Expression of long non-coding RNAs in autoimmunity and linkage to enhancer function and autoimmune disease risk genetic variants.

Genome-wide association studies have identified numerous genetic variants conferring autoimmune disease risk. Most of these genetic variants lie outside protein-coding genes hampering mechanistic explorations. Numerous mRNAs are also differentially expressed in autoimmune disease but their regulation is also unclear. The majority of the human genome is transcribed yet its biologic significance is incompletely understood. We performed whole genome RNA-sequencing [RNA-seq] to categorize expression of mRNAs, known and novel long non-coding RNAs [lncRNAs] in leukocytes from subjects with autoimmune disease and identified annotated and novel lncRNAs differentially expressed across multiple disorders. We found that loci transcribing novel lncRNAs were not randomly distributed across the genome but co-localized with leukocyte transcriptional enhancers, especially super-enhancers, and near genetic variants associated with autoimmune disease risk. We propose that alterations in enhancer function, including lncRNA expression, produced by genetics and environment, change cellular phenotypes contributing to disease risk and pathogenesis and represent attractive therapeutic targets.

Insurance status and admission to hospital for head injuries: are we part of a two-tiered medical system?

Previous studies have shown an association between insurance status and use of resources for inpatient care. We sought to assess whether insurance status influences decisions regarding the evaluation and treatment of head injured patients in the emergency department (ED). Head injured patients were identified from ED data from 4 hospitals reporting to the Kentucky Emergency Medical Services Information System. Multiple regression analysis using admission, ED length of stay, and ED charges as outcome variables was then performed. From 216,137 ED visits there were 8,591 (4%) head injured patients identified from the database. Eliminating those with revisits, transfers to another hospital in the database, and isolated facial lacerations, there were 3,821 cases. Controlling for age, hospital, race, primary diagnosis, and indicators of severity of the injury, insurance status was significantly associated with hospital admission. Those uninsured were the least likely to be admitted (OR 0.41; 95% CI (0.31, 0.50), whereas those with public insurance had an intermediate probability (OR 0.50 95% CI (0.37, 0.68) as compared with those with private insurance. Similarly, ED charges were lower for Medicaid patients than insured patients ($880) and tended to be slightly lower for uninsured patients ($1,043) than insured patients ($1,141) (P =.001). Length of stay in the ED was shorter for publicly insured patients (179 minutes) than uninsured (186 minutes) and privately insured patients (192 minutes) (P =.001). The extent of evaluation and admission for head injured patients is associated with insurance status. This creates a dual standard of care for patients. Practitioners should work to standardize the evaluation of patients independent of paying status.

Economic costs of motor vehicle crashes involving teenaged drivers in Kentucky, 1994.

OBJECTIVES: To analyze data from motor vehicle crashes (MVCs) involving teenaged drivers in Kentucky for 1994, and derive cost estimates of these crashes. METHODS: Crash data were obtained from the Kentucky Traffic Accident Facts 1994 Report and the Kentucky Accident Reporting System. The National Highway Traffic Safety Administration's Crash-Cost program was used to generate cost estimates for Kentucky data. RESULTS: Teenaged drivers had significantly higher MVC fatal and non-fatal injury rates than did adult drivers. The deaths rates were 43.6 and 19.0 per 100,000 for teens and adult drivers, respectively. Odds ratios (ORs) were calculated to estimate the relative risk for (1) involvement in an MVC, (2) fatal or incapacitating injury, and (3) fatal injury for teenaged compared with adult drivers. The crude ORs were statistically significant at each age. Cost estimates were calculated on a per person/vehicle basis. A single fatal injury was $642,700. A critical injury was $563,000. In general, unit costs rose with increasing levels of injury severity. For the total number of fatal injuries, costs exceeded $91 million. For non-fatal injuries and property damage only crashes, total costs were $318 million. Overall, the total cost estimate for MVCs involving teenaged drivers was nearly $410 million. CONCLUSIONS: Strategies aimed to reduce the number of MVCs attributed to teenaged drivers should reduce both the number and costs of crash related deaths and injuries. Graduated driver licensing (GDL) systems are one plausible approach toward achieving this goal. By recently enacting a GDL system in Kentucky, it is anticipated that many lives and dollars will be saved.

