Exploring the role of effective nurse leadership during COVID-19.

The role of leadership in nursing and healthcare is continuously being examined, and has undergone increasing public and media scrutiny due to the coronavirus disease 2019 (COVID-19) pandemic. This article details a project that brought together five final-year nursing students and two experienced nurses who had all worked as part of the early response to the pandemic. Meeting regularly online, the participants sought to explore the literature on nursing leadership as well as their own clinical experience and personal reflections of leadership during the pandemic. This process, which took place over a period of four months, also enabled the participants to examine their own leadership style. Four themes emerged from the group discussions: learning about and building on the history of nursing, the participants' role in nursing leadership, effective leadership during times of uncertainty and the role of communication in effective leadership.

The role of tonic glycinergic conductance in cerebellar granule cell signalling and the effect of gain-of-function mutation.

KEY POINTS: A T258F mutation of the glycine receptor increases the receptor affinity to endogenous agonists, modifies single-channel conductance and shapes response decay kinetics. Glycine receptors of cerebellar granule cells play their functional role not continuously, but when the granule cell layer starts receiving a high amount of excitatory inputs. Despite their relative scarcity, tonically active glycine receptors of cerebellar granule cells make a significant impact on action potential generation and inter-neuronal crosstalk, and modulate synaptic plasticity in neural networks; extracellular glycine increases probability of postsynaptic response occurrence acting at NMDA receptors and decreases this probability acting at glycine receptors. Tonic conductance through glycine receptors of cerebellar granule cells is a yet undiscovered element of the biphasic mechanism that regulates processing of sensory inputs in the cerebellum. A T258F point mutation disrupts this biphasic mechanism, thus illustrating the possible role of the gain-of-function mutations of the glycine receptor in development of neural pathologies. ABSTRACT: Functional glycine receptors (GlyRs) have been repeatedly detected in cerebellar granule cells (CGCs), where they deliver exclusively tonic inhibitory signals. The functional role of this signalling, however, remains unclear. Apart from that, there is accumulating evidence of the important role of GlyRs in cerebellar structures in development of neural pathologies such as hyperekplexia, which can be triggered by GlyR gain-of-function mutations. In this research we initially tested functional properties of GlyRs, carrying the yet understudied T258F gain-of-function mutation, and found that this mutation makes significant modifications in GlyR response to endogenous agonists. Next, we clarified the role of tonic GlyR conductance in neuronal signalling generated by single CGCs and by neural networks in cell cultures and in living cerebellar tissue of C57Bl-6J mice. We found that GlyRs of CGCs deliver a significant amount of tonic inhibition not continuously, but when the cerebellar granule layer starts receiving substantial excitatory input. Under these conditions tonically active GlyRs become a part of neural signalling machinery allowing generation of action potential (AP) bursts of limited length in response to sensory-evoked signals. GlyRs of CGCs support a biphasic modulatory mechanism which enhances AP firing when excitatory input intensity is low, but suppresses it when excitatory input rises to a certain critical level. This enables one of the key functions of the CGC layer: formation of sensory representations and their translation into motor output. Finally, we have demonstrated that the T258F mutation in CGC GlyRs modifies single-cell and neural network signalling, and breaks a biphasic modulation of the AP-generating machinery.

Biphasic Modulation of NMDA Receptor Function by Metabotropic Glutamate Receptors.

