Screening and Quantification of Aliphatic Primary Alkyl Corrosion Inhibitor Amines in Water Samples by Paper Spray Mass Spectrometry.

Direct analysis and identification of long chain aliphatic primary diamine Duomeen O (n-oleyl-1,3-diaminopropane), corrosion inhibitor in raw water samples taken from a large medium pressure water tube boiler plant water samples at low LODs (<0.1 pg) has been demonstrated for the first time, without any sample preparation using paper spray mass spectrometry (PS-MS). The presence of Duomeen O in water samples was confirmed via tandem mass spectrometry using collision-induced dissociation and supported by exact mass measurement and reactive paper spray experiments using an LTQ Orbitrap Exactive instrument. Data shown herein indicate that paper spray ambient ionization can be readily used as a rapid and robust method for in situ direct analysis of polymanine corrosion inhibitors in an industrial water boiler plant and other related samples in the water treatment industry. This approach was applied for the analysis of three complex water samples including feedwater, condensate water, and boiler water, all collected from large medium pressure (MP) water tube boiler plants, known to be dosed with varying amounts of polyamine and amine corrosion inhibitor components. Polyamine chemistry is widely used for example in large high pressure (HP) boilers operating in municipal waste and recycling facilities to prevent corrosion of metals. The samples used in this study are from such a facility in Coventry waste treatment facility, U.K., which has 3 × 40 tonne/hour boilers operating at 17.5 bar.

The association between neighborhood socioeconomic status and ovarian cancer tumor characteristics.

PURPOSE: Higher pathologic grade, suboptimal debulking surgery, and late-stage are markers of more aggressive and advanced ovarian cancer. Neighborhood socioeconomic status (SES) has been associated with more aggressive and advanced tumors for other cancer sites, and this may also be true for ovarian cancer. METHODS: We examined the association between neighborhood SES and ovarian cancer tumor characteristics using data on 581 women diagnosed with epithelial ovarian cancer in Cook County, Illinois. Two complementary measures (concentrated disadvantage and concentrated affluence) were used to estimate neighborhood SES. Prevalence differences and 95 % confidence intervals were estimated in logistic regression models adjusted for age and race. RESULTS: Greater disadvantage was associated with higher grade tumors (p = 0.03) and suboptimal debulking (p = 0.05) and marginally associated with later tumor stage (p = 0.20). Greater affluence was inversely associated with stage at diagnosis (p = 0.004) and suboptimal debulking (p = 0.03) and (marginally) with tumor grade (p = 0.21). CONCLUSION: Our findings suggest that lower SES, estimated by neighborhood SES, is associated with ovarian cancer tumor characteristics indicative of more advanced and aggressive disease.

Access to oral health services for urban low-income Latino children: social ecological influences.

OBJECTIVES: Using an ecological conceptual model, this study examined the social context, structural, and behavioral factors within an immigrant community that contribute to increased access and use of oral health services by Latino children. The predictors of health service use at the level of the individual, the family, the provider, and the health service system were studied for their effects on the initiation of care, continuity of care, and frequency of planned visits. METHODS: In-depth face-to-face interviews were conducted with 320 Latino mothers regarding their use of oral health services for 4-8-year-old children [Mexican (n = 221), Puerto Rican (n = 69), and Central and South American (n = 30)]. Outcome measures of dental care utilization were early age at initiation of care, continuity of care, and frequency of planned dental visits. RESULTS: Regular planned dental visits were significantly related to the structural variables of household income and provider availability. The initiation of dental care was related to the mother's beliefs about the value of early preventive dental care. Mothers were more likely to continue care if they believed that the purpose was to keep the child's teeth healthy and had satisfactory communication with the dentist. CONCLUSIONS: Identifying the structural and behavioral factors that increase the likelihood of the use of oral health services can provide the basis for developing effective interventions specific to Latino children at the neighborhood level. The study findings can be also used for designing culturally appropriate oral health promotion programs and provider coordination of care.

