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PubMed2005

Prevalence of the metabolic syndrome in southwest Germany.

The metabolic syndrome is a highly prevalent multifaceted clinical entity. Obesity, which is part of the metabolic syndrome, is the fastest growing health-related problem worldwide. Since currently prevalence data of the metabolic syndrome are lacking from Germany, we have applied ATP III-criteria in two urban and rural cohorts. Our population-based studies provide evidence that the prevalence of the metabolic syndrome increases with age. It was found to be more prevalent in a rural population and in this group it clustered in males. As a consequence of our population-based studies evidence that especially the rural population is at high risk for future macrovascular complications is substantiated. The urgent need for preventive measures aimed at reducing the significantly increased health risk is underscored.

Adolescent↗

PubMed2005

Imaging protein molecules using FRET and FLIM microscopy.

Förster (or fluorescence) resonance energy transfer (FRET) and fluorescence lifetime imaging (FLIM) have moved center stage and are increasingly forming part of multifaceted imaging approaches. They are complementary methodologies that can be applied to advanced quantitative analyses. The widening application of FRET and FLIM has been driven by the availability of suitable fluorophores, increasingly sophisticated microscopy systems, methodologies to correct spectral bleed-through, and the ease with which FRET can be combined with other techniques. FRET and FLIM have recently found use in several applications: in the analysis of protein-protein interactions with high spatial and temporal specificity (e.g. clustering), in the study of conformational changes, in the analysis of binding sequences, and in applications such as high-throughput screening.

Fluorescence Resonance Energy Transfer↗

PubMed1987

Genetic models for linkage analysis of ataxia-telangiectasia.

Ataxia-telangiectasia (AT) is a multifaceted autosomal recessive disorder, inherited as a single gene in each family, presumably due to a defective DNA processing protein such as a recombinase, endonuclease or even a regulatory DNA-binding protein. We are attempting to identify the chromosomal location of the AT gene(s) by performing linkage analyses on a variety of genetic models. At least five AT complementation groups have been defined. This genetic heterogeneity complicates linkage analysis. Model I assumes that the complementation genes are clustered into a single genomic region and, therefore, lod scores of linkage data from all families can be added. Model II assumes that the AT complementation genes are dispersed throughout the genome and the lod scores cannot be added. This model necessitates assigning the complementation group of every family that is included in the linkage analyses and reduces the number of families in each data base. Model III utilizes heterozygote identification to follow the AT gene (in a Group A pedigree of 61 members) as a dominant trait, thereby increasing the amount of linkage information that can be derived from that family. Model IV will focus only on consanguineous offspring of first-cousin marriages, seeking to identify the location of the AT gene(s) by the increased degree of homozygosity of genetic markers in close proximity. This model has several advantages, including that much smaller numbers of patients are required. Model V assumes that a subset of our patients will carry deletions and can be used to confirm the relationship of a candidate gene to the AT phenotype. Progress: Models I and II have been used to survey 7% and 2% of the genome, respectively. (An additional 5% of the genome can be added for exclusion of the X chromosome on clinical grounds). Model III is intended to survey the entire genome. Our initial studies have surveyed approximately 30% of the genome. Several areas of increased lod scores have been identified and are under further investigation.

Ataxia Telangiectasia↗

PubMed2006

[Culturability of rat bone marrow stromal cells and evaluation for osteoblastic formation].

OBJECTIVES: We investigated culturability of bone marrow stromal cells of young mature rats and evaluated cultured cells with regard to histomorphologic features and osteoblastic formation. METHODS: Sixteen mature Wistar rats were sacrificed under high dose of ether anesthesia. Their femurs and tibias were removed, medullas and metaphyses were washed with carrier serum and the collected material was cultured in DME/F12 serum. The cells in the test medium and at the bottom of Petri dishes were studied under inverted microscope and were photographed. Then, the cells at the bottom were stained with the picro-thionin technique, examined under light microscope, and photographed. Following trypsinizing, cluster cells were dissolved and smears were prepared for histomorphologic evaluation of stromal cells. RESULTS: Rat bone marrow cells in the culture showed a high percentage of reproducibility (93.8%; 15/16). The stromal cells in Petri dishes were of different morphology, and were interspersed with large multinucleated osteoblast-like cells following staining with the picro-thionin technique. CONCLUSION: Our findings favor the opinion that cells harvested in bone marrow cell culture are very similar to osteoblastic cells and that they may stem from osteoprogenitor cells which have multifacet differentiation ability.