A recently reported rapid potentiation of NMDA receptors by Group I metabotropic glutamate receptors (mGluRIs) via a Homer protein link is distinct from the classical, relatively slow inhibitory G-protein-associated signaling triggered by mGluRI activation. The relationship between these two mechanisms remains unknown. Here, we focused on the mGluRI-dependent modulation of NMDAR response in hippocampal dentate gyrus granule cells and cerebellar granule cells of C57BL6-J mice and found that these two contrasting mechanisms overlap competitively on the time scale from hundreds of milliseconds to seconds, with the net effect depending on the cell type. At a shorter time interval (units of millisecond), the Homer-mediated signal from mGluRIs prevails, causing upregulation of NMDAR function, in both dentate gyrus granule cells and cerebellar granule cells. Our results shed light on the possible mechanisms of anti-schizophrenia drugs that disrupt Homer-containing protein link.SIGNIFICANCE STATEMENT Here we study modulation of NMDA receptors triggered by activation of metabotropic glutamate receptors Group I via two distinct pathways: classical G-protein signaling system and newly discovered high-speed modulatory mechanism associated with Homer-protein-containing direct molecular link. We found that these two contrasting mechanisms overlap competitively on the time scale from hundreds of milliseconds to seconds, with the net effect depending on the cell type. We have also found that both crosstalk mechanisms cause significant changes in synaptic strength and plasticity. Our results resolve an apparent discrepancy between earlier studies that demonstrated contradictive effects of Homer-containing protein link disruption on NMDA receptor signaling. On top of that, our data provide a plausible explanation for unclear action mechanisms of anti-schizophrenia drugs.

Enhanced cognition and dysregulated hippocampal synaptic physiology in mice with a heterozygous deletion of PSD-95.

PSD-95 is one of the most abundant proteins of the postsynaptic density of excitatory synapses. It functions as the backbone of protein supercomplexes that mediate signalling between membrane glutamate receptors and intracellular pathways. Homozygous deletion of the Dlg4 gene encoding PSD-95 was previously found to cause a profound impairment in operant and Pavlovian conditioning in Dlg4-/- mice studied in touch screen chambers that precluded evaluation of PSD-95's role in shaping more subtle forms of learning and memory. In this study, using a battery of touch screen tests, we investigated cognitive behaviour of mice with a heterozygous Dlg4 mutation. We found that in contrast to learning deficits of Dlg4-/- mice, Dlg4+/- animals demonstrated enhanced performance in the Visual Discrimination, Visual Discrimination Reversal and Paired-Associates Learning touch screen tasks. The divergent directions of learning phenotypes observed in Dlg4-/- and Dlg4+/- mice also contrasted with qualitatively similar changes in the amplitude and plasticity of field excitatory postsynaptic potentials recorded in the CA1 area of hippocampal slices from both mutants. Our results have important repercussions for the studies of genetic models of human diseases, because they demonstrate that reliance on phenotypes observed solely in homozygous mice may obscure qualitatively different changes in heterozygous animals and potentially weaken the validity of translational comparisons with symptoms seen in heterozygous human carriers.

Arc Requires PSD95 for Assembly into Postsynaptic Complexes Involved with Neural Dysfunction and Intelligence.

Arc is an activity-regulated neuronal protein, but little is known about its interactions, assembly into multiprotein complexes, and role in human disease and cognition. We applied an integrated proteomic and genetic strategy by targeting a tandem affinity purification (TAP) tag and Venus fluorescent protein into the endogenous Arc gene in mice. This allowed biochemical and proteomic characterization of native complexes in wild-type and knockout mice. We identified many Arc-interacting proteins, of which PSD95 was the most abundant. PSD95 was essential for Arc assembly into 1.5-MDa complexes and activity-dependent recruitment to excitatory synapses. Integrating human genetic data with proteomic data showed that Arc-PSD95 complexes are enriched in schizophrenia, intellectual disability, autism, and epilepsy mutations and normal variants in intelligence. We propose that Arc-PSD95 postsynaptic complexes potentially affect human cognitive function.

Host defenses against metabolic endotoxaemia and their impact on lipopolysaccharide detection.