The Kentucky Emergency Medical Services Information System: current progress and future goals.

The Kentucky Emergency Medical Services Information System was formed in 1993 to establish a centralized registry of prehospital and emergency department data. These data can aid individual providers in planning and providing patient services and state planners in systems development and disease surveillance. This article seeks to provide an overview of the system for providers of acute care services in Kentucky, its current capabilities and future goals.

Occupational fatalities in Kentucky--1994.

In Kentucky, seven out of nine industry groups exceed the national average fatality rates; in 1994, the agriculture/forestry/fishing industry rate of 80/ 100,000 was more than three times the national average. This paper describes the occupational fatality data collected during the first year of operation (1994) of the Fatality Assessment and Control Evaluation (FACE) Project in Kentucky. Investigators used multiple reporting sources to identify incidents, which were then systematically recorded and updated. On-site investigations were conducted for certain categories of fatalities. One hundred sixty-six occupational fatalities were recorded for 1994. Motor vehicle incidents were the most common cause of death, followed by machine-related incidents. Ages of victims ranged from 15 to 86 with a median of 46. Investigators completed 22 on-site visits during the period. In this article, descriptive statistics are presented, as well as suggestions for ways the medical community might contribute to the occupational fatality prevention effort.

Pediatric firearm-related fatalities. Not just an urban problem.

OBJECTIVE: To examine medical and demographic factors associated with the firearm-related deaths among children in Kentucky. DESIGN: Retrospective review and multiple regression analysis. DATA SOURCE: All firearm-related deaths among children younger than 20 years reported to the Kentucky Office of Vital Statistics, Frankfort, from 1988 to 1993. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All 320 pediatric firearm-related deaths that occurred in Kentucky from 1988 to 1993 were analyzed. Death rates were calculated for each county in the state. While the overall death rate from firearms was not significantly different between African-American and white children (relative risk [RR], 1.39; 95% confidence interval [CI], 0.98-1.98), the pattern of the types of events was markedly different. African American children were much more likely to have been involved in a homicide; suicides were more frequent in white children. Multiple Poisson regression analysis, controlling for age, race, and gender, identified only 1 variable that was significantly associated with deaths due to firearms. Children in rural Kentucky were at significantly more risk for a firearm-related death than children in urban areas (RR, 1.26; 95% CI, 1.01-1.62) even after controlling for medical system variables (availability of a hospital with 24-hour emergency services, availability of prehospital advanced life support, and availability of 911 service). CONCLUSIONS: Children in rural areas of Kentucky are at an increased risk for firearm-related mortality. Prevention and intervention programs that focus only on urban areas may not produce optimum results in the Kentucky setting. Further research is needed to determine factors that are important in rural areas so that interventions specific to them can be planned.

Factors associated with the higher traumatic death rate among rural children.

STUDY OBJECTIVE: To examine medical and demographic factors associated with traumatic deaths among children in Kentucky. METHODS: This was a retrospective review and multiple regression analysis of all deaths in children younger than 18 years reported to the Kentucky Office of Vital Statistics from 1988 to 1992. RESULTS: All 1,024 pediatric trauma deaths that occurred from 1988 to 1992 were analyzed. Death rates were calculated for each type of trauma for each county in the state. Motor vehicle accidents accounted for most of the pediatric deaths, but this finding was markedly age dependent. Death rates were higher in rural Kentucky for all forms of trauma and were highest in the Appalachian region. Multiple Poisson regression analysis identified variables associated with the traumatic pediatric death rates. Rural setting was associated with higher traumatic death rates, whereas the availability of a hospital with 24-hour emergency services in the county and the presence of advanced life support prehospital care were associated with lower death rates. Children in Appalachia were at an increased risk compared with other Kentucky children, even when we controlled for the rural nature of Appalachia. CONCLUSION: Demographic and medical system factors are associated with traumatic death rates in Kentucky children. Access to care and advanced prehospital support were both significantly associated with lower pediatric death rates. Increased access to quality care and training of prehospital providers in advanced life support should be priorities in the planning of trauma systems for this state.

Age and Pap smear history as a basis for intervention strategy.

