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PubMed2006

Disseminating early interventions following trauma.

Dissemination of effective early interventions following trauma is necessary to ensure the provision of the best possible care in a timely manner. To achieve this, agreement from all key stakeholders is required regarding the messages to be disseminated and the means of dissemination. This article is based on a National Institute of Mental Health sponsored symposium on the dissemination of early interventions at the 21st annual meeting of the International Society for Traumatic Stress Studies in Toronto in 2005. The current knowledge base regarding the effectiveness and dissemination of early interventions (defined here as those that are begun within the first 3 months after exposure) following trauma for children, adolescents, and adults is considered.

Adolescent↗

PubMed1994

Effect of FR128998, a novel PAF receptor antagonist, on endotoxin-induced disseminated intravascular coagulation.

This study aimed to evaluate the effect of FR128998, (1s,6s)-1-benzyl-10-(3-pyridyl-methyl)-7-thia-10-azaspiro [5,6]-dodecan-11-one 7,7-dioxide hydrochloride, a novel platelet activating factor (PAF) receptor antagonist, on endotoxin lipopolysaccharide-induced disseminated intravascular coagulation in rats. Experimental disseminated intravascular coagulation was induced by an infusion of lipopolysaccharide at 0.25 mg/kg/h for 4 h. Simultaneous infusion of FR128998 (0.25 and 1.0 mg/kg/h) with lipopolysaccharide dose dependently inhibited thrombocytopenia, but not leukopenia. The changes in coagulation parameters of disseminated intravascular coagulation, i.e., prolongation of activated partial thromboplastin time and elevated levels of fibrinogen/fibrin degradation products, were also prevented by the treatment with FR128998. In addition, FR128998 attenuated the increase in serum tumor necrosis factor (TNF) which appeared during the initial stage of disseminated intravascular coagulation. FR128998 (10 microM) also inhibited the TNF production by peripheral blood leukocytes or alveolar macrophages stimulated by lipopolysaccharide in vitro. Furthermore, TNF production induced by PAF itself in vitro was also inhibited in the presence of FR128998. These data indicate that PAF plays a pivotal role in the development of disseminated intravascular coagulation via TNF production.

Animals↗

PubMed2006

Evidence-based approaches to dissemination and diffusion of physical activity interventions.

With the increasing availability of effective, evidence-based physical activity interventions, widespread diffusion is needed. We examine conceptual foundations for research on dissemination and diffusion of physical activity interventions; describe two school-based program examples; review examples of dissemination and diffusion research on other health behaviors; and examine policies that may accelerate the diffusion process. Lack of dissemination and diffusion evaluation research and policy advocacy is one of the factors limiting the impact of evidence-based physical activity interventions on public health. There is the need to collaborate with policy experts from other fields to improve the interdisciplinary science base for dissemination and diffusion. The promise of widespread adoption of evidence-based physical activity interventions to improve public health is sufficient to justify devotion of substantial resources to the relevant research on dissemination and diffusion.

Adolescent↗

PubMed2004

Neuropsychological outcome after acute disseminated encephalomyelitis: impact of age at illness onset.

Recovery from acute disseminated encephalomyelitis in childhood appears relatively uneventful, at least when looking at functional recovery parameters such as neurologic outcome. However, neuropsychology literature suggests that relatively transient illnesses affecting the central nervous system are associated with cognitive and social sequelae, particularly when the illness occurs during the preschool years. This study investigated the impact of timing of acute disseminated encephalomyelitis on intellectual, educational, and social functioning in children. Nineteen children (10 with acute disseminated encephalomyelitis before the age of 5 years), who had been admitted to the Royal Children's Hospital, Melbourne Australia, in the past 6 years underwent a brief neuropsychologic assessment. Performance was compared with 19 control subjects, stratified for age and socioeconomic status with the acute disseminated encephalomyelitis group. Children who sustained their illness before 5 years of age were particularly vulnerable to impairments in both cognitive and social domains. In particular, a higher incidence of severe behavioral and emotional problems was reported by parents of children who had experienced acute disseminated encephalomyelitis before 5 years of age. This finding suggests that there may be long-term complications in early childhood. A multidisciplinary approach to management post-illness is warranted in this age group.