A head and neck lymph node classification using an anatomical grid system while maintaining clinical relevance.

PURPOSE: The current classification of head and neck lymph nodes lacks a standardized system that integrates basic anatomy and clinical relevance. Currently, anatomy texts, atlases, and journals used to educate future health care professionals use a classification system that differs from the commonly used clinical nomenclature. As a result, student trainees entering the professional world are confused by lymph node terminology. The purpose of this study was to suggest a lymph node classification system that accurately reflected anatomy and clinical applications. MATERIALS AND METHODS: A literature search was conducted on anatomic and clinical texts, atlases, journals, and Web sites. RESULTS: Two recurring classification themes were found from anatomic texts and atlases: superficial and deep chains, and local anatomic structures. Since 1988 the clinical specialties have used a Roman numeral "level" system. The differences between anatomic and clinical classification systems have led to academic frustration. After analysis, a functional classification system was developed that integrated anatomic and clinical terminology from the current classification systems. This suggested system revised the clinically accepted level system approved in 1988 and replaced the terminology with an anatomically derived naming system. CONCLUSION: This system satisfies the need for a classification that unifies anatomic and clinical applications.

A naturopathic treatment approach for mild and moderate COVID-19: A retrospective chart review.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has led to significant morbidity and mortality. Although COVID-19 vaccination is available, therapeutic options are still needed. The goal of the present manuscript is to report on a treatment strategy used in a naturopathic medical practice for mild and moderate COVID-19. DESIGN: A retrospective chart review was conducted of 30 consecutive patients diagnosed with mild and moderate COVID-19 who were provided multi-nutrient, herbal, and probiotic treatment in a rural, out-patient, naturopathic primary care setting. MAIN OUTCOMES MEASURES: The primary outcome was treatment safety; secondary outcomes included changes in symptoms, progression to severe COVID-19, incidence of long COVID, and recovery time. RESULTS: No side effects or adverse events were reported from treatment and all patients experienced resolution of symptoms presumed to be associated with COVID-19 infection. One patient who had been ill for 28 days prior to presentation was hospitalized. Five patients had an illness duration of more than one month. Time to treatment was correlated with duration of illness post-treatment (r = 0.63, p < 0.001) and more symptoms at presentation was correlated with a longer duration of illness (r = 0.52, p < 0.01). CONCLUSIONS: In this retrospective chart review, a multi-nutrient, herbal, and probiotic therapeutic approach for mild and moderate COVID-19 appeared to be well-tolerated. Delay in seeking treatment after symptom onset, as well as more symptoms at presentation, were correlated with a longer duration of illness. This treatment strategy may have clinical benefit, warranting prospective clinical trials with confirmed COVID-19 cases.

Cancer-associated fibroblasts and their influence on tumor immunity and immunotherapy.

Fibroblasts play an essential role in organogenesis and the integrity of tissue architecture and function. Growth in most solid tumors is dependent upon remodeling 'stroma', composed of cancer-associated fibroblasts (CAFs) and extracellular matrix (ECM), which plays a critical role in tumor initiation, progression, metastasis, and therapeutic resistance. Recent studies have clearly established that the potent immunosuppressive activity of stroma is a major mechanism by which stroma can promote tumor progression and confer resistance to immune-based therapies. Herein, we review recent advances in identifying the stroma-dependent mechanisms that regulate cancer-associated inflammation and antitumor immunity, in particular, the interactions between fibroblasts and immune cells. We also review the potential mechanisms by which stroma can confer resistance to immune-based therapies for solid tumors and current advancements in stroma-targeted therapies.

Cancer-associated fibroblasts: key determinants of tumor immunity and immunotherapy.

