding rapidly. As part of this effort, we bridge two major bioinformatic initiatives: the Global Alliance for Genomics and Health (GA4GH) and Bioconductor. METHODS: We describe in detail a use case in pancancer transcriptomics conducted by blending implementations of the GA4GH Workflow Execution Services and Tool Registry Service concepts with the Bioconductor curatedTCGAData and BiocOncoTK packages. RESULTS: We carried out the analysis with a formally archived workflow and container at dockstore.org and a workspace and notebook at app.terra.bio. The analysis identified relationships between microsatellite instability and biomarkers of immune dysregulation at a finer level of granularity than previously reported. Our use of standard approaches to containerization and workflow programming allows this analysis to be replicated and extended. CONCLUSION: Experimental use of dockstore.org and app.terra.bio in concert with Bioconductor enabled novel statistical analysis of large genomic projects without the need for local supercomputing resources but involved challenges related to container design, script archiving, and unit testing. Best practices and cost/benefit metrics for the management and analysis of globally federated genomic data and annotation are evolving. The creation and execution of use cases like the one reported here will be helpful in the development and comparison of approaches to federated data/analysis systems in cancer genomics.

Socioeconomic status is associated with provision of bystander cardiopulmonary resuscitation.

OBJECTIVE: Although socioeconomic status (SES) has been linked to multiple health outcomes, there have been few studies of the effect of SES on the provision of bystander cardiopulmonary resuscitation (CPR) during cardiac arrest events and no studies that we know of on the effect of SES on the provision of dispatcher-assisted bystander CPR. This study sought to define the relationship between SES and the provision of bystander CPR in an emergency medical system that includes dispatcher-provided CPR instructions. METHODS: This study was a retrospective, cohort analysis of cardiac arrests due to cardiac causes occurring in private residences in King County, Washington, from January 1, 1999, to December 31, 2005. We used the tax-assessed value of the location of the cardiac arrest as an estimate of the SES of potential bystanders as well as multiple measures from 2000 Census data (education, employment, median household income, and race/ethnicity). We also examined the effect of patient and system characteristics that may affect the provision of bystander CPR. Logistic regression models were used to analyze the association of these factors with two outcomes: the provision of bystander CPR with and without dispatcher assistance. RESULTS: Forty-four percent (1,151/2,618) of cardiac arrest victims received bystander CPR. Four hundred fifty-seven people (17.5% of the entire study population, 39.7% of those who received any bystander CPR) received CPR without telephone instructions. A total of 694 people received dispatcher-assisted bystander CPR (25.6% of the entire population, 60.4% of those receiving any bystander CPR). After adjusting for demographic and care factors, we found a strong association between the tax-assessed value of the cardiac arrest location and increased odds of the provision of bystander CPR without dispatcher instructions and bystander CPR with dispatcher assistance compared with no bystander CPR. CONCLUSIONS: This study suggests that higher bystander SES is associated with increased rates of bystander CPR with and without dispatcher instructions. CPR training programs that target lower-SES communities and assessment of these training methods may be warranted.

TFutils: Data structures for transcription factor bioinformatics.

DNA transcription is intrinsically complex. Bioinformatic work with transcription factors (TFs) is complicated by a multiplicity of data resources and annotations. The Bioconductor package TFutils includes data structures and functions to enhance the precision and utility of integrative analyses that have components involving TFs. TFutils provides catalogs of human TFs from three reference sources (CISBP, HOCOMOCO, and GO), a catalog of TF targets derived from MSigDb, and multiple approaches to enumerating TF binding sites, including an interface to results of 690 ENCODE experiments. Aspects of integration of TF binding patterns and genome-wide association study results are explored in examples.

Intraosseous compared to intravenous drug resuscitation in out-of-hospital cardiac arrest.

AIMS: Although the intraosseous (IO) route is increasingly used for vascular access in out-of-hospital cardiac arrest (OHCA), little is known about its comparative effectiveness relative to intravenous (IV) access. We evaluated clinical outcomes following OHCA comparing drug administration via IO versus IV routes. METHODS: This retrospective cohort study evaluated Emergency Medical Services (EMS)-treated adults with atraumatic OHCA in a large metropolitan EMS system between 9/1/2012-12/31/2014. Access was classified as IO or IV based on the route of first EMS drug administration. Study endpoints were survival to hospital discharge, return of spontaneous circulation (ROSC) and survival to hospital admission. RESULTS: Among 2164 adults with OHCA, 1800 met eligibility criteria, 1525 of whom were treated via IV and 275 principally via tibial-IO routes. Compared to IV, IO-treated patients were younger, more often women, had unwitnessed OHCA, a non-cardiac aetiology, and presented with non-shockable rhythms. IO versus IV-treated patients were less likely to survive to hospital discharge (14.9% vs 22.8%, p=0.003), achieve ROSC (43.6% vs 55.5%, p<0.001) or be hospitalized (38.5% vs 50.0% p<0.001). In multivariable adjusted analyses, IO treatment was not associated with survival to discharge (odds ratio (OR) (95% confidence interval) 0.81 (0.55, 1.21), p=0.31), but was associated with a lower likelihood of ROSC (OR=0.67 (0.50, 0.88), p=0.004) and survival to hospitalization (OR=0.68 (0.51, 0.91), p=0.009). CONCLUSION: Though not independently associated with survival to discharge, principally tibial IO versus IV treatment was associated with a lower likelihood of ROSC and hospitalization. How routes of vascular access influence clinical outcomes after OHCA merits additional study.