Adolescent↗

PubMed2005

Neuroimaging features of acute disseminated encephalomyelitis in childhood.

Acute and disseminated demyelination of the central nervous system in children may have many causes. This study reports a retrospective cohort of 10 consecutive pediatric cases (5 to 17 years; mean [S.D.] 12.1 [4.3] years) with a presenting diagnosis of acute disseminated encephalomyelitis and the clinical and radiologic follow-up. The evolution of magnetic resonance imaging abnormalities was determined from serial studies in nine patients with a mean (S.D.) follow-up of 334.2 (312.8) days. Resolution of magnetic resonance imaging T(2) prolongation (i.e., demyelination) within 6 months of presentation was associated most commonly with a final clinical diagnosis of acute disseminated encephalomyelitis (including the multiphasic form), but failed to meet statistical significance (Fisher's exact test; P = 0.083). Incomplete resolution of the magnetic resonance imaging signal abnormalities yielded a statistically significant association (Fisher's exact test; P = 0.048) with an abnormal neurologic outcome. In summary, we conclude that early resolution of magnetic resonance imaging signal abnormalities or recurrent demyelination within 6 months of an acute and disseminated demyelinating event suggests the diagnosis of acute disseminated encephalomyelitis in children, although this association failed to meet statistical significance. However, a statistically significant association between complete resolution of magnetic resonance imaging signal abnormalities and a normal neurologic outcome was observed.

Adolescent↗

PubMed2005

A systematic review of studies evaluating diffusion and dissemination of selected cancer control interventions.

With this review, the authors sought to determine what strategies have been evaluated (including the outcomes assessed) to disseminate cancer control interventions that promote the uptake of behavior change. Five topic areas along the cancer care continuum (smoking cessation, healthy diet, mammography, cervical cancer screening, and control of cancer pain) were selected to be representative. A systematic review was conducted of primary studies evaluating dissemination of a cancer control intervention. Thirty-one studies were identified that evaluated dissemination strategies in the 5 topic areas. No strong evidence currently exists to recommend any one dissemination strategy as effective in promoting the uptake of cancer control interventions. The authors conclude that there is a strong need for more research into dissemination of cancer control interventions. Future research should consider methodological issues such as the most appropriate study design and outcomes to be evaluated.

Diffusion of Innovation↗

PubMed1980

Antithrombin III patterns in disseminated intravascular coagulation.

Antithrombin III-heparin cofactor has now been recognized as a major inhibitor of thrombin and other serine proteases in the blood coagulation system. Since the reaction between antithrombin III and serine proteases is irreversible, one would expect antithrombin III consumption in the face of pathologic intravascular coagulation and attendant generation of thrombin, IXa, Xa, XIa, XIIa, and plasmin. Using a new assay system for antithrombin III that is unaffected by heparin or fibrino (geno) lytic degradation products, antithrombin III was monitored before and during therapy in 38 patients who had acute or chronic disseminated intravascular coagulation. It was found that early and significant decreases in anththrombin III occur in disseminated intravascular coagulation and thus may serve as a useful diagnostic tool. It was further found that monitoring antithrombin III during therapy reflected a cessation of antithrombin III consumption and, thus, served as an indicator of the efficacy of therapy in stopping the clotting process. Since the assay system is unaffected by fibrino(geno)lytic degradation products and heparin, it proved useful in monitoring the efficacy of heparin therapy for disseminated intravascular coagulation. In addition for this group of patients, it appeared that mini-heparin therapy and large doses of heparin were equally efficacious in correcting other laboratory abnormalities of disseminated intravascular coagulation, and in controlling clinical hemorrhage in disseminated intravascular coagulation.

Anticoagulants↗

PubMed1991

Heparin treatment in thrombin-induced disseminated intravascular coagulation in the baboon.