Animals↗

PubMed2004

The natural course of schizophrenia and psychopathological predictors of outcome. A community-based cohort study.

The natural course of schizophrenia is extremely heterogeneous and generally considered unpredictable. This prospective research investigated the natural course of schizophrenia in a community-based population linked to an Italian Mental Health Center, looking for the identification of psychopathological predictors of outcome. Forty schizophrenic patients were assessed at baseline in a stabilized phase of illness with clinical scales of psychopathology and social functioning and afterwards were followed up for 36 months. All of them were treated with antipsychotic drugs. According to their symptoms and function scores patients were empirically classified into three groups with a cluster analysis: a group characterized by low symptoms and good functioning, a group with high symptoms and poor functioning and an intermediate group. A crosstabs analysis revealed that the empirical classification correctly predicted long-term outcome. A survival analysis with comparison of distributions (Wilcoxon Gehan test) also revealed significant differences in terms of hospital admission and occurrence of alcohol-related diagnosis across groups. This study suggests that the long-term outcome in schizophrenic patients followed by a community-based mental health service is generally poor and multifaceted. However, outcome may be predicted on the basis of the psychopathological and social functioning profile assessed in a stabilized phase of illness defined with operational criteria.

Adult↗

PubMedDate not supplied

The pain of being borderline: dysphoric states specific to borderline personality disorder.

The objective of this study was to identify the dysphoric states that best characterize patients meeting criteria for borderline personality disorder and distinguish them from those in patients with other forms of personality disorder. One hundred forty-six patients with criteria-defined borderline personality disorder and 34 Axis II controls filled out the Dysphoric Affect Scale, a 50-item self-report measure that was designed for this purpose and has good internal consistency and test-retest reliability. Twenty-five dysphoric states (mostly affects) were found to be significantly more common among borderline patients than controls but nonspecific to borderline personality disorder. Twenty-five other dysphoric states (mostly cognitions) were found to be both significantly more common among borderline patients than controls and highly specific to borderline personality disorder. These states tended to fall into one of four clusters: (1) extreme feelings, (2) destructiveness or self-destructiveness, (3) fragmentation or "identitylessness," and (4) victimization. In addition, three of the 25 more-specific states (feeling betrayed, like hurting myself, and completely out of control), when occurring together, were particularly strongly associated with the borderline diagnosis. Equally important, overall mean Dysphoric Affect Scale scores correctly distinguished borderline personality disorder from other personality disorders in 84% of the subjects. Taken together, the results of this study suggest that the subjective pain of borderline patients may be both more pervasive and more multifaceted than previously recognized, and that the overall "amplitude" of this pain may be a particularly good marker for the borderline diagnosis.

Adolescent↗

PubMed2003

Increasing the efficiency of fuzzy logic-based gene expression data analysis.

DNA microarray technology can accommodate a multifaceted analysis of the expression of genes in an organism. The wealth of spatiotemporal data generated by this technology allows researchers to potentially reverse engineer a particular genetic network. "Fuzzy logic" has been proposed as a method to analyze the relationships between genes and help decipher a genetic network. This method can identify interacting genes that fit a known "fuzzy" model of gene interaction by testing all combinations of gene expression profiles. This paper introduces improvements made over previous fuzzy gene regulatory models in terms of computation time and robustness to noise. Improvement in computation time is achieved by using a cluster analysis as a preprocessing method to reduce the total number of gene combinations analyzed. This approach speeds up the algorithm by a factor of 50% with minimal effect on the results. The model's sensitivity to noise is reduced by implementing appropriate methods of "fuzzy rule aggregation" and "conjunction" that produce reliable results in the face of minor changes in model input.

