Advancing genomics to improve health equity.

Health equity is the state in which everyone has fair and just opportunities to attain their highest level of health. The field of human genomics has fallen short in increasing health equity, largely because the diversity of the human population has been inadequately reflected among participants of genomics research. This lack of diversity leads to disparities that can have scientific and clinical consequences. Achieving health equity related to genomics will require greater effort in addressing inequities within the field. As part of the commitment of the National Human Genome Research Institute (NHGRI) to advancing health equity, it convened experts in genomics and health equity research to make recommendations and performed a review of current literature to identify the landscape of gaps and opportunities at the interface between human genomics and health equity research. This Perspective describes these findings and examines health equity within the context of human genomics and genomic medicine.

Effect of a Digital Health Intervention on Receipt of Colorectal Cancer Screening in Vulnerable Patients: A Randomized Controlled Trial.

Background: Screening for colorectal cancer (CRC) reduces mortality, yet more than one third of age-eligible Americans are unscreened. Objective: To examine the effect of a digital health intervention, Mobile Patient Technology for Health-CRC (mPATH-CRC), on rates of CRC screening. Design: Randomized clinical trial. (ClinicalTrials.gov: NCT02088333). Setting: 6 community-based primary care practices. Participants: 450 patients (223 in the mPATH-CRC group and 227 in usual care) scheduled for a primary care visit and due for routine CRC screening. Intervention: An iPad application that displays a CRC screening decision aid, lets patients order their own screening tests, and sends automated follow-up electronic messages to support patients. Measurements: The primary outcome was chart-verified completion of CRC screening within 24 weeks. Secondary outcomes were ability to state a screening preference, intention to receive screening, screening discussions, and orders for screening tests. All outcome assessors were blinded to randomization. Results: Baseline characteristics were similar between groups; 37% of participants had limited health literacy, and 53% had annual incomes less than $20 000. Screening was completed by 30% of mPATH-CRC participants and 15% of those receiving usual care (logistic regression odds ratio, 2.5 [95% CI, 1.6 to 4.0]). Compared with usual care, more mPATH-CRC participants could state a screening preference, planned to be screened within 6 months, discussed screening with their provider, and had a screening test ordered. Half of mPATH-CRC participants (53%; 118 of 223) "self-ordered" a test via the program. Limitation: Participants were English speakers in a single health care system. Conclusion: A digital health intervention that allows patients to self-order tests can increase CRC screening. Future research should identify methods for implementing similar interventions in clinical care. Primary Funding Source: National Cancer Institute.

Linking social and spatial networks to viral community phylogenetics reveals subtype-specific transmission dynamics in African lions.

Heterogeneity within pathogen species can have important consequences for how pathogens transmit across landscapes; however, discerning different transmission routes is challenging. Here, we apply both phylodynamic and phylogenetic community ecology techniques to examine the consequences of pathogen heterogeneity on transmission by assessing subtype-specific transmission pathways in a social carnivore. We use comprehensive social and spatial network data to examine transmission pathways for three subtypes of feline immunodeficiency virus (FIVPle ) in African lions (Panthera leo) at multiple scales in the Serengeti National Park, Tanzania. We used FIVPle molecular data to examine the role of social organization and lion density in shaping transmission pathways and tested to what extent vertical (i.e., father- and/or mother-offspring relationships) or horizontal (between unrelated individuals) transmission underpinned these patterns for each subtype. Using the same data, we constructed subtype-specific FIVPle co-occurrence networks and assessed what combination of social networks, spatial networks or co-infection best structured the FIVPle network. While social organization (i.e., pride) was an important component of FIVPle transmission pathways at all scales, we find that FIVPle subtypes exhibited different transmission pathways at within- and between-pride scales. A combination of social and spatial networks, coupled with consideration of subtype co-infection, was likely to be important for FIVPle transmission for the two major subtypes, but the relative contribution of each factor was strongly subtype-specific. Our study provides evidence that pathogen heterogeneity is important in understanding pathogen transmission, which could have consequences for how endemic pathogens are managed. Furthermore, we demonstrate that community phylogenetic ecology coupled with phylodynamic techniques can reveal insights into the differential evolutionary pressures acting on virus subtypes, which can manifest into landscape-level effects.

Cost Analysis of Ceramic Heads in Primary Total Hip Arthroplasty.