BACKGROUND AND METHODS: We postulated that low-dose heparin (10 IU/kg.hr) administered as a continuous iv infusion may prevent or ameliorate the induction of thrombin-induced disseminated intravascular coagulation in baboons under general anesthesia. In a nonrandomized experiment lasting 8 hrs, animals were divided into three groups: 11 received thrombin only (group A); ten were pretreated with heparin before thrombin administration (group B); and 15 received heparin 2 hrs after disseminated intravascular coagulation was induced with thrombin (group C). All animals were monitored hemodynamically and coagulation tests were performed hourly. Tests included the following: one-stage prothrombin ratio; activated partial thromboplastin time; fibrinogen and fibrin degradation products; thrombin time; plasma fibrinogen level; antithrombin III and activated clotting time. After the acute phase of the experiment, the animals were observed for 6 days and a postmortem examination was performed on a survivor of each group. RESULTS: Six (55%) group A animals died within 6 days, while there were no deaths in group B and one animal (7%) died in group C. In group C, the administration of heparin could not normalize the clotting profile, but the mortality rate was significantly less than in group A. The prophylactic administration of heparin in group B prevented the induction of disseminated intravascular coagulation. The postmortem findings were of interest, but no statistically valid conclusions could be made, as only one autopsy was done for each group. However, the results suggest that heparin pretreatment may protect against lung edema and liver necrosis. CONCLUSIONS: The results suggest that heparin, in a dose of 10 IU/kg.hr iv, could possibly be safely used in patients at high risk of developing disseminated intravascular coagulation and in those patients with established disseminated intravascular coagulation.

Analysis of Variance↗

PubMed1997

Effects of N omega-nitro-L-arginine methyl ester on the endotoxin-induced disseminated intravascular coagulation in porcine septic shock.

OBJECTIVES: Nitric oxide is known to prevent platelet aggregation and clot formation. Inhibitors of nitric oxide synthase might promote or enhance endotoxin disseminated intravascular coagulation. The present study was designed to evaluate the effects of the arginine analog, N omega-nitro-L-arginine methyl ester (L-NAME), on the endotoxin-induced disseminated intravascular coagulation in a porcine model of septic shock. DESIGN: Prospective, comparative, experimental study. SETTING: Laboratory at a large university hospital. SUBJECTS: Sixteen female piglets, weighing 20 to 28 kg. INTERVENTIONS: Three groups of animals were studied: a control group (n = 6); a lipopolysaccharide (LPS)-treated group (n = 5) receiving Escherichia coli endotoxin (5 micrograms/kg/min over 30 mins); and an LPS + L-NAME group (n = 5) receiving endotoxin and, 1 hr after, a bolus of L-NAME (25 mg/kg). MEASUREMENTS AND MAIN RESULTS: Hemodynamic changes, usual coagulation parameters, and plasma concentrations of thrombin-antithrombin complexes, antithrombin III activity (At III), tissue plasminogen activator, plasminogen activator inhibitor type 1, and von Willebrand factor were measured at baseline, and at 30, 60, 90, 120, 180, 240, and 300 mins. After euthanasia or death, lungs and kidneys were withdrawn for histologic study. The extent of microvascular thrombosis was assessed by a semiquantitative disseminated intravascular coagulation score. In both septic endotoxin group, administration of LPS resulted in hemodynamic changes typical of severe septic shock, with disseminated intravascular coagulation and histologic changes characterized by adult respiratory distress syndrome and kidney microthrombosis. L-NAME administration normalized mean arterial pressure with a dramatic increase in systemic vascular resistances and a marked decrease in cardiac index. The changes in usual coagulation parameters, AT III, tissue plasminogen activator, and plasminogen-activator inhibitor type 1 concentrations were not different between both septic groups. However, in the LPS + L-NAME group, thrombin-antithrombin complexes and von Willebrand factor were higher and associated with a higher histologic disseminated intravascular coagulation score. CONCLUSION: In this model of endotoxin septic shock, L-NAME administration resulted in histologic and coagulation changes consistent with an increased activation of intravascular coagulation.

Animals↗

PubMed2001

Rationale for restoration of physiological anticoagulant pathways in patients with sepsis and disseminated intravascular coagulation.