Animals↗

PubMed1996

CD4+ T-lymphocyte lines developed from HIV-1-seropositive patients recognize different epitopes within the V3 loop.

To define the epitopes present within the V3 loop sequence recognized by five HIV-1 envelope-specific T-cell lines, a panel of V3 LAI peptides bearing sequential truncations from both the N- and C-terminus was synthesized and tested for their ability to induce proliferation. Each individual T-cell line had a different pattern of response against the truncated V3 peptides, demonstrating the presence of a cluster of CD4+ T-cell epitopes within the V3 loop. To assess the ability of these envelope-specific T-cell lines to recognize and proliferate in response to V3 loops of different viral strains, they were tested against a panel of heterologous V3 loop peptides derived from different viral genotypes within and outside of HIV-1 clade B. There was no proliferative response against heterologous V3 loops by any of the lines, demonstrating that recognition of the V3 epitopes is highly strain specific. One of the defined epitopes was shown to elicit a cytotoxic response as well, suggesting the multifaceted role that the CD4+ T cell might play in HIV-1 disease.

Amino Acid Sequence↗

PubMed2007

Barriers to the identification and management of psychosocial issues in children and maternal depression.

CONTEXT: Child psychosocial issues and maternal depression are underidentified and undertreated, but we know surprisingly little about the barriers to identification and treatment of these problems by primary care pediatricians. OBJECTIVES: The purpose of this work was to determine whether (1) perceived barriers to care for children's psychosocial issues and maternal depression aggregate into patient, physician, and organizational domains, (2) barrier domains are distinct for mothers and children, and (3) physician, patient, and practice/organizational characteristics are associated with different barrier domains for children and mothers. METHODS: We conducted a cross-sectional survey of the 50,818 US nonretired members of the American Academy of Pediatrics. Of a random sample of 1600 members, 832 (745 nontrainee members) responded. This was a mailed 8-page survey with no patients and no intervention. We measured physician assessment of barriers to providing psychosocial care for children's psychosocial problems and maternal depression. RESULTS: Pediatricians frequently endorse the lack of time to treat mental health problems (77.0%) and long waiting periods to see mental health providers (74.0%) as the most important barriers to the identification and treatment of children's psychosocial problems. For maternal depression, pediatricians most often endorsed lack of training in treatment (74.5%) and lack of time to treat (64.3%) as important barriers. Pediatricians' reports of barriers clustered into physician and organizational domains. Physician domains were distinct for children and mothers, but organizational domains were not. Several physician and practice characteristics are significantly associated with the 4 barrier scales, and different characteristics (eg, sociodemographic, attitudinal, and practice features) were related to each barrier area. CONCLUSIONS: Pediatricians endorse a wide range of barriers with respect to the diagnosis and treatment of children's mental health problems and maternal depression. The specificity of factors relating to various barrier areas suggests that overcoming barriers to the identification and treatment of child mental health problems and maternal depression in primary care pediatrics is likely to require a multifaceted approach that spans organizational, physician, and patient issues. In addition, comprehensive interventions will likely require social marketing approaches designed to engage diverse audiences of clinicians and their patients to participate.

Child↗

PubMed2002

Insulin resistance syndrome revisited: application of self-organizing maps.