Immune-targeted approaches are rapidly changing the therapeutic landscape for cancer. In spite of that, most patients show resistance or acquire resistance to these therapies. Increasing work describing the tumor microenvironment (TME) has highlighted this space as one of the key determinants in tumor immune response and immunotherapeutic success. Frequently overlooked within this space, cancer-associated fibroblasts (CAFs) within the TME have surfaced as an important dictator of the tumor immune response. Herein, we review recent advances in defining the role of CAF-immune cell interactions in solid tumors and prospects for targeting stroma to overcome resistance to immunotherapy.

The Uneven Distribution of Medically Underserved Areas in Chicago.

Purpose: Safety net health services, such as federally funded health clinics, are interventions that aim to mitigate inequality in resource distribution, thus primarily clustered in poor areas with lack of access to health care. However, not all neighborhoods with the most needs benefit from safety net health services. In this article, we explore the distribution of a federally funded health service intervention designed to serve impoverished areas, the medically underserved areas (MUAs), and the relationship between MUA designation and neighborhood sociodemographic characteristics. Methods: We explore the spatial distribution of MUAs. The 2010 U.S. census data including 868 census tracts in Chicago were used for the analysis. We then examined the likelihood of being designated as an MUA using census tract level neighborhood demographic variables. Results: We found that the likelihood of obtaining MUA designation increases for neighborhoods with higher levels of poverty, the likelihood of being designated as an MUA begins to decline beyond the tipping point, whereas the proportion of black residents continues to increase. In census tracts that were eligible but not designated, there was a greater proportion of black residents compared with white residents (p<0.01). The census tracks also had higher mean disadvantage scores (p<0.01) and lower social capital (p<0.01). Furthermore, MUA eligible areas that were not designated as MUAs were predominantly black neighborhoods in poverty. Conclusion: Studies have documented that receiving MUA designation substantially reduces disparities in access to health care, and yet, our study finding indicates that the most racially segregated poor neighborhoods are excluded from the benefits of having such federal health safety net program. Seemingly race-neutral safety net health services may still be distributed in a way that perpetuates racial inequality in health.

Spatial access to primary care providers and colorectal cancer-specific survival in Cook County, Illinois.

BACKGROUND: Spatial access to primary care has been associated with late-stage and fatal breast cancer, but less is known about its relation to outcomes of other screening-preventable cancers such as colorectal cancer. This population-based retrospective cohort study examined whether spatial access to primary care providers associates with colorectal cancer-specific survival. METHODS: Approximately 26 600 incident colorectal cancers diagnosed between 2000 and 2008 in adults residing in Cook County, Illinois were identified through the state cancer registry and georeferenced to the census tract of residence at diagnosis. An enhanced two-step floating catchment area method measured tract-level access to primary care physicians (PCPs) in the year of diagnosis using practice locations obtained from the American Medical Association. Vital status and underlying cause of death were determined using the National Death Index. Fine-Gray proportional subdistribution hazard models analyzed the association between tract-level PCP access scores and colorectal cancer-specific survival after accounting for tract-level socioeconomic status, case demographics, tumor characteristics, and other factors. RESULTS: Increased tract-level access to PCPs was associated with a lower risk of death from colorectal cancer (hazard ratio [HR], 95% confidence interval [CI]) = 0.87 [0.79, 0.96], P = .008, highest vs lowest quintile), especially among persons diagnosed with regional-stage tumors (HR, 95% CI = 0.80 [0.69, 0.93], P = .004, highest vs lowest quintile). CONCLUSIONS: Spatial access to primary care providers is a predictor of colorectal cancer-specific survival in Cook County, Illinois. Future research is needed to determine which areas within the cancer care continuum are most affected by spatial accessibility to primary care such as referral for screening, accessibility of screening and diagnostic testing, referral for treatment, and access to appropriate survivorship-related care.

Modified visual analog scale symptom-intensity and overall-bother measures for the assessment of symptoms in studies of pharmacologic stress agents.