Bacterial endotoxin (lipopolysaccharide, LPS), is one of the most potent inducers of inflammatory signaling, yet it is abundant in the human gut and the modern diet. Small quantities of LPS routinely translocate from the gut lumen to the circulation (so-called metabolic endotoxaemia), and elevated plasma LPS concentrations are reported in a variety of chronic non-communicable diseases, including obesity, non-alcoholic fatty liver disease, atherosclerosis and type II diabetes. Murine models of experimentally-induced endotoxaemia and Toll-like receptor-4 deficiency suggest that endotoxin may promote the metabolic disturbances that underpin these diseases. However, as bioactive LPS is cleared rapidly from the circulation, and reported levels of endotoxin in human plasma vary widely, the potential relevance of metabolic endotoxaemia to human disease remains unclear. We here review insight into these questions gained from human and murine models of experimental endotoxaemia, focusing on the kinetics of LPS neutralization and its clearance from blood, the limitations of the widely used limulus assay and alternative methods for LPS quantitation. We conclude that although new methods for LPS measurement will be required to definitively quantify the extent of metabolic endotoxaemia in man, evidence from numerous approaches suggests that this molecule may play a key role in the development of diverse metabolic diseases.

Meaningful Use of Electronic Health Records and Medicare Expenditures: Evidence from a Panel Data Analysis of U.S. Health Care Markets, 2010-2013.

OBJECTIVE: To determine if recent growth in hospital and physician electronic health record (EHR) adoption and use is correlated with decreases in expenditures for elderly Medicare beneficiaries. DATA SOURCES: American Hospital Association (AHA) General Survey and Information Technology Supplement, Health Information Management Systems Society (HIMSS) Analytics survey, SK&A Information Services, and the Centers for Medicare & Medicaid Services (CMS) Chronic Conditions Data Warehouse Geographic Variation Database for 2010 through 2013. STUDY DESIGN: Fixed effects model comparing associations between hospital referral region (HRR) level measures of hospital and physician EHR penetration and annual Medicare expenditures for beneficiaries with one of four chronic conditions. Calculated hospital penetration rates as the percentage of Medicare discharges from hospitals that satisfied criteria analogous to Meaningful Use (MU) Stage 1 requirements and physician rates as the percentage of physicians using ambulatory care EHRs. PRINCIPAL FINDINGS: An increase in the hospital penetration rate was associated with a small but statistically significant decrease in total Medicare and Medicare Part A acute care expenditures per beneficiary. An increase in physician EHR penetration was also associated with a significant decrease in total Medicare and Medicare Part A acute care expenditures per beneficiary as well as a decrease in Medicare Part B expenditures per beneficiary. For the study population, we estimate approximately $3.8 billion in savings related to hospital and physician EHR adoption during 2010-2013. We also found that an increase in physician EHR penetration was associated with an increase in lab test expenses. CONCLUSIONS: Health care markets that had steeper increases in EHR penetration during 2010-2013 also had steeper decreases in total Medicare and acute care expenditures per beneficiary. Markets with greater increases in physician EHR had greater declines in Medicare Part B expenditures per beneficiary.

Physician EHR Adoption and Potentially Preventable Hospital Admissions among Medicare Beneficiaries: Panel Data Evidence, 2010-2013.

OBJECTIVE: To test for correlation between the growth in adoption of ambulatory electronic health records (EHRs) in the United States during 2010-2013 and hospital admissions and readmissions for elderly Medicare beneficiaries with at least one of four common ambulatory care-sensitive conditions (ACSCs). DATA SOURCES: SK&A Information Services Survey of Physicians, American Hospital Association General Survey and Information Technology Supplement; and the Centers for Medicare & Medicaid Services Chronic Conditions Data Warehouse Geographic Variation Database for 2010 through 2013. STUDY DESIGN: Fixed effects model estimated the relationship between hospital referral region (HRR) level measures of physician EHR adoption and ACSC admissions and readmissions. Analyzed rates of admissions and 30-day readmissions per beneficiary at the HRR level (restricting the denominator to beneficiaries in our sample), adjusted for differences across HRRs in Medicare beneficiary age, gender, and race. Calculated physician EHR adoption rates as the percentage of physicians in each HRR who report using EHR in ambulatory care settings. PRINCIPAL FINDINGS: Each percentage point increase in market-level EHR adoption by physicians is correlated with a statistically significant decline of 1.06 ACSC admissions per 10,000 beneficiaries over the study period, controlling for the overall time trend as well as market fixed effects and characteristics that changed over time. This finding implies 26,689 fewer ACSC admissions in our study population during 2010 to 2013 that were related to physician ambulatory EHR adoption. This represents 3.2 percent fewer ACSC admissions relative to the total number of such admissions in our study population in 2010. We found no evidence of a correlation between EHR use, by either physicians or hospitals, and hospital readmissions at either the market level or hospital level. CONCLUSIONS: This study extends knowledge about EHRs' relationship with quality of care and utilization. The results suggest a significant association between EHR use in ambulatory care settings and ACSC admissions that is consistent with policy goals to improve the quality of ambulatory care for patients with chronic conditions. The null findings for readmissions support the need for improved interoperability between ambulatory care EHRs and hospital EHRs to realize improvements in readmissions.