BACKGROUND: Most common chronic diseases have a multifaceted aetiological background. Because currently used statistical methods have severe limitations in describing complex non-linear processes, the authors evaluated the usefulness of a multivariate method which is able to describe non-linear phenomena, the self-organizing map (SOM). METHODS: The study subjects were the 1650 participants of the Kuopio Ischemic Heart Disease Risk Factor Study (KIHD). The SOM model was constructed using 25 continuous biochemical and physiological variables. The aim of the SOM algorithm, together with Sammon's mapping, is to group the data into reduced but representative format and divide the study population into homogeneous subgroups. RESULTS: The study population consisted of four groups (clusters) according to the method used. In the clusters C1 to C4 were 637, 445, 275 and 121 men, respectively. There were eight neurons (n = 172) which were not included to the four main clusters. The mean values of the variables related to insulin resistance syndrome in the identified SOM map were 32.1 (kg/m(2)) for body mass index (BMI), 1.01 for waist-to-hip ratio (WHR), 158.7 mmHg and 103.8 mmHg for systolic (SBP) and diastolic blood pressure (DBP), 2.8 mmol/l for triglycerides, 6.2 mmol/l for blood glucose and 22.4 mU/l for serum insulin. There was a statistically significant difference in the mean values of BMI, WHR, SBP, DBP, HDL, triglycerides and blood glucose between the cluster representing the insulin resistance syndrome and the normal cluster. CONCLUSIONS: This study shows that the multidimensional structures of insulin resistance syndrome can be visualized and identified at qualitative and quantitative level using the SOM algorithm.

Adult↗

PubMed2006

A genome-scale assessment of peripheral blood B-cell molecular homeostasis in patients with rheumatoid arthritis.

OBJECTIVE: While rheumatoid arthritis (RA) is considered a prototypical autoimmune disease, the specific roles of B-cells in RA pathogenesis is not fully delineated. METHODS: We performed microarray expression profiling of peripheral blood B-cells from RA patients and controls. Data were analysed using differential gene expression analysis and 'gene networking' analysis (characterizing clusters of functionally inter-relelated genes) to identify both regulatory genes and the pathways in which they participate. Results were confirmed by quantitative real-time polymerase chain reaction and by measuring the levels of 10 serum cytokines involved in the pathways identified. RESULTS: Genes regulating and effecting the cell-cycle, proliferation, apoptosis, autoimmunity, cytokine networks, angiogenesis and neuro-immune regulation were differentially expressed in RA B-cells. Moreover, the serum levels of several soluble factors that modulate these pathways, including IL-1beta, IL-5, IL-6, IL-10, IL-12p40, IL-17 and VEGF were significantly increased in this cohort of RA patients. CONCLUSIONS: These results outline aspects of the multifaceted role B-cells play in RA pathogenesis in which immune dysregulation in RA modulates B-cell biology and thereby contributes to the induction and perpetuation of a pathogenic humoral immune response.

Adult↗

PubMed1986

Type A behavior: clinical significance, evaluation, and management.

Throughout recorded medical history a relationship has been postulated between the emotions and heart disease. Type A behavior is, in part, a contemporary restatement of this relationship. It is a clustering of behaviors characterized by a profound sense of time urgency, hostility, competitiveness, and a chronic struggle to obtain more and more poorly defined goals. Originally described in white urban men, it has now been shown to characterize many men and women in a variety of western industrialized societies. Type A behavior has been clearly established as a risk factor for coronary heart disease equal in magnitude to the other standard risk factors. The definitive identification of this behavior pattern is done either through a standardized interview or through one of several written tests. A simplified checklist is presented for use by the family physician in the office setting. Modification of this behavior pattern is best done using a multifaceted approach that addresses the behavioral, cognitive, physiologic, and environmental aspects. The discipline of meditation has potential as a therapeutic tool that fits in with this multifaceted approach.

Coronary Disease↗

PubMed2025

Integrating necroptosis and immune landscapes: a multi-omics-derived NecropImmScore stratifies prognosis and therapy in ovarian cancer.