BACKGROUND: Drugs used to induce stress for cardiac imaging studies often cause discomfort. Patient-reported intensity of discomfort should be considered when comparing such agents. OBJECTIVE: The purpose of this study was to assess the psychometric properties of a modified visual analog scale (VAS) symptom-intensity measure and an overall-bother measure adapted to assess patient-reported intensity of the adverse events (AEs) associated with pharmacologic stress testing with adenosine, a pharmacologic stress myocardial perfusion imaging (PS-MPI) agent. METHODS: Data were based on 2 complementary, open-label, multicenter, naturalistic, observational studies among patients completing a PS-MPI procedure. Content, concurrent, and discriminant validity was examined by correlating modified VAS symptom-intensity scores obtained from patients with investigator-rated intensity at time of event, overall bother, and patient-reported measures obtained during a structured interview. Test-retest reliability of the overall-bother measure was examined using 1- and 2-hour assessments, and concurrent validity was assessed by correlating counts of symptoms and other patient-reported measures. Responsiveness was examined by calculating change scores of the VAS symptom-intensity measures from baseline to 1 hour among patients who reported symptoms during the 1-hour monitoring period after PS infusion. Low to moderate correlation was defined as a coefficient between 0.3 and 0.5. RESULTS: A total of 324 patients enrolled in the 2 studies. Content validity of the VAS symptom-intensity and overall-bother measures was established, with nearly all patients reporting that they were a useful way to rate symptom intensity and overall bother. VAS ratings were moderately to highly correlated with physician-rated AE intensity, and patient-reported assessments of symptom intensity, discomfort, and concern (r(s) = 0.21 r(s) = 0.84). Findings to support discriminant validity were inconclusive because of small sample size. Responsiveness was demonstrated with VAS symptom-intensity change scores ranging from 2.8 for headache to 4.9 for chest pain; effect sizes for these differences were large, ranging from 1.6 to 7.3, respectively. CONCLUSION: Findings support the validity, reliability, and responsiveness of the modified VAS symptom-intensity measure, and the reliability and validity of the overall-bother measure for use in patients completing PS procedures.

Economic, racial and ethnic disparities in breast cancer in the US: towards a more comprehensive model.

Using cancer registry data, we focus on racial and ethnic disparities in stage of breast cancer diagnosis in Cook County, IL. The county health system is the "last resort" health-care provider for low-income persons. Socioeconomic status is measured using empirical Bayes estimates of tract-level poverty, specific to non-Hispanic whites, non-Hispanic blacks or Hispanics in one of three age groups. We use ordinal logistic regression with non-proportional odds to model stage. Blacks and Hispanics are at greater risk for regional and distant stage diagnosis, but the disparity declines with age. Women in high-poverty areas are at substantially greater risk for late-stage diagnosis. The effects of poverty do not differ by age or across racial and ethnic groups.

Multilevel Examination of Health Disparity: The Role of Policy Implementation in Neighborhood Context, in Patient Resources, and in Healthcare Facilities on Later Stage of Breast Cancer Diagnosis.

BACKGROUND: There is a substantial racial/ethnic disparity in female breast cancer mortality in Chicago between non-Hispanic black (NHblack) and Hispanic patients compared with their non-Hispanic white (NHwhite) counterparts. This observation prompted a multilevel examination of factors that might account for the disparity, with the goal of identifying potential policy interventions that might meaningfully address it METHODS: In the Breast Cancer Care in Chicago study, 411 NHblack, 397 NHwhite, and 181 Hispanic patients diagnosed between the ages of 30 and 79 were interviewed, and medical records were abstracted for information on screening and diagnostic follow-up. We conducted a multilevel analysis to assess the role of neighborhood context, patient resources, facility characteristics, and mode of detection in determining the disparity in later stage at diagnosis. RESULTS: After adjustment for neighborhood context, mode of detection, and facility accreditation/resources, there was no significant disparity in later stage breast cancer diagnosis between NHblack or Hispanic patients compared with NHwhite patients. CONCLUSIONS: The results suggest that racial/ethnic differences in mode of detection and facility accreditation/resources account for most of the disparity in stage at diagnosis. Understanding the causes of differential screen detection and access to highly accredited facilities could inform interventions to meaningfully address this disparity. IMPACT: Multilevel approaches to studying health disparities are becoming the research standard for understanding and addressing health disparities. Optimal design of multilevel interventions addressing disparities in later stage diagnosis would benefit from enhanced understanding of pathways to detection and diagnosis available to patients in medically underserved communities.