BACKGROUND: The advent of adverse local tissue reactions seen in metal-on-metal bearings, and the recent recognition of trunnionosis, have led many surgeons to recommend ceramic-on-polyethylene articulations for primary total hip arthroplasty. However, to our knowledge, there has been little research that has considered whether the increased cost of ceramic provides enough benefit over cobalt-chromium to justify its use. The primary purpose of this study was to compare the cost-effectiveness of ceramic-on-polyethylene implants and metal-on-polyethylene implants in patients undergoing total hip arthroplasty. METHODS: Markov decision modeling was used to determine the ceramic-on-polyethylene implant revision rate necessary to be cost-effective compared with the revision rate of metal-on-polyethylene implants across a range of patient ages and implant costs. A different set of Markov models was used to estimate the national cost burden of choosing ceramic-on-polyethylene implants over metal-on-polyethylene implants for primary total hip arthroplasties. The Premier Research Database was used to identify 20,398 patients who in 2012 were ≥45 years of age and underwent a total hip arthroplasty with either a ceramic-on-polyethylene implant or a metal-on-polyethylene implant. RESULTS: The cost-effectiveness of ceramic heads is highly dependent on the cost differential between ceramic and metal femoral heads and the age of the patient. At a cost differential of $325, ceramic-on-polyethylene bearings are cost-effective for patients <85 years of age. At a cost differential of $600, it is cost-effective to utilize ceramic-on-polyethylene bearings in patients <65 years of age, and, at a differential of $1,003, ceramic-on-polyethylene bearings are not cost-effective at any age. CONCLUSIONS: The ability to recoup the initial increased expenditure of ceramic heads through a diminished lifetime revision cost is dependent on the price premium for ceramic and the age of the patient. A wholesale switch to ceramic bearings regardless of age or cost differential may result in an economic burden to the health system. LEVEL OF EVIDENCE: Economic and decision analysis, Level III. See Instructions for Authors for a complete description of levels of evidence.

Does Increased Spending on Pharmaceutical Marketing Inhibit Pioneering Innovation?

The pharmaceutical industry has been criticized for developing and aggressively marketing drugs that do not provide significant health benefits relative to existing drugs but retain the benefits of patent protection. Critics argue that drug marketing increases health care expenditures and provides a disincentive for pioneering drug innovation. However, evidence that marketing expenditures have any relationship to new drug approvals has been anecdotal. We hypothesized that, at publicly traded pharmaceutical firms, increased marketing expenditures will result in a reduced volume of pioneering new drugs in comparison to less innovative new drugs. We also hypothesized that additional research and development spending will result in an increased volume of pioneering new drugs in comparison to less innovative drugs. Results confirm our hypotheses. Specific policy recommendations for altering firms' incentives for the development of pioneering drugs are provided.

Cost-effectiveness of quantitative pretest probability intended to reduce unnecessary medical radiation exposure in emergency department patients with chest pain and dyspnea.

OBJECTIVES: Quantitative pretest probability (qPTP) incorporated into a decision support tool with advice can reduce unnecessary diagnostic testing among patients with symptoms suggestive of acute coronary syndrome (ACS) and pulmonary embolism (PE), reducing 30-day costs without an increase in 90-day adverse outcomes. This study estimates long-term (beyond 90-day) costs and outcomes associated with qPTP. The authors hypothesized that qPTP reduces lifetime costs and improves outcomes in low-risk patients with symptoms suggestive of ACS and PE. METHODS: This was a cost-effectiveness analysis of a multicenter, randomized controlled trial of adult emergency patients with dyspnea and chest pain, in which a clinician encountering a low-risk patient with symptoms suggestive of ACS or PE conducted either the intervention (qPTP for ACS and PE with advice) or the sham (no qPTP and no advice). Effect of the intervention over a patient's lifetime was assessed using a Markov microsimulation model. Short-term costs and outcomes were from the trial; long-term outcomes and costs were from the literature. Outcomes included lifetime transition to PE, ACS, and intracranial hemorrhage (ICH); mortality from cancer, ICH, PE, ACS, renal failure, and ischemic stroke; quality-adjusted life-years (QALYs); and total medical costs compared between simulated intervention and sham groups. RESULTS: Markov microsimulation for a 40-year-old patient receiving qPTP found lifetime cost savings of $497 for women and $528 for men, associated with small gains in QALYs (2 and 6 days, respectively) and lower rates of cancer mortality in both sexes, but a reduction in ICH only in males. Sensitivity analysis for patients aged 60 years predicted that qPTP would continue to save costs and also reduce mortality from both ICH and cancer. Use of qPTP significantly reduced the lifetime probability of PE diagnosis, with lower probability of death from PE in both sexes aged 40 to 60 years. However, use of qPTP reduced the rate of ACS diagnosis and death from ACS at age 40, but increased the death rate from ACS at age 60 for both sexes. CONCLUSIONS: Widespread use of a combined qPTP for both ACS and PE has the potential to decrease costs by reducing diagnostic testing, while improving most long-term outcomes in emergency patients with chest pain and dyspnea.