BACKGROUND: Ovarian cancer (OC) remains the deadliest gynecologic malignancy, largely due to its immunosuppressive tumor microenvironment (TME) and resistance to therapy. Necroptosis, a regulated lytic cell death pathway mediated by the RIPK1-RIPK3-MLKL axis, can trigger immunogenic cell death, but its specific role in shaping the OC immune landscape and its clinical translation potential are posorly understood. METHODS: We employed multi-omics analysis (transcriptomics, genomics, clinical data) from TCGA-OV (n = 380), ICGC OV-AU, and IMvigor210 cohorts, combined with rigorous in vitro functional validation using OC cell lines (SKOV3, HEY), macrophages (THP-1 derived), and T cells (Jurkat). Computational immunology approaches (ESTIMATE, CIBERSORT, ssGSEA) quantified immune infiltration. We identified MLKL-associated immune genes, performed survival analysis (Kaplan-Meier, Cox regression), and constructed a necroptosis-immune signature (NecropImmScore) using consensus clustering and PCA of 102 prognostic genes. Drug sensitivity was predicted via pRRophetic and CellMiner. RESULTS: MLKL emerged as a protective prognostic biomarker (p = 0.018), significantly correlated with enhanced immune infiltration (ImmuneScore, StromalScore, ESTIMATEScore; p < 2.22e-16), M1 macrophage polarization (p = 0.006), activated CD4 + T cells (p = 0.003), and elevated immune checkpoint expression (PD-L1, CTLA4, LAG3, TIGIT). In vitro, MLKL overexpression in OC cells promoted M1 polarization (p < 0.05), activated Jurkat T cells (upregulated CCR4/5/7/9, CD69, CD3D/E, GZMB; p < 0.05), and induced key chemokines (CXCL9/10/11/13) critical for immune cell recruitment. Integration of MLKL-related and immune-related DEGs (n = 632) revealed enrichment in T-cell activation, chemokine signaling, and antigen presentation pathways (FDR < 0.05). Consensus clustering based on 102 survival-associated genes defined three molecular subtypes (Clusters A-C) with divergent survival (p = 0.019), necroptosis activity, and immune infiltration (Cluster C: best prognosis, highest MLKL/ImmuneScore). The derived NecropImmScore robustly stratified patients: high-score correlated with superior overall survival (TCGA: p < 0.001; ICGC: p = 0.014), inflamed TME phenotype, elevated checkpoint expression, and improved response to anti-PD-L1 in IMvigor210. Critically, high NecropImmScore predicted higher BRCA1 mutation frequency (AUC = 0.802), synergy with BRCA1 status for prognosis, higher homologous recombination deficiency (HRD) score, sensitivity to cisplatin (p = 0.014), paclitaxel (p = 0.016), gemcitabine (p = 0.017), and provided superior prognostic stratification when combined with TMB and HRD score (p < 0.001). CONCLUSION: This study establishes MLKL as a master regulator of anti-tumor immunity in OC, driving chemokine-mediated immune cell recruitment and TME reprogramming. The novel NecropImmScore is a multifaceted biomarker that effectively predicts prognosis, immunotherapy response, BRCA1 deficiency, and chemosensitivity, offering significant potential for guiding precision therapeutic strategies in OC.

Humans↗

PubMed2006

A practice-centered intervention to increase screening for domestic violence in primary care practices.

BACKGROUND: Interventions to change practice patterns among health care professionals have had mixed success. We tested the effectiveness of a practice centered intervention to increase screening for domestic violence in primary care practices. METHODS: A multifaceted intervention was conducted among primary care practice in North Carolina. All practices designated two individuals to serve as domestic violence resources persons, underwent initial training on screening for domestic violence, and participated in 3 lunch and learn sessions. Within this framework, practices selected the screening instrument, patient educational material, and content best suited for their environment. Effectiveness was evaluated using a pre/post cross-sectional telephone survey of a random selection of female patients from each practice. RESULTS: Seventeen practices were recruited and fifteen completed the study. Baseline screening for domestic violence was 16% with a range of 2% to 49%. An absolute increase in screening of 10% was achieved (range of increase 0 to 22%). After controlling for clustering by practice and other patient characteristics, female patients were 79% more likely to have been screened after the intervention (OR 1.79, 95% CI 1.43-2.23). CONCLUSION: An intervention that allowed practices to tailor certain aspects to fit their needs increased screening for domestic violence. Further studies testing this technique using other outcomes are needed.