As a means of developing effective intervention strategies for promoting Pap smear screening, we analyzed data from a population-based women's health survey (N = 603) in a 36-county area in southeastern Kentucky. The cervical cancer mortality rate for white women in this area is one of the highest in the United States. By using selected sociodemographic, health-care utilization, health knowledge, and health behavior variables in age-specific logistic regression models, we discriminated between women who had had a Pap smear within 3.5 years and those who had not. Several variables predicted Pap screening status regardless of the woman's age. Women of all age groups who had not been recently screened had encounters with the medical-care system. A key variable that affected use of screening services was ever use of birth control pills. The main differences between the three age groups were as follows: the 18-44 age group was less likely to see a private physician and less likely to seek medical care of any type, except for care related to pregnancy; only the 45-59 age group believed that cost of medical care was a problem; and only for the 60 or older age group were socioeconomic variables associated with not having recently had a Pap test.

Regional differences in death rates among postneonatal infants in Kentucky, 1982-1985.

Our objective was to analyze differences in postneonatal mortality rates between the southeastern (Appalachian) region of Kentucky and the remainder of the state to identify factors associated with increased mortality in the Appalachian (AP) region. The relative risk of postneonatal deaths in the AP region when compared with the remainder of Kentucky (KY) was 1.38 (95% confidence interval = 1.15-1.65). Adjustment for birth weight, maternal age, and marital status of the parents had no appreciable effect on the risk ratio; however, adjustment for maternal education negated the increased risk of postneonatal death among the AP region births. When causes of postneonatal death were compared, three specific disease groupings were disproportionately represented among AP infants: Sudden Infant Death Syndrome (SIDS); congenital malformations; and infections. Most striking was the excess risk of infection-related death because it represents a preventable component in the postneonatal mortality excess of the AP region; and, because of the apparent association with maternal "under education." These findings are discussed within a public health intervention context.

Infant death rates among the poor and nonpoor in Kentucky, 1982 to 1983.

The mortality rates of infants born in Kentucky during 1982 and 1983 were analyzed to determine whether there were differences between poor and nonpoor infants. We used computer matching with the Social Insurance Food Stamp files and with the Aid for Families With Dependent Children files to define poor and nonpoor Kentucky resident families. The crude death rate for poor infants was 13.7/1,000 births, and the nonpoor death rate was 10.8/1,000 births. After adjusting for several important variables, we found that the poor infant was at a significantly greater risk for death than the nonpoor infant but only during the postneonatal period (relative risk 2.04, P = .0003). Some differences by sex and race were noted. Sudden infant death syndrome and infections were largely responsible for the poor infants' higher postneonatal mortality risk.

Liquid chromatographic and ultraviolet spectrophotometric determination of bevantolol and hydrochlorothiazide in feeds.

Separate assay methods have been developed for the 2 components of an 80 + 20 drug blend of bevantolol and hydrochlorothiazide (HCT) in admixtures with animal feed. Drug/diet admixtures are extracted with methanol for reverse phase ion-pair liquid chromatographic (LC) assay of bevantolol, and with acetonitrile for ultraviolet spectrophotometric assay of HCT. Bevantolol, a cardioselective beta blocker, is separated from soluble feed components with an RP-18 column, using methanol-water-acetic acid (60 + 40 + 1) containing 0. 005M octane-sulfonic acid, sodium salt, as ion-pairing reagent. HCT is determined spectrophotometrically in acetonitrile extracts, using a suitable blank extract as reference. Average recovery of HCT from an admixture of 0.5 mg blend/g diet is 94.5% +/- 4.3 RSD and at 2.0 mg/g, 101.5% +/- 3.5 RSD. Bevantolol recovery from the same admixtures is 101.8% +/- 2.7 RSD and 99.0% +/- 3.5 RSD, respectively, using the method as described.

The search for medical care: an exploration of urban black behavior.

Results are presented of a study of the medical care-seeking behavior of black adult residents of lower and middle socioeconomic status in two predominantly black, yet geographically and socioeconomically distinct communities within the District of Columbia. Against a varied distribution of primary medical care opportunities within the District, substantial differences are demonstrated in their use by lower- and middle-status residents of a lower-class community. These differences are not, however, manifested among lower- and middle-status residents of an essentially middle-class neighborhood. The patterns of medical care-seeking behavior are observed within a framework of an almost total avoidance of the available medical care personnel and facilities in the proximate suburbs.