Evolution of puma lentivirus in bobcats (Lynx rufus) and mountain lions (Puma concolor) in North America.

Mountain lions (Puma concolor) throughout North and South America are infected with puma lentivirus clade B (PLVB). A second, highly divergent lentiviral clade, PLVA, infects mountain lions in southern California and Florida. Bobcats (Lynx rufus) in these two geographic regions are also infected with PLVA, and to date, this is the only strain of lentivirus identified in bobcats. We sequenced full-length PLV genomes in order to characterize the molecular evolution of PLV in bobcats and mountain lions. Low sequence homology (88% average pairwise identity) and frequent recombination (1 recombination breakpoint per 3 isolates analyzed) were observed in both clades. Viral proteins have markedly different patterns of evolution; sequence homology and negative selection were highest in Gag and Pol and lowest in Vif and Env. A total of 1.7% of sites across the PLV genome evolve under positive selection, indicating that host-imposed selection pressure is an important force shaping PLV evolution. PLVA strains are highly spatially structured, reflecting the population dynamics of their primary host, the bobcat. In contrast, the phylogeography of PLVB reflects the highly mobile mountain lion, with diverse PLVB isolates cocirculating in some areas and genetically related viruses being present in populations separated by thousands of kilometers. We conclude that PLVA and PLVB are two different viral species with distinct feline hosts and evolutionary histories. Importance: An understanding of viral evolution in natural host populations is a fundamental goal of virology, molecular biology, and disease ecology. Here we provide a detailed analysis of puma lentivirus (PLV) evolution in two natural carnivore hosts, the bobcat and mountain lion. Our results illustrate that PLV evolution is a dynamic process that results from high rates of viral mutation/recombination and host-imposed selection pressure.

Impact of medication aide use on skilled nursing facility quality.

PURPOSE OF THE STUDY: A number of states have begun to allow skilled nursing facilities to employ medication aides, who have less formal education than registered nurses (RNs) or licensed practical nurses (LPNs), to administer medications. If this results in fewer RNs or LPNs, quality degradation may occur. We evaluated the effect of regulations allowing for medication aides on subsequent medication aide use and the effect of changes in medication aide use on other nurse staffing, deficiencies, and Nursing Home Quality Initiative (NHQI) health outcome measures. DESIGN AND METHODS: Staffing levels and inspection deficiencies from the Online Survey and Certification and Reporting System and NHQI data from 2004 to 2010 for facilities from eight southeastern U.S. states are used in instrumental variables models with facility fixed effects. RESULTS: Facilities in states allowing for medication aide use increased medication aide use with no statistically significant reduction in RN or LPN use. Medication aide use decreased the probability that a facility received a deficiency citation for unnecessary drug use or having a medication error rate greater than or equal to 5% and had no effect on deficiencies for significant or harmful medication errors. Increased medication aide use was associated with fewer pharmacy and total deficiency citations and decreased use of physical restraints; in contrast, more use of medication aides was associated with an increase in the percentage of residents needing help with activities of daily living and losing continence. IMPLICATIONS: This study provides support for state policies that allow skilled nursing facilities to use medication aides.

Effects of skilled nursing facility structure and process factors on medication errors during nursing home admission.