OBJECTIVE: In the pathogenesis of disseminated intravascular coagulation, dysfunctional natural anticoagulant pathways appear to play a pivotal role. In this article, we will address the mechanisms that contribute to this defect in the regulation of coagulation activation. Furthermore, we will explore the experimental and clinical evidence that restoration of these anticoagulant pathways results in clinical improvement. DATA SOURCES: We have searched and reviewed published articles on experimental studies of disseminated intravascular coagulation models in animals and clinical studies in patients with disseminated intravascular coagulation. DATA SYNTHESIS: All three major anticoagulant pathways, that is, the antithrombin pathway, the protein C system, and tissue factor pathway inhibitor, are defective in sepsis and disseminated intravascular coagulation. Several mechanisms contribute to this defect. Restoration of these pathways, in principle, by administration of coagulation inhibitor concentrates or recombinant anticoagulant factors, appears to ameliorate the coagulation disorder and, more important, result in improvement of clinically relevant outcomes, such as a reduction of organ failure and mortality. CONCLUSIONS: Restoration of disrupted physiologic anticoagulant pathways in disseminated intravascular coagulation is not only a logical point of impact in patients with sepsis and an activated coagulation system, but also is associated with an improved outcome in experimental and (initial) clinical studies.

Animals↗

PubMed2006

Toward evidence-based quality improvement. Evidence (and its limitations) of the effectiveness of guideline dissemination and implementation strategies 1966-1998.

OBJECTIVES: To determine effectiveness and costs of different guideline dissemination and implementation strategies. DATA SOURCES: MEDLINE (1966 to 1998), HEALTHSTAR (1975 to 1998), Cochrane Controlled Trial Register (4th edn 1998), EMBASE (1980 to 1998), SIGLE (1980 to 1988), and the specialized register of the Cochrane Effective Practice and Organisation of Care group. REVIEW METHODS INCLUSION CRITERIA: Randomized-controlled trials, controlled clinical trials, controlled before and after studies, and interrupted time series evaluating guideline dissemination and implementation strategies targeting medically qualified health care professionals that reported objective measures of provider behavior and/or patient outcome. Two reviewers independently abstracted data on the methodologic quality of the studies, characteristics of study setting, participants, targeted behaviors, and interventions. We derived single estimates of dichotomous process variables (e.g., proportion of patients receiving appropriate treatment) for each study comparison and reported the median and range of effect sizes observed by study group and other quality criteria. RESULTS: We included 309 comparisons derived from 235 studies. The overall quality of the studies was poor. Seventy-three percent of comparisons evaluated multifaceted interventions. Overall, the majority of comparisons (86.6%) observed improvements in care; for example, the median absolute improvement in performance across interventions ranged from 14.1% in 14 cluster-randomized comparisons of reminders, 8.1% in 4 cluster-randomized comparisons of dissemination of educational materials, 7.0% in 5 cluster-randomized comparisons of audit and feedback, and 6.0% in 13 cluster-randomized comparisons of multifaceted interventions involving educational outreach. We found no relationship between the number of components and the effects of multifaceted interventions. Only 29.4% of comparisons reported any economic data. CONCLUSIONS: Current guideline dissemination and implementation strategies can lead to improvements in care within the context of rigorous evaluative studies. However, there is an imperfect evidence base to support decisions about which guideline dissemination and implementation strategies are likely to be efficient under different circumstances. Decision makers need to use considerable judgment about how best to use the limited resources they have for quality improvement activities.

Evidence-Based Medicine↗

PubMed2026

Genomic analysis of Neisseria gonorrhoeae strains from disseminated, urogenital, and rectal infections reveals differences in genes for iron acquisition and type IV secretion.