Assessing HITECH Implementation and Lessons: 5 Years Later.

POLICY POINTS: The expansive goals of the Health Information Technology for Economic and Clinical Health (HITECH) Act required the simultaneous development of a complex and interdependent infrastructure and a wide range of relationships, generating points of vulnerability. While federal legislation can be a powerful stimulus for change, its effectiveness also depends on its ability to accommodate state and local policies and private health care markets. Ambitious goals require support over a long time horizon, which can be challenging to maintain. The future of health information technology (health IT) support nationally is likely to depend on the ability of the technology to satisfy its users that its functionalities address the interests policymakers and other stakeholders have in using technology to promote better care, improved outcomes, and reduced costs. CONTEXT: The Health Information Technology for Economic and Clinical Health (HITECH) Act set ambitious goals for developing electronic health information as one tool to reform health care delivery and improve health outcomes. With HITECH's grant funding now mostly exhausted but statutory authority for standards remaining, this article looks back at HITECH's experience in the first 5 years to assess its implementation, remaining challenges, and lessons learned. METHODS: This review derives from a global assessment of the HITECH Act. Earlier, we examined the logic of HITECH and identified interdependencies critical to its ultimate success. In this article, we build on that framework to review what has and has not been accomplished in building the infrastructure authorized by HITECH since it was enacted. The review incorporates quantitative and qualitative evidence of progress from the global assessment and from the evaluations funded by the Office of the National Coordinator for Health Information Technology (ONC) of individual programs authorized by the HITECH Act. FINDINGS: Our review of the evidence provides a mixed picture. Despite HITECH's challenging demands, its complex programs were implemented, and important changes sought by the act are now in place. Electronic health records (EHRs) now exist in some form in most professional practices and hospitals eligible for HITECH incentive payments, more information is being shared electronically, and the focus of attention has shifted from adoption of EHRs toward more fundamental issues associated with using health information technology (health IT) to improve health care delivery and outcomes. In some areas, HITECH's achievements to date have fallen short of the hopes of its proponents as it has proven challenging to move meaningful use beyond the initial low bar set by Meaningful Use Stage 1. EHR products vary in their ability to support more advanced functionalities, such as patient engagement and population-based care management. Many barriers to interoperability persist, limiting electronic communication across a diverse set of largely private providers and care settings. CONCLUSIONS: Achieving the expansive goals of HITECH required the simultaneous development of a complex and interdependent infrastructure and a wide range of relationships, some better positioned to move forward than others. To date, it has proven easier to get providers to adopt EHRs, perhaps in response to financial incentives to do so, than to develop a robust infrastructure that allows the information in EHRs to be used effectively and shared not only within clinical practices but also across providers. Effective exchange of data is necessary to drive the kinds of delivery and payment reforms sought nationwide.

Geographic variation in health IT and health care outcomes: A snapshot before the meaningful use incentive program began.