BACKGROUND: Older adults are at greatest risk of medication errors during the transition period of the first 7 days after admission and readmission to a skilled nursing facility (SNF). PURPOSE: The aim of this study was to evaluate structure- and process-related factors that contribute to medication errors and harm during transition periods at a SNF. METHODOLOGY/APPROACH: Data for medication errors and potential medication errors during the 7-day transition period for residents entering North Carolina SNFs were from the Medication Error Quality Initiative-Individual Error database from October 2006 to September 2007. The impact of SNF structure and process measures on the number of reported medication errors and harm from errors were examined using bivariate and multivariate model methods. FINDINGS: A total of 138 SNFs reported 581 transition period medication errors; 73 (12.6%) caused harm. Chain affiliation was associated with a reduction in the volume of errors during the transition period. One third of all reported transition errors occurred during the medication administration phase of the medication use process, where dose omissions were the most common type of error; however, dose omissions caused harm less often than wrong-dose errors did. Prescribing errors were much less common than administration errors but were much more likely to cause harm. PRACTICE IMPLICATIONS: Both structure and process measures of quality were related to the volume of medication errors.However, process quality measures may play a more important role in predicting harm from errors during the transition of a resident into an SNF. Medication errors during transition could be reduced by improving both prescribing processes and transcription and documentation of orders.

A cost-utility analysis comparing the cost-effectiveness of simultaneous and staged bilateral total knee arthroplasty.

BACKGROUND: The safety and efficacy of simultaneous or staged bilateral total knee arthroplasty have long been debated among orthopaedic surgeons. Advocates for simultaneous bilateral total knee arthroplasty posit that the benefits of decreased costs and recovery time, with no difference in functional outcomes, outweigh the economic costs of potential complications. The purpose of the study was to conduct a cost-utility analysis comparing simultaneous bilateral total knee arthroplasty with staged bilateral total knee arthroplasty. METHODS: A Markov model was designed to compare the cost-effectiveness of simultaneous bilateral total knee arthroplasty with that of staged bilateral total knee arthroplasty. Nationwide Inpatient Sample data sets from 2004 to 2007 were used to identify 24,574 simultaneous and 382,496 unilateral procedures. On the basis of the codes of the International Classification of Diseases, Ninth Revision, Clinical Modification, perioperative complications were categorized as minor, major, and mortality, and respective probability values were calculated. Nationwide Inpatient Sample data were used to determine hospital costs conditional on procedure type and complications. Rehabilitation costs, anesthesia costs, and heath utilities were estimated from the literature. To minimize selection bias, propensity score matching was used to match the groups on comorbid conditions, socioeconomic variables, and hospital characteristics. RESULTS: Using the matched sample, all complication rates were higher for the staged group. The estimated mean cost (in 2012 U.S. dollars) was $43,401 for simultaneous bilateral total knee arthroplasty compared with $72,233 for staged bilateral total knee arthroplasty. The quality-adjusted life years gained were 9.31 for simultaneous bilateral total knee arthroplasty and 9.29 for staged bilateral total knee arthroplasty. On the basis of these matched results, simultaneous bilateral total knee arthroplasty dominated staged bilateral total knee arthroplasty with lower costs and better outcomes. CONCLUSIONS: On the basis of this analysis, simultaneous bilateral total knee arthroplasty is more cost-effective than staged bilateral total knee arthroplasty, with lower costs and better outcomes for the average patient. These data can inform shared medical decision-making when bilateral total knee arthroplasty is indicated.

Association between traditional nursing home quality measures and two sources of nursing home complaints.

OBJECTIVE: To test for an association between traditional nursing home quality measures and two sources of resident- and caregiver-derived nursing home complaints. DATA SOURCES: Nursing home complaints to the North Carolina Long-Term Care Ombudsman Program and state certification agency from October 2002 through September 2006 were matched with Online Survey Certification and Reporting data and Minimum Data Set Quality Indicators (MDS-QIs). STUDY DESIGN: We examine the association between the number of complaints filed against a facility and measures of inspection violations, staffing levels, and MDS-QIs. DATA EXTRACTION: One observation per facility per quarter is constructed by matching quarterly data on complaints to OSCAR data from the same or most recent prior quarter and to MDS-QIs from the same quarter. One observation per inspection is obtained by matching OSCAR data to complaint totals from both the same and the immediate prior quarter. PRINCIPAL FINDINGS: There is little relationship between MDS-QIs and complaints. Ombudsman complaints and inspection violations are generally unrelated, but there is a positive relationship between state certification agency complaints and inspection violations. CONCLUSIONS: Ombudsman and state certification agency complaint data are resident- and caregiver-derived quality measures that are distinctive from and complement traditional quality measures.

The principal genetic determinants for nasopharyngeal carcinoma in China involve the HLA class I antigen recognition groove.