Determining witnessed status for out-of-hospital cardiac arrest.

OBJECTIVE: Witnessed status is considered a core variable in reporting cardiac arrest data and can be ascertained from either the emergency dispatch recording or the pre-hospital record. The purpose of this study is to compare and assess the quality and consistency of these information sources. METHODS: This retrospective analysis included 1896 cases of out-of-hospital cardiac arrest occurring between September 1, 2012 and December 31, 2014. RESULTS: We found that there was minimal (kappa=0.30, 95% CI 0.27-0.33) to moderate (kappa=0.64, 95% CI 0.59-0.69) agreement between the pre-hospital record and the emergency dispatch recording when these sources of information are used to determine witnessed status. Witnessed status could not be determined from the emergency dispatch recording in 36.2% (n=684) of eligible cases. Survival was similar regardless of the method used to determine witnessed status. Using a combination of the pre-hospital record and the emergency dispatch recording yielded the highest number of witnessed cases. CONCLUSION: The determination of witnessed status in out-of-hospital cardiac arrest may be challenging, as evidenced by the discrepancies in witnessed status when comparing different sources of information. The large number of cases where the witnessed status could not be determined from the emergency dispatch recording precludes its use as the sole source of information. It is reasonable to use the patient care record alone, however it should be recognized that there is misclassification of witnessed status regardless of the method used and this may affect the strength of association between witnessed status and survival.

Coordinating Care for Falls via Emergency Responders: A Feasibility Study of a Brief At-Scene Intervention.

Falls account for a substantial portion of 9-1-1 calls, but few studies have examined the potential for an emergency medical system role in fall prevention. We tested the feasibility and effectiveness of an emergency medical technician (EMT)-delivered, at-scene intervention to link elders calling 9-1-1 for a fall with a multifactorial fall prevention program in their community. The intervention was conducted in a single fire department in King County, Washington and consisted of a brief public health message about the preventability of falls and written fall prevention program information left at scene. Data sources included 9-1-1 reports, telephone interviews with intervention department fallers and sociodemographically comparable fallers from three other fire departments in the same county, and in-person discussions with intervention department EMTs. Interviews elicited faller recall and perceptions of the intervention, EMT perceptions of intervention feasibility, and resultant referrals. Sixteen percent of all 9-1-1 calls during the intervention period were for falls. The intervention was delivered to 49% of fallers, the majority of whom (75%) were left at scene. Their mean age (N = 92) was 80 ± 8 years; 78% were women, 39% had annual incomes under $20K, and 34% lived alone. Thirty-five percent reported that an EMT had discussed falls and fall prevention (vs. 8% of comparison group, P < 0.01); 84% reported that the information was useful. Six percent reported having made an appointment with a fall prevention program (vs. 3% of comparison group). EMTs reported that the intervention was worthwhile and did not add substantially to their workload. A brief, at-scene intervention is feasible and acceptable to fallers and EMTs. Although it activates only a small percent to seek out fall prevention programs, the public health impact of this low-cost strategy may be substantial.

Expression Quantitative Trait Loci Information Improves Predictive Modeling of Disease Relevance of Non-Coding Genetic Variation.

Disease-associated loci identified through genome-wide association studies (GWAS) frequently localize to non-coding sequence. We and others have demonstrated strong enrichment of such single nucleotide polymorphisms (SNPs) for expression quantitative trait loci (eQTLs), supporting an important role for regulatory genetic variation in complex disease pathogenesis. Herein we describe our initial efforts to develop a predictive model of disease-associated variants leveraging eQTL information. We first catalogued cis-acting eQTLs (SNPs within 100 kb of target gene transcripts) by meta-analyzing four studies of three blood-derived tissues (n = 586). At a false discovery rate < 5%, we mapped eQTLs for 6,535 genes; these were enriched for disease-associated genes (P < 10(-04)), particularly those related to immune diseases and metabolic traits. Based on eQTL information and other variant annotations (distance from target gene transcript, minor allele frequency, and chromatin state), we created multivariate logistic regression models to predict SNP membership in reported GWAS. The complete model revealed independent contributions of specific annotations as strong predictors, including evidence for an eQTL (odds ratio (OR) = 1.2-2.0, P < 10(-11)) and the chromatin states of active promoters, different classes of strong or weak enhancers, or transcriptionally active regions (OR = 1.5-2.3, P < 10(-11)). This complete prediction model including eQTL association information ultimately allowed for better discrimination of SNPs with higher probabilities of GWAS membership (6.3-10.0%, compared to 3.5% for a random SNP) than the other two models excluding eQTL information. This eQTL-based prediction model of disease relevance can help systematically prioritize non-coding GWAS SNPs for further functional characterization.