Deletion of Calcineurin Promotes a Protumorigenic Fibroblast Phenotype.

Fibroblast activation is a crucial step in tumor growth and metastatic progression. Activated fibroblasts remodel the extracellular matrix (ECM) in primary tumor and metastatic microenvironments, exerting both pro- and antitumorigenic effects. However, the intrinsic mechanisms that regulate the activation of fibroblasts are not well-defined. The signaling axis comprising the calcium-activated Ser/Thr phosphatase calcineurin (CN), and its downstream target nuclear factor of activated T cells, has been implicated in endothelial (EC) and immune cell activation, but its role in fibroblasts is not known. Here, we demonstrate that deletion of CN in fibroblasts in vitro altered fibroblast morphology and function consistent with an activated phenotype relative to wild-type fibroblasts. CN-null fibroblasts had a greater migratory capacity, increased collagen secretion and remodeling, and promoted more robust EC activation in vitro. ECM generated by CN-null fibroblasts contained more collagen with greater alignment of fibrillar collagen compared with wild-type fibroblast-derived matrix. These differences in matrix composition and organization imposed distinct changes in morphology and cytoskeletal architecture of both fibroblasts and tumor cells. Consistent with this in vitro phenotype, mice with stromal CN deletion had a greater incidence and larger lung metastases. Our data suggest that CN signaling contributes to the maintenance of fibroblast homeostasis and that loss of CN is sufficient to promote fibroblast activation. SIGNIFICANCE: Calcineurin signaling is a key pathway underlying fibroblast homeostasis that could be targeted to potentially prevent fibroblast activation in distant metastatic sites.

Neighborhood change and distant metastasis at diagnosis of breast cancer.

PURPOSE: To test whether upward socioeconomic neighborhood change has an effect on probability of distant metastasis at diagnosis of breast cancer among women who live there. METHODS: Census tract data (N = 1,137) from Cook County. IL, from 1990 and 2000 and cancer registry data for female breast cancer cases for these census tracts from 1994-2000 (N = 21,516) were used. A multilevel model of 1990 baseline socioeconomic status (SES) of neighborhoods and degree of neighborhood change 1990-2000 (compositional characteristics) and patient's age and race/Hispanic status (individual characteristics) was constructed to predict distant metastasis (vs. local and regional stage) at diagnosis. RESULTS: While residence in a census tract with lower baseline SES in 1990 (higher concentrated disadvantage and immigration and lower concentrated affluence) and being African American were associated with increased odds of distant metastasis at diagnosis, residence in an improving census tract was also associated with increased odds of distant metastasis at diagnosis. CONCLUSIONS: Paradoxically, both measures of initial neighborhood disadvantage and upward neighborhood socioeconomic change were independently associated with greater odds of distant metastasis at diagnosis of breast cancer. Neighborhood social and economic change can affect health.

Design, rationale, and populations of an international outcomes and utilization study of pharmacologic stress SPECT myocardial perfusion imaging in contemporary practice.