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy facilitated by Epstein-Barr Virus infection. Here we resolve the major genetic influences for NPC incidence using a genome-wide association study (GWAS), independent cohort replication, and high-resolution molecular HLA class I gene typing including 4,055 study participants from the Guangxi Zhuang Autonomous Region and Guangdong province of southern China. We detect and replicate strong association signals involving SNPs, HLA alleles, and amino acid (aa) variants across the major histocompatibility complex-HLA-A, HLA -B, and HLA -C class I genes (P(HLA-A-aa-site-62) = 7.4 × 10(-29); P (HLA-B-aa-site-116) = 6.5 × 10(-19); P (HLA-C-aa-site-156) = 6.8 × 10(-8) respectively). Over 250 NPC-HLA associated variants within HLA were analyzed in concert to resolve separate and largely independent HLA-A, -B, and -C gene influences. Multivariate logistical regression analysis collapsed significant associations in adjacent genes spanning 500 kb (OR2H1, GABBR1, HLA-F, and HCG9) as proxies for peptide binding motifs carried by HLA- A*11:01. A similar analysis resolved an independent association signal driven by HLA-B*13:01, B*38:02, and B*55:02 alleles together. NPC resistance alleles carrying the strongly associated amino acid variants implicate specific class I peptide recognition motifs in HLA-A and -B peptide binding groove as conferring strong genetic influence on the development of NPC in China.

The influence of home-delivered dietary approaches to stop hypertension meals on body mass index, energy intake, and percent of energy needs consumed among older adults with hypertension and/or hyperlipidemia.

BACKGROUND: It is unclear whether participation in home-delivered meal programs similar to the Older Americans Act home-delivered meals program influence weight status among older adults with hypertension and/or hyperlipidemia. OBJECTIVE: To examine the influence of a home-delivered Dietary Approaches to Stop Hypertension (DASH) meal intervention on body mass index (BMI), energy consumed, and percent of energy needs consumed. DESIGN: A 1-year randomized control trial of home-delivered DASH meals and medical nutrition therapy conducted from 2003 through 2005. Participants who received DASH meals were compared with those who did not receive meals. Data were collected in participants' homes at baseline, 6 months, and 12 months. PARTICIPANTS/SETTING: The study sample was composed of 298 adults aged >60 years with hypertension and/or hyperlipidemia residing in a county in the southeastern part of North Carolina. INTERVENTION: Participants in the meals intervention group received seven frozen meals per week for 1 year. The meals were designed to meet one third of participants' energy and nutrient needs and to comply with the DASH diet. MAIN OUTCOME MEASURES: Change in BMI, energy consumed, and percent of energy needs consumed. STATISTICAL ANALYSES PERFORMED: Difference-in-differences models were used to estimate the effects of the meal intervention on BMI, energy consumed, and percent of daily energy needs consumed. Analyses were conducted among the full sample and by subgroup (ie, race, income, and baseline obesity status). RESULTS: In the full sample, receipt of meals did not have a significant effect on BMI, energy consumed, or percent of daily energy needs consumed. Among those living at or above the 165% poverty threshold, receipt of home-delivered meals was significantly associated with a decrease in energy consumed and, therefore, percent of daily energy needs consumed. CONCLUSIONS: Participation in a home-delivered DASH meal program did not lead to weight gain or weight loss in a group of mostly overweight or obese older adults with hypertension and/or hyperlidemia.

Emerging viruses in the Felidae: shifting paradigms.

The domestic cat is afflicted with multiple viruses that serve as powerful models for human disease including cancers, SARS and HIV/AIDS. Cat viruses that cause these diseases have been studied for decades revealing detailed insight concerning transmission, virulence, origins and pathogenesis. Here we review recent genetic advances that have questioned traditional wisdom regarding the origins of virulent Feline infectious peritonitis (FIP) diseases, the pathogenic potential of Feline Immunodeficiency Virus (FIV) in wild non-domestic Felidae species, and the restriction of Feline Leukemia Virus (FeLV) mediated immune impairment to domestic cats rather than other Felidae species. The most recent interpretations indicate important new evolutionary conclusions implicating these deadly infectious agents in domestic and non-domestic felids.

Gene flow and pathogen transmission among bobcats (Lynx rufus) in a fragmented urban landscape.