Adult↗

PubMed2025

A multifaceted investigation into the impact of m6A methylation-related genes on pancreatic cancer, integrating insights from various databases and foundational experimental research.

BACKGROUND: Despite advances in surgical techniques, immunotherapy, the mortality rate associated with pancreatic cancer (PC) has been on the rise in recent years. Understanding the importance of RNA N6-methyladenosine (m6A) in PC is critical for prognosis, tumor microenvironment, and immunotherapy efficacy. The study aims to identify m6A methylation regulators that play an important role in the development and progression of PC by mining databases. The effect of insulin-like growth factor-binding protein 3 (IGFBP3) on pancreatic tumors was explored, and the related mechanisms were explored. METHODS: We analyzed the expression of m6A regulators in PC by digging deeper into the datasets of The Cancer Genome Atlas and Gene Expression Omnibus (GEO) databases, and analyzed its relationship with the prognosis of patients with PC, looking for m6A methylation regulators that play an important role in the development and progression of PC. Reuse the ConsensusClusterPlus package, Cox analysis, and unsupervised clustering to delineate three distinct m6A clusters - designated as m6A cluster A, m6A cluster B, and m6A cluster C single-sample gene set enrichment analysis, gene set variation analysis, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses evaluated the different pathway roles of these clusters in the development and progression of PC. Finally, the cell lines with IGFBP3 overexpression and knockdown were constructed by lentivirus transfection, the transfection effect was identified by WB, and the effects of IGFBP3 overexpression/knockdown on the survival and growth of PC cell lines were verified by cell cloning experiments and cell counting kit-8 experiments, and the possible related pathways were explored by KEGG. RESULTS: Most m6A regulatory factors are highly expressed in PC, and their high expression is negatively correlated with the prognosis of patients with PC. Furthermore, m6A regulatory factors may influence the occurrence and development of PC through metabolic pathways, stroma activation pathways, immune regulatory processes, and the immune microenvironment. Finally, the overexpression of IGFBP3 promoted the growth of PC cells, and vice versa. CONCLUSIONS: Most m6A regulatory factors are differentially expressed in PC and are associated with the prognosis of patients with PC, potentially influencing the occurrence and development of PC through pathways such as the immune microenvironment. The overexpression of IGFBP3 can promote the growth of PC cells and vice versa.

IGFBP3↗

PubMed2006

The Nef protein of human immunodeficiency virus is a broad-spectrum modulator of chemokine receptor cell surface levels that acts independently of classical motifs for receptor endocytosis and Galphai signaling.

Chemokine receptors (CKRs) are important physiological mediators of immune defense, inflammatory responses, and angiogenesis, and they have also been implicated in a number of viral disease processes. Here, we report that the Nef protein of human immunodeficiency virus (HIV) reduces cell surface levels of eight different members of the CC- and CXC-family of CKRs by up to 92%. This broad-range activity required specific elements in HIV(SF2) Nef, including the proline-rich motif P73P76P79P82 as well as the acidic cluster motif E66E67E68E69, and Nef expression induced a marked perinuclear accumulation of CKRs. Surprisingly, receptor mutagenesis demonstrated that the cytoplasmic tail of CCR5 and CXCR4, which is critical for basal and ligand-mediated endocytosis, was completely dispensable for this Nef activity. In contrast, triple-mutation of the highly conserved DRY motif in the second intracellular CKR loop abolished the Nef-mediated down-regulation of CXCR4 independently of this motif's role in CKR binding to heterotrimeric G proteins and signaling via the Galphai subunit. Thus, we identify the lentiviral pathogenicity factor Nef as a unique and broad-range modulator of CKR cell surface levels. Nef uses a mechanism that is distinct from well-established pathways orchestrating CKR metabolism and offers an interesting tool to study the multifaceted biology of CKRs.