Neisseria gonorrhoeae, an obligate human pathogen, causes the sexually transmitted infection gonorrhea. Delayed treatment or immunodeficiencies can result in a higher risk of disseminated gonococcal infection (DGI), where the infection spreads to normally sterile anatomic sites, including the bloodstream. The gonococcus produces TonB-dependent transporters (TdTs) to sequester metals from host nutritional immunity proteins. These transporters are critical for survival and are important virulence factors. We characterized genes encoding iron-regulated TdTs in the genomes of strains from disseminated (n = 47), urogenital (n = 86), and rectal (n = 12) infections. We found that gonococcal strains isolated from DGI infections were more likely to express a functional hemoglobin-iron utilization operon (hpuAB wild type and phase on [32%, n = 15/47]), to harbor nonsense mutations in tdfF (57%, n = 27/47), and were predicted to express low levels of fetA (43%, n = 20/47) when compared to strains from urogenital or rectal infections. In contrast, gonococcal strains from localized urogenital infections were associated with a higher frequency of functional tdfF genes (66%, n = 57/86) and high fetA expression (30%, n = 26/86). Additionally, strains from rectal infections were more frequently found to have high fetA expression (33%, n = 4/12) and a functional tdfF (75%, n = 9/12). Furthermore, we identified associations between the presence and absence of tdfF and the gonococcal genetic island, which encodes a type IV secretion system. These findings inform our evolving understanding of the molecular mechanisms underlying disseminated gonococcal infections.IMPORTANCEGonorrhea is an emerging, global health threat, with over 100 million new cases each year. Delayed treatment, immunosuppressive medications, and immunodeficiencies can contribute to the spread of infection to the blood, presenting as a serious disseminated manifestation. With rising antimicrobial resistance and no licensed preventative vaccine, untreatable gonorrhea is a possibility in the near future. TonB-dependent transporters are highly conserved and vital for metal acquisition and survival, making them promising targets for therapeutic or preventative strategies. Associated surface-exposed lipoproteins display greater sequence variation but contribute to metal acquisition. We analyzed the genes encoding TonB-dependent transporters and associated lipoproteins from strains associated with distinct disease manifestations. We conclude that gonococci isolated from disseminated, urogenital, and rectal sites demonstrate different phase and allelic variations in genes encoding iron transport systems and the gonococcal genetic island.

Humans↗

PubMed2005

Diffusion and dissemination of evidence-based dietary strategies for the prevention of cancer.

OBJECTIVE: The purpose was to determine what strategies have been evaluated to disseminate cancer control interventions that promote the uptake of adult healthy diet? METHODS: A systematic review was conducted. Studies were identified by searching MEDLINE, PREMEDLINE, Cancer LIT, EMBASE/Excerpta Medica, PsycINFO, CINAHL, the Cochrane Database of Systematic Reviews, and reference lists and by contacting technical experts. English-language primary studies were selected if they evaluated the dissemination of healthy diet interventions in individuals, healthcare providers, or institutions. Studies of children or adolescents only were excluded. RESULTS: One hundred one articles were retrieved for full text screening. Nine reports of seven distinct studies were included; four were randomized trials, one was a cohort design and three were descriptive studies. Six studies were rated as methodologically weak, and one was rated as moderate. Studies were not meta-analyzed because of heterogeneity, low methodological quality, and incomplete data reporting. No beneficial dissemination strategies were found except one that looks promising, the use of peer educators in the worksite, which led to a short-term increase in fruit and vegetable intake. CONCLUSIONS AND IMPLICATIONS: Overall, the quality of the evidence is not strong and is primarily descriptive rather than evaluative. No clear conclusions can be drawn from these data. Controlled studies are needed to evaluate dissemination strategies, and to compare dissemination and diffusion strategies with different messages and different target audiences.

Congresses as Topic↗

PubMed2005

Dissemination of health technology assessments: identifying the visions guiding an evolving policy innovation in Canada.

Health technology assessment (HTA) has received increasing support over the past twenty years in both North America and Europe. The justification for this field of policy-oriented research is that evidence about the efficacy, safety, and cost-effectiveness of technology should contribute to decision and policy making. However, concerns about the ability of HTA producers to increase the use of their findings by decision makers have been expressed. Although HTA practitioners have recognized that dissemination activities need to be intensified, why and how particular approaches should be adopted is still under debate. Using an institutional theory perspective, this article examines HTA as a means of implementing knowledge-based change within health care systems. It presents the results of a case study on the dissemination strategies of six Canadian HTA agencies. Chief executive officers and executives (n = 11), evaluators (n = 19), and communications staff (n = 10) from these agencies were interviewed. Our results indicate that the target audience of HTA is frequently limited to policy makers, that three conflicting visions of HTA dissemination coexist, that active dissemination strategies have only occasionally been applied, and that little attention has been paid to the management of diverging views about the value of health technology. Our discussion explores the strengths, limitations, and trade-offs associated with the three visions. Further efforts should be deployed within agencies to better articulate a shared vision and to devise dissemination strategies that are consistent with this vision.