Urbanization can result in the fragmentation of once contiguous natural landscapes into a patchy habitat interspersed within a growing urban matrix. Animals living in fragmented landscapes often have reduced movement among habitat patches because of avoidance of intervening human development, which potentially leads to both reduced gene flow and pathogen transmission between patches. Mammalian carnivores with large home ranges, such as bobcats (Lynx rufus), may be particularly sensitive to habitat fragmentation. We performed genetic analyses on bobcats and their directly transmitted viral pathogen, feline immunodeficiency virus (FIV), to investigate the effects of urbanization on bobcat movement. We predicted that urban development, including major freeways, would limit bobcat movement and result in genetically structured host and pathogen populations. We analysed molecular markers from 106 bobcats and 19 FIV isolates from seropositive animals in urban southern California. Our findings indicate that reduced gene flow between two primary habitat patches has resulted in genetically distinct bobcat subpopulations separated by urban development including a major highway. However, the distribution of genetic diversity among FIV isolates determined through phylogenetic analyses indicates that pathogen genotypes are less spatially structured-exhibiting a more even distribution between habitat fragments. We conclude that the types of movement and contact sufficient for disease transmission occur with enough frequency to preclude structuring among the viral population, but that the bobcat population is structured owing to low levels of effective bobcat migration resulting in gene flow. We illustrate the utility in using multiple molecular markers that differentially detect movement and gene flow between subpopulations when assessing connectivity.

Multicohort genomewide association study reveals a new signal of protection against HIV-1 acquisition.

BACKGROUND: To date, only mutations in CCR5 have been shown to confer resistance to human immunodeficiency virus type 1 (HIV-1) infection, and these explain only a small fraction of the observed variability in HIV susceptibility. METHODS: We performed a meta-analysis between 2 independent European genomewide association studies, each comparing HIV-1 seropositive cases with normal population controls known to be HIV uninfected, to identify single-nucleotide polymorphisms (SNPs) associated with the HIV-1 acquisition phenotype. SNPs exhibiting P < 10(-5) in this first stage underwent second-stage analysis in 2 independent US cohorts of European descent. RESULTS: After the first stage, a single highly significant association was revealed for the chromosome 8 rs6996198 with HIV-1 acquisition and was replicated in both second-stage cohorts. Across the 4 groups, the rs6996198-T allele was consistently associated with a significant reduced risk of HIV-1 infection, and the global meta-analysis reached genomewide significance: P(combined) = 7.76 × 10(-8). CONCLUSIONS: We provide strong evidence of association for a common variant with HIV-1 acquisition in populations of European ancestry. This protective signal against HIV-1 infection is the first identified outside the CCR5 nexus. First clues point to a potential functional role for a nearby candidate gene, CYP7B1, but this locus warrants further investigation.

Trends in potentially avoidable hospitalizations among adults in Tennessee, 1998-2006.

BACKGROUND: Potentially avoidable hospitalizations are inpatient admissions for certain conditions, called Ambulatory Care Sensitive Conditions (ACSCs), which can potentially be prevented by effective outpatient treatment of individuals who actively participate in their own care and engage in responsible personal behavior. Changes in the rates of ACSC hospitalizations over time may signal an improvement or deterioration in the quality and effectiveness of ambulatory care. These long-term trends may also suggest changes in the underlying factors such as lifestyle choices and dietary practices of individuals and families. OBJECTIVE: This study presents data from the Tennessee Hospital Discharge Datasets on changes in ACSC hospitalizations as a percent of all hospitalizations for 1998-2006. METHODS: Retrospective analysis of administrative data based on the UB-92 claims forms submitted by all short-term acute-care hospitals in Tennessee. RESULTS: Total ACSC hospitalizations in Tennessee increased by 4.2 percent between 1998 and 2006, while the total costs for ACSC hospitalizations decreased by 1.8 percent in constant 2006 dollars. In comparison, total admissions for all conditions increased by 15 percent during 1998-2006 while total hospital costs for all conditions increased by 21 percent. The rate of increase in ACSC hospitalization varied according to patient's race, insurance type, and whether the patient's health plan is managed care or fee-for-service. ACSC patients admitted through an emergency department outnumbered their counterparts who were not admitted through an emergency department by a factor of more than two throughout 1998-2006. CONCLUSIONS: Our analysis of long-term trends of ACSC hospitalizations in Tennessee reveals a mixed bag of good news and bad news. In 1998-2006, ACSC hospitalizations rose at a much lower rate than overall hospitalizations for all conditions. Meanwhile, the costs of ACSC hospitalization in 2006 constant dollars decreased while the costs of overall hospitalizations increased. Minority groups such as blacks and patients insured under TennCare did not experience much decline in ACSC hospitalizations, especially in the rates of chronic ambulatory-care sensitive conditions, when compared with their white and commercially-insured counterparts. Patients whose care was managed experienced smaller declines in ACSC hospitalizations than those not under managed care. Finally, the number of ACSC hospitalizations admitted through an ED outnumbered those admitted through the regular hospital admission department during the study period, and the gap between the two sources of admissions grew larger over time.