BACKGROUND: The 2009 Health Information Technology for Economic and Clinical Health (HITECH) Act, which includes the Meaningful Use (MU) incentive program, was designed to increase the adoption of health information technology (IT) by physicians and hospitals. Policymakers hope that increased use of health IT to exchange health information will in turn enhance the quality and efficiency of health care delivery. In this study, we analyze the extent to which key outcomes vary based on the levels of health ITness among physicians and hospitals before the HITECH and MU programs led to increases in adoption and changes in use. Our findings provide an important baseline for a future evaluation of the impact of these programs on population-level outcomes. METHODS: We constructed measures of the degree of hospital and physician adoption and use ("health ITness") at the level of the hospital referral region (HRR). We used data from the 2010 IT Supplement of the American Hospital Association (AHA) Annual Survey of Hospitals to capture hospital health ITness and data from the 2010 survey of ambulatory health care sites produced by SK&A Information Services for the physician measure. We conducted cross-sectional analyses of the relationship between market-level Medicare costs and use and three measures: (1) physician health ITness, (2) hospital health ITness, and (3) an overall measure of health ITness. RESULTS: In general, greater levels of physician health ITness are associated with decreasing costs and use. Many of these relationships lose statistical significance, however, when we control for population and market characteristics such as the average age and health status of Medicare beneficiaries, mean household income, and the HMO penetration rate. Several of the relationships also change according to the level of hospital health ITness. CONCLUSIONS: Our findings suggest that greater levels of physician health ITness are associated with decreasing costs and use for a number of services, including inpatient costs and stays, imaging services, and lab tests, in 2010. Our health ITness and outcomes measures are aggregated at the HRR level; as such, these results do not suggest that the adoption and use of health IT by individual physicians or hospitals leads to decreases in costs or use for their individual patients. Nevertheless, these baseline findings provide important information to be considered in future research analyzing the impact of HITECH and the MU incentives.

Serum Fractalkine (CX3CL1) and Cardiovascular Outcomes and Diabetes: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

BACKGROUND: Cardiometabolic disease is a major cause of morbidity and mortality in persons with chronic kidney disease (CKD). Fractalkine (CX3CL1) is a potential mediator of both atherosclerosis and metabolic disease. Studies of the relationship of CX3CL1 with risk of cardiovascular disease (CVD) events and metabolic traits are lacking, particularly in the high-risk setting of CKD. STUDY DESIGN: Cross-sectional and longitudinal observational analysis. SETTING & PARTICIPANTS: Adults with CKD from 7 US sites participating in the Chronic Renal Insufficiency Cohort (CRIC) Study. PREDICTOR: Quartiles of plasma CX3CL1 levels at baseline. OUTCOMES: Baseline estimated glomerular filtration rate from a creatinine and cystatin C-based equation, prevalent and incident CVD, diabetes, metabolic syndrome and its criteria, homeostatic model assessment of insulin resistance, hemoglobin A1c level, myocardial infarction, all-cause mortality, and the composite outcome of myocardial infarction/all-cause mortality. RESULTS: Among 3,687 participants, baseline CX3CL1 levels were associated positively with several CVD risk factors and metabolic traits, lower estimated glomerular filtration rate, and higher levels of inflammatory cytokines, as well as prevalent CVD (OR, 1.09; 95% CI, 1.01-1.19; P=0.03). Higher CX3CL1 level also was associated with prevalent diabetes (OR, 1.26; 95% CI, 1.16-1.38; P<0.001) in adjusted models. During a mean follow-up of 6 years, there were 352 deaths, 176 myocardial infarctions, and 484 composite outcomes. In fully adjusted models, 1-SD higher CX3CL1 level increased the hazard for all-cause mortality (1.11; 95% CI, 1.00-1.22; P=0.02) and the composite outcome (1.09; 95% CI, 1.00-1.19; P=0.04). LIMITATIONS: Study design did not allow evaluation of changes over time, correlation with progression of phenotypes, or determination of causality of effect. CONCLUSIONS: Circulating CX3CL1 level may contribute to both atherosclerotic CVD and diabetes in a CKD cohort. Further studies are required to establish mechanisms through which CX3CL1 affects the pathogenesis of atherosclerosis and diabetes.

Higher plasma CXCL12 levels predict incident myocardial infarction and death in chronic kidney disease: findings from the Chronic Renal Insufficiency Cohort study.