BACKGROUND: A prospective, international, multicenter, observational study was conducted to investigate patient and population characteristics; utilization of radiopharmaceuticals and pharmacologic stress (PS) agents; imaging protocols; clinical outcomes; the incidence, intensity, and time to onset of adverse events; and the prognostic value of single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) procedures. The rationale, study methods, and data on presenting populations are described. METHODS AND RESULTS: Investigators recorded the demographics, American College of Cardiology/American Heart Association pretest likelihood for coronary artery disease, cardiovascular risk factors, antianginal drug use, use of PS agents and associated adverse events, and radiopharmaceutical(s) and imaging protocol for each patient enrolled. SPECT images were reconstructed at each site; investigators assigned summed stress and summed rest scores using a 17-segment model (rating perfusion on a scale ranging from 0 to 4). Patients were followed up for 1 year for clinical outcomes of revascularization, nonfatal myocardial infarction, or death. CONCLUSION: The design offers a unique opportunity to study the characteristics of patients referred for SPECT imaging over a period of time consistent with the laboratories' usual practices, provides an up-to-date PS safety registry, and allows assessment of the prognostic value of PS SPECT MPI across a wide number of covariables, as well as relationships between patient and population characteristics, SPECT MPI results, and clinical outcomes.

Adrenergic hormones induce extrapituitary prolactin gene expression in leukocytes-potential implications in obesity.

The pituitary hormone prolactin (PRL), originally described for its role in lactation, has been implemented in over 300 functions and is produced by multiple cell types outside of the pituitary. Monocyte/macrophages in particular show robust expression of extra-pituitary prolactin (ePRL). While ePRL protein is identical to pituitary PRL and translated from the same gene, tissues outside the pituitary engage an alternative promoter to regulate expression. Many of the factors regulating this expression, however, remain unknown. Here we show that the adrenergic hormones epinephrine and norepinephrine induce PRL expression in the human monocytic cell line THP-1 at physiological concentrations. Furthermore, our experiments show the polarization state of differentiated macrophages can influence their response in vitro, with inflammatory M1 macrophages-common in obese adipose-showing the highest levels of PRL expression compared to other macrophage types. Adrenergic hormones have a clearly defined role in adipocyte lipid metabolism, stimulating lipolysis through hormone sensitive lipase (HSL) induction. Meanwhile, PRL has been shown to stimulate lipogenesis. This highlights ePRL production as a possible factor in obesity. The overall balance of these two signals could play a critical role in determining overall lipid turnover/accumulation in adipose depots where large numbers of adipose tissue macrophages (ATMs) reside.

Coronary circulation responses to binodenoson, a selective adenosine A2A receptor agonist.

The purpose of this study was to define binodenoson dosing regimens that produce coronary hyperemia comparable to those of adenosine and that are tolerated well by patients. An open-label, randomized, parallel-group, multicenter study enrolled adult patients who had completed diagnostic cardiac catheterization. Coronary blood flow velocity (CBFV) was measured with a Doppler flow wire, and CBFV reserve was determined before binodenoson administration. Patients (n = 133) received a 3-minute infusion of 0.3, 0.5, or 1 microg/kg/min or a bolus intravenous injection of 1.5 or 3 microg/kg. Coronary hyperemic responses were evident within seconds of administering binodenoson, and the magnitudes and durations of coronary hyperemic responses were dose related. The 1.5- and 3-microg/kg doses, by infusion or bolus, produced maximal coronary hyperemia equivalent to CBFV reserve. All doses transiently decrease blood pressure and increased heart rate and rate-pressure product. In conclusion, the 1.5-microg/kg binodenoson bolus dose produced nearly maximal coronary hyperemia by 4.5 +/- 3.7 minutes that was sustained for 7.4 +/- 6.86 minutes, was accompanied by modest changes in blood pressure, heart rate, and rate-pressure product, and produced no adverse changes on electrocardiogram, including no second- or third-degree atrioventricular block.

Implications for education in complementary and alternative medicine: a survey of entry attitudes in students at five health professional schools.