Amino Acid Motifs↗

PubMed2026

Genome-wide identification of CXE gene family in soybean and functional characterization of GmCXE31 in lipid biosynthesis and salt tolerance.

GmCXE31 negatively regulates salt tolerance and lipid synthesis in soybean, and the cxe31-edited lines improve soybean yield and seed quality. Carboxylesterases (CXEs), as essential lipid hydrolases of the α/β-hydrolase fold superfamily, are critical for plant stress responses, hormone signaling and secondary metabolism. The key candidate gene GmCXE31 was previously identified in our laboratory through a genome‑wide association study (GWAS) of soybean lipid‑related traits. In the present study, we further identified 60 GmCXE family genes in soybean. Phylogenetic analysis clustered them into 11 conserved subfamilies. Cis-acting element analysis showed their promoters are enriched with elements related to abiotic stress, growth and hormone signaling, suggesting potential roles in soybean development and stress adaptation. GmCXE31 is highly expressed in seedling roots and responsive to strigolactones (SLs) and salt stress. Functional assays revealed that GmCXE31 negatively regulates soybean salt tolerance: its overexpression reduced salt tolerance in Arabidopsis and soybean under 150 mM NaCl stress, while its knockout enhanced this trait. Lipid profiling revealed GmCXE31-edited lines had higher seed oil content, elevated oleic/linoleic acid ratio and lower saturated fatty acid proportion, which was achieved by regulating lipid synthesis-related genes like GmNFYA. Agronomic trait analysis showed GmCXE31-edited lines had increased nodule number, plant height and single-plant yield at maturity, with opposite phenotypes in overexpression lines. In conclusion, this study elucidates the multifaceted roles of GmCXE31 in coordinating soybean salt tolerance, lipid metabolism and agronomic traits, providing theoretical and genetic resources for salt-tolerant and high-quality soybean molecular breeding.

Glycine max↗

PubMed2006

A randomized trial to assess the impact of opinion leader endorsed evidence summaries on the use of secondary prevention strategies in patients with coronary artery disease: the ESP-CAD trial protocol [NCT00175240].

BACKGROUND: Although numerous therapies have been shown to be beneficial in the prevention of myocardial infarction and/or death in patients with coronary disease, these therapies are under-used and this gap contributes to sub-optimal patient outcomes. To increase the uptake of proven efficacious therapies in patients with coronary disease, we designed a multifaceted quality improvement intervention employing patient-specific reminders delivered at the point-of-care, with one-page treatment guidelines endorsed by local opinion leaders ("Local Opinion Leader Statement"). This trial is designed to evaluate the impact of these Local Opinion Leader Statements on the practices of primary care physicians caring for patients with coronary disease. In order to isolate the effects of the messenger (the local opinion leader) from the message, we will also test an identical quality improvement intervention that is not signed by a local opinion leader ("Unsigned Evidence Statement") in this trial. METHODS: Randomized trial testing three different interventions in patients with coronary disease: (1) usual care versus (2) Local Opinion Leader Statement versus (3) Unsigned Evidence Statement. Patients diagnosed with coronary artery disease after cardiac catheterization (but without acute coronary syndromes) will be randomly allocated to one of the three interventions by cluster randomization (at the level of their primary care physician), if they are not on optimal statin therapy at baseline. The primary outcome is the proportion of patients demonstrating improvement in their statin management in the first six months post-catheterization. Secondary outcomes include examinations of the use of ACE inhibitors, anti-platelet agents, beta-blockers, non-statin lipid lowering drugs, and provision of smoking cessation advice in the first six months post-catheterization in the three treatment arms. Although randomization will be clustered at the level of the primary care physician, the design effect is anticipated to be negligible and the unit of analysis will be the patient. DISCUSSION: If either the Local Opinion Leader Statement or the Unsigned Evidence Statement improves secondary prevention in patients with coronary disease, they can be easily modified and applied in other communities and for other target conditions.

Journal Article↗