AIMS: Genome-wide association studies revealed an association between a locus at 10q11, downstream from CXCL12, and myocardial infarction (MI). However, the relationship among plasma CXCL12, cardiovascular disease (CVD) risk factors, incident MI, and death is unknown. METHODS AND RESULTS: We analysed study-entry plasma CXCL12 levels in 3687 participants of the Chronic Renal Insufficiency Cohort (CRIC) Study, a prospective study of cardiovascular and kidney outcomes in chronic kidney disease (CKD) patients. Mean follow-up was 6 years for incident MI or death. Plasma CXCL12 levels were positively associated with several cardiovascular risk factors (age, hypertension, diabetes, hypercholesterolaemia), lower estimated glomerular filtration rate (eGFR), and higher inflammatory cytokine levels (P < 0.05). In fully adjusted models, higher study-entry CXCL12 was associated with increased odds of prevalent CVD (OR 1.23; 95% confidence interval 1.14, 1.33, P < 0.001) for one standard deviation (SD) increase in CXCL12. Similarly, one SD higher CXCL12 increased the hazard of incident MI (1.26; 1.09,1.45, P < 0.001), death (1.20; 1.09,1.33, P < 0.001), and combined MI/death (1.23; 1.13-1.34, P < 0.001) adjusting for demographic factors, known CVD risk factors, and inflammatory markers and remained significant for MI (1.19; 1.03,1.39, P = 0.01) and the combined MI/death (1.13; 1.03,1.24, P = 0.01) after further controlling for eGFR and urinary albumin:creatinine ratio. CONCLUSIONS: In CKD, higher plasma CXCL12 was associated with CVD risk factors and prevalent CVD as well as the hazard of incident MI and death. Further studies are required to establish if plasma CXCL12 reflect causal actions at the vessel wall and is a tool for genomic and therapeutic trials.

Obtaining providers' 'buy-in' and establishing effective means of information exchange will be critical to HITECH's success.

In enacting the Health Information Technology for Economic and Clinical Health (HITECH) provisions of the American Recovery and Reinvestment Act, Congress set ambitious goals for the nation to integrate information technology into health care delivery. The provisions called for the electronic exchange of health information and the adoption and meaningful use of health information technology in health care practices and hospitals. We examined the marketplace and regulatory forces that influence HITECH's success and identify outstanding challenges, some beyond the provisions' control. To reach HITECH's goals, providers and patients must be persuaded of the value of health information exchange and support its implementation. Privacy concerns and remaining technical challenges must also be overcome. Achieving HITECH's goals will require well-aligned incentives, both visionary and practical pursuit of exchange infrastructure, and realistic assumptions about how quickly such wholesale change can be accomplished. The use of metrics to show adoption proceeding at a reasonable pace, increased flow of data across parties, and evidence that care is improving, at least in areas with robust systems, will be essential to persuade stakeholders that the initiative is progressing well and warrants continued investment.

Nonfinancial barriers and access to care for U.S. adults.

OBJECTIVE: To identify prevalences and predictors of nonfinancial barriers that lead to unmet need or delayed care among U.S. adults. DATA SOURCE: 2007 Health Tracking Household Survey. STUDY DESIGN: Reasons for unmet need or delayed care in the previous 12 months were assigned to one of five dimensions in the Penchansky and Thomas model of access to care. Prevalences of barriers in each nonfinancial dimension were estimated for all adults and for adults with affordability barriers. Multivariable logistic regression models were used to estimate associations between individual, household, and insurance characteristics and barriers in each access dimension. PRINCIPAL FINDINGS: Eighteen percent of U.S. adults experienced affordability barriers and 21 percent experienced nonfinancial barriers that led to unmet need or delayed care. Two-thirds of adults with affordability barriers also reported nonfinancial barriers. Young adults, women, individuals with lower incomes, parents, and persons with at least one chronic illness had higher adjusted prevalences of nonfinancial barriers. CONCLUSIONS: Nonfinancial barriers are common reasons for unmet need or delayed care among U.S. adults and frequently coincide with affordability barriers. Failure to address nonfinancial barriers may limit the impact of policies that seek to expand access by improving the affordability of health care.