INTRODUCTION: The National Institutes of Health provided grants to the Oregon Health & Science University (OHSU) and 14 other allopathic academic health centers for the development of curricula in complementary and alternative medicine (CAM). A key component of the curriculum evaluation for OHSU was provided by a survey assessing attitudes toward CAM and selected personality characteristics of entering students in chiropractic, naturopathic, Oriental, and allopathic medicine in the Pacific Northwest and Upper Midwest. METHODS: A survey containing a variety of assessments of attitudes toward CAM and the personality traits of adventurousness and tolerance to ambiguity was administered to students entering four Portland, Oregon doctoral-level health professional schools and an allopathic medical school in the Upper Midwest (University of Nebraska College of Medicine) during the 2004-2005 academic year. RESULTS: Students of naturopathy (n = 63) and Oriental Medicine (n = 71) were the most "CAM positive," adventurous and tolerant of ambiguity, and Midwestern allopathic medical students (n = 58) the least. In general, chiropractic students (n = 89) and allopathic medical students from the Pacific Northwest (n = 95) were intermediate in CAM attitudes between these two groups (all p < 0.05). Female students were more "CAM positive" in all schools compared to male students. CONCLUSIONS: Students have high levels of interest in CAM upon entrance to their schools. Health professional discipline, geographic location, personality qualities, and gender appear to influence CAM attitudes in entering students.

Response to a proposal for an integrative medicine curriculum.

BACKGROUND: A paper entitled "Core Competencies in Integrative Medicine for Medical School Curricula: A proposal," published in Academic Medicine, stimulated a broad discussion among complementary and alternative medicine (CAM) educators. This discussion led to a formal process for responding to the issues raised by the paper. METHODS: Representatives from the Academic Consortium for Complementary and Alternative Health Care (ACCAHC) and the Oregon Collaborative for Complementary and Integrative Medicine (OCCIM) formed the ACCAHC/OCCIM Task Force to participate in a Delphi process of consultation and deliberation. This process led to a broad, cross-discipline agreement on important points to include in a response to the integrative medicine (IM) curriculum proposal. RESULTS: Five key areas of concern emerged: (1) the definition of IM as presented in the paper; (2) lack of clarity about the goals of the proposed IM curriculum; (3) lack of recognition of the breadth of whole systems of health care; (4) omission of competencies related to collaboration between MDs and CAM professionals in patient care; and (5) omission of potential areas of partnership in IM education. CONCLUSIONS: A major overall theme emerging from the Delphi process was a desire for closer collaboration between conventional medical schools and CAM academic institutions in developing IM curricula. Several cross-disciplinary venues for addressing the Delphi Task Force themes include the National Center for Complementary and Alternative Medicine's R-25 Initiatives, and the National Education Dialogue. OCCIM is presented as an example of a successful lateral integration approach.

Randomized, controlled dose-ranging study of the selective adenosine A2A receptor agonist binodenoson for pharmacological stress as an adjunct to myocardial perfusion imaging.

BACKGROUND: Dipyridamole and adenosine cause frequent side effects as a result of nonspecific adenosine receptor stimulation. Selective agonism of the adenosine A2A receptor should result in a similar degree of coronary vasodilation (and thus similar perfusion images) with fewer side effects. METHODS AND RESULTS: In a multicenter, randomized, single-blind, 2-arm crossover trial, 240 patients underwent 2 single photon emission computed tomographic (SPECT) imaging studies in random order, first after pharmacological stress with adenosine and a second study with the selective adenosine A2A receptor agonist binodenoson, using 1 of 4 dosing regimens. Safety, tolerability, and SPECT image concordance between the 2 agents were examined. Exact categorical agreement in the extent and severity of reversible perfusion defects ranged from 79% to 87%, with kappa values from 0.69 to 0.85, indicating very good to excellent agreement between binodenoson and adenosine. The risk of any safety event/side effect was significantly lower with any dose of binodenoson than with adenosine (P< or =0.01) because of a dose-related reduction in subjective side effects, as objective events were infrequent. There was a reduction in the severity of chest pain, dyspnea, and flushing in all binodenoson doses compared with adenosine (P<0.01), and the magnitude of severity reduction was dose-related. CONCLUSIONS: The selective adenosine A2A receptor agonist binodenoson results in an extent and severity of reversible perfusion defects on SPECT imaging similar to nonselective adenosine receptor stimulation, accompanied by a dose-related reduction in the incidence and severity of side effects.