Role of exonic variation in chemokine receptor genes on AIDS: CCRL2 F167Y association with pneumocystis pneumonia.

Chromosome 3p21-22 harbors two clusters of chemokine receptor genes, several of which serve as major or minor coreceptors of HIV-1. Although the genetic association of CCR5 and CCR2 variants with HIV-1 pathogenesis is well known, the role of variation in other nearby chemokine receptor genes remain unresolved. We genotyped exonic single nucleotide polymorphisms (SNPs) in chemokine receptor genes: CCR3, CCRL2, and CXCR6 (at 3p21) and CCR8 and CX3CR1 (at 3p22), the majority of which were non-synonymous. The individual SNPs were tested for their effects on disease progression and outcomes in five treatment-naïve HIV-1/AIDS natural history cohorts. In addition to the known CCR5 and CCR2 associations, significant associations were identified for CCR3, CCR8, and CCRL2 on progression to AIDS. A multivariate survival analysis pointed to a previously undetected association of a non-conservative amino acid change F167Y in CCRL2 with AIDS progression: 167F is associated with accelerated progression to AIDS (RH = 1.90, P = 0.002, corrected). Further analysis indicated that CCRL2-167F was specifically associated with more rapid development of pneumocystis pneumonia (PCP) (RH = 2.84, 95% CI 1.28-6.31) among four major AIDS-defining conditions. Considering the newly defined role of CCRL2 in lung dendritic cell trafficking, this atypical chemokine receptor may affect PCP through immune regulation and inducing inflammation.

FIV diversity: FIV Ple subtype composition may influence disease outcome in African lions.

Feline immunodeficiency virus (FIV) infects domestic cats and at least 20 additional species of non-domestic felids throughout the world. Strains specific to domestic cat (FIV(Fca)) produce AIDS-like disease progression, sequelae and pathology providing an informative model for HIV infection in humans. Less is known about the immunological and pathological influence of FIV in other felid species although multiple distinct strains of FIV circulate in natural populations. As in HIV-1 and HIV-2, multiple diverse cross-species infections may have occurred. In the Serengeti National Park, Tanzania, three divergent subtypes of lion FIV (FIV(Ple)) are endemic, whereby 100% of adult lions are infected with one or more of these strains. Herein, the relative distribution of these subtypes in the population are surveyed and, combined with observed differences in lion mortality due to secondary infections based on FIV(Ple) subtypes, the data suggest that FIV(Ple) subtypes may have different patterns of pathogenicity and transmissibility among wild lion populations.

Complaints against nursing homes: comparing two sources of complaint information and predictors of complaints.

PURPOSE OF THE STUDY: Two consumer-derived measures of nursing home quality that have been underutilized by researchers are consumer complaints to the state certification agency between inspections and complaints to the Long-Term Care Ombudsman Program. This article describes these complaints, considers facility-level predictors of complaints, and examines how complaints to the 2 entities are related. DESIGN AND METHODS: This article uses North Carolina complaint data from the state certification agency and Ombudsman from 2002 to 2006. First, we outline the similarities and differences in the 2 complaint sources by considering descriptive statistics and examining the structure of the 2 agencies. Second, we examine the relationship between complaints and facility characteristics that have been predictive of traditional quality measures. Finally, we examine the relationships between the 2 types of complaints. RESULTS: We find that complaints to the 2 agencies exhibit distinct differences in substantiation rates, although the top complaint category for both agencies is quality of care. Having a higher proportion of Medicaid residents is generally not predictive of complaint volume, whereas having a higher proportion of Medicare residents is associated with higher complaint levels. IMPLICATIONS: We find a lack of association between complaints to the 2 agencies when examining specific matched categories of complaints in many cases, suggesting that the 2 entities are not duplicating efforts in these categories.