The novel atherosclerosis locus at 10q11 regulates plasma CXCL12 levels.

AIMS: Two single-nucleotide polymorphisms (SNPs), rs1746048 and rs501120, from genome wide association studies of coronary artery disease (CAD) map to chromosome 10q11 ∼80 kb downstream of chemokine CXCL12. Therefore, we examined the relationship between these two SNPs and plasma CXCL12 levels. METHODS AND RESULTS: We tested the association of two SNPs with plasma CXCL12 levels in a two-stage study (n= 2939): first in PennCath (n= 1182), a Caucasian, angiographic CAD case-control study, and second in PennCAC (n= 1757), a community-based study of CAD risk factors. Plasma CXCL12 levels increased with age and did not vary by gender. There was no linkage disequilibrium between these two SNPs and SNPs within CXCL12 gene. However, CAD risk alleles at rs1746048 (C allele, P= 0.034; CC 2.33 ± 0.49, CT 2.27 ± 0.46, and TT 2.21 ± 0.52 ng/mL) and rs501120 (T allele, P= 0.041; TT 2.34 ± 0.49, CT 2.28 ± 0.46, and CC 2.23 ± 0.53 ng/mL) were associated with higher plasma levels of CXCL12 in age and gender adjusted models. In Stage 2, we confirmed this association (rs501120, T allele, P= 0.007), and meta-analysis strengthened this finding (n= 2939, P= 6.0 × 10(-4)). Finally, in exploratory analysis, the rs1746048 risk allele tended to have higher transcript levels of CXCL12 in human natural killer cells and the liver. CONCLUSION: Coronary artery disease risk alleles downstream of CXCL12 are associated with plasma protein levels of CXCL12 and appear to be related to CXCL12 transcript levels in two human cell lines. This implicates CXCL12 as potentially causal and supports CXCL12 as a potential therapeutic target for CAD.

Treatment and outcomes for congestive heart failure by race/ethnicity in TRICARE.

BACKGROUND: Equitable access to health insurance coverage may improve outcomes of care for chronic health conditions and mitigate racial/ethnic health disparities. This study examines racial/ethnic disparities in the treatment and outcomes of care for TRICARE beneficiaries with congestive heart failure (CHF). METHODS: Using a retrospective cohort analysis, we examined demographic characteristics, sources of care, and comorbid conditions for 2183 beneficiaries of the Military Health System's TRICARE program (representing 115,584 beneficiaries after adjusting for survey weights) with CHF. Treatments included use of CHF-related medications, while the outcome of interest was any CHF-related potentially avoidable hospitalizations (PAHs). RESULTS: While African Americans were less likely than whites to have received beta blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers following a CHF diagnosis (P<0.0001). Hispanics were, in some cases, equally likely as whites to receive pharmacological treatments for CHF. In multivariate models, there were no significant racial/ethnic differences in the odds of a PAH; age greater than 65 was the most significant predictor of a PAH. CONCLUSIONS: This study suggests that although there are some racial and ethnic disparities in the receipt of pharmacological therapy for CHF among TRICARE beneficiaries, these differences do not translate into disparities in the likelihood of a PAH. The findings support previous research suggesting that equal access to care may mitigate racial/ethnic health disparities.

Clinical and functional outcomes of patients with a pathologic fracture in high-grade osteosarcoma.

BACKGROUND AND OBJECTIVES: There have been variable reports of outcomes of patients with osteosarcoma and pathologic fractures. The purpose of this study was to document outcomes after management of this clinical entity at a single large oncology center. METHODS: A retrospective review was undertaken of our database between 1989 and 2006. We compared oncologic and functional outcomes of 201 patients with high-grade osteosarcoma without pathologic fractures to 31 patients with pathologic fractures. RESULTS: The rate of amputation in the group with pathologic fracture was significantly higher than the group without fracture (39% vs. 14%, P = 0.001). There was no difference in the rate of local recurrence between groups. The 5-year survival was superior in the group without pathologic fracture (60% vs. 41%, P = 0.0015). For patients with localized disease, 5-year survival was higher in patients without fracture (68% vs. 52%, P = 0.006). Disability as measured by the Toronto Extremity Salvage Score was no different between the groups. Impairment as measured by the Musculoskeletal Tumor Society scores was lower in the group without fracture. CONCLUSIONS: Presentation with a pathologic fracture in osteosarcoma did not preclude limb salvage surgery in a majority of patients, did not increase the risk of local recurrence, but was associated with poorer overall survival.

Generic utilization and cost-sharing for prescription drugs.

PURPOSE: The purpose of this study is to estimate the own- and cross-price elasticity of brand-name outpatient prescription drug cost-sharing for maintenance medications and to estimate the effects of changes in the price differential between generic and brand-name prescription drugs. METHODOLOGY/APPROACH: We first review the literature on the effects of an increase in brand-name drug patient cost-sharing. In addition, we analyze two examples of utilization patterns in filling behavior associated with an increase in brand-name cost-sharing for patients in employer-sponsored health plans with chronic illness. FINDINGS: We found that the own-price elasticity of demand for brand-name prescription drugs was inelastic. However, the cross-price elasticity was not consistent in sign, and utilization patterns for generic prescription fills did not always increase after a rise in brand-name cost-sharing. RESEARCH LIMITATIONS: The empirical examples are limited to the experience of patients with employer-sponsored health insurance. PRACTICAL IMPLICATIONS: The common practice of increasing brand-name prescription drug patient cost-sharing to increase consumption of generic drugs may not always result in higher generic medication use. Higher brand-name drug cost-sharing levels may result in discontinuation of chronic therapies, instead of therapeutic switching. ORIGINALITY/VALUE OF CHAPTER: The value of this chapter is its singular focus on the effects of higher brand-name drug cost-sharing through a synthesis of the literature examining the own- and cross-price elasticity of demand for brand-name medications and two empirical examples of the effects of changes in brand-name cost-sharing.

Differences in prevalence, treatment, and outcomes of asthma among a diverse population of children with equal access to care: findings from a study in the military health system.

OBJECTIVE: To assess racial and ethnic differences in asthma prevalence, treatment patterns, and outcomes among a diverse population of children with equal access to health care. DESIGN: Retrospective cohort analysis. SETTING: The Military Health System. PARTICIPANTS: A total of 822 900 children aged 2 through 17 years continuously enrolled throughout 2007 in TRICARE Prime, a health maintenance organization-type benefit provided by the Department of Defense. MAIN OUTCOME MEASURES: Prevalence of diagnosed asthma, potentially avoidable asthma hospitalizations, asthma-related emergency department visits, visits to asthma specialists, and use of asthma medications among children aged 2 to 4, 5 to 10, and 11 to 17 years. RESULTS: Black and Hispanic children in all age groups were significantly more likely to have an asthma diagnosis than white children (ranging from odds ratio [OR]=1.16; 95% confidence interval [CI], 1.09-1.24; to OR=2.00; 95% CI, 1.93-2.07). Black children in all age groups and Hispanic children aged 5 to 10 years were significantly more likely to have any potentially avoidable asthma hospitalizations and asthma-related emergency department visits (ranging from OR=1.24; 95% CI, 1.11-1.37; to OR=1.99; 95% CI, 1.37-2.88) and were significantly less likely to visit a specialist (ranging from OR=0.71; 95% CI, 0.61-0.82; to OR=0.88; 95% CI, 0.79-0.98) compared with white children. Black children in all age categories were significantly more likely to have filled any prescriptions for inhaled corticosteroids compared with white children (ranging from OR=1.11; 95% CI, 1.02-1.21; to OR=1.11; 95% CI, 1.04-1.19). CONCLUSIONS: Despite universal health insurance coverage, we found evidence of racial and ethnic differences in asthma prevalence, treatment, and outcomes.