Canada↗

PubMedDate not supplied

[The disseminated intravascular coagulation syndrome and infection].

The disseminated intravascular coagulation syndrome (1) Definition. History. (2) Etiopathogeny of the disseminated intravascular coagulation syndrome. (3) The clinical and laboratory diagnosis of the disseminated intravascular coagulation syndrome. (4) The principal infections in which the disseminated intravascular coagulation syndrome has been described: bacterial, viral, rickettsial, parasitic, mycotic. (5) Treatment of the disseminated intravascular coagulation syndrome.

Aminocaproates↗

PubMed2004

[Dissemination of research--a neglected obligation].

In contrast to research and teaching duties, the obligation to disseminate research results to the general public is poorly described and not lived up to in academic medicine. At the Norwegian University of Science and Technology's Faculty of Medicine, an interdisciplinary group met with academics to discuss and identify means for improvements. The academics reported positive attitudes to popularising and communicating their findings. Dissemination of research as a working area was, however, characterised as fragmented, incidental and too much dependent on individual enthusiasm. The most important initiatives in order to achieve better dissemination were said to be the following: more and better training in popularization and dealing with the media; development of an infrastructure for dissemination at a decentralised institutional level (defined responsibility, routines etc.); and encouragement of good presentations by making dissemination of research meritorious.

Biomedical Research↗

PubMed1993

Disseminated intravascular coagulation: pathophysiology, diagnosis, and treatment.

Disseminated intravascular coagulation is a frequent finding in critically ill patients, and may be diagnosed in the majority of patients with Gram-negative sepsis. Tissue damage may result from intravascular thrombosis, and disseminated intravascular coagulation is an underestimated causal factor in the pathogenesis of organ failure in sepsis. The diagnosis of disseminated intravascular coagulation is difficult, as the initial coagulation process that leads to thrombosis is counteracted by fibrinolytic responses, that in the context of ongoing consumption of clotting factors may result in an overwhelming bleeding tendency. Hence, depending on underlying disease, and the time at which the patient is evaluated, different laboratory results may be obtained. The treatment of disseminated intravascular coagulation is even more challenging than its diagnosis. No well-designed, controlled clinical trials exist that form a basis for rational treatment decisions. Treatment frequently needs to be individualized, and rapid adjustments may be necessitated by the course of the disease. Nonetheless, we believe that recent insights in the pathophysiology of disseminated intravascular coagulation, in particular concerning the role of the extrinsic coagulation pathway, provide ground for some optimism concerning future therapeutic options.

Anticoagulants↗

PubMed2001

Comparative analysis of tumor cell dissemination in mesenteric, central, and peripheral venous blood in patients with colorectal cancer.

BACKGROUND: Metastatic disease in colorectal cancer results from hematogenic dissemination of tumor cells. This dissemination can be explained by 2 concepts: (1) regional spread of tumor cells via portal venous drainage into the liver as the first site of metastasis and (2) early spread of tumor cells into central and peripheral venous blood as evidence of systemic hematogenic tumor cell dissemination. HYPOTHESIS: Tumor cell detection in different blood compartments could help to understand the predominant pattern of hematogenic tumor cell dissemination in colorectal cancer. DESIGN: Prospective consecutive series. SETTING: University hospital. PATIENTS AND METHODS: Mesenteric, central, and peripheral venous blood samples from 40 patients with colorectal cancer were examined by cytokeratin 20 reverse transcriptase polymerase chain reaction. MAIN OUTCOME MEASURES: Sensitivity and specificity of cytokeratin 20 reverse transcriptase polymerase chain reaction, and frequency of tumor cell detection in different blood compartments. RESULTS: Tumor cells were found in mesenteric venous blood of 20 of 40 patients, central venous blood of 6 of 40 patients, and peripheral venous blood of 2 of 19 patients. The detection rate in mesenteric venous blood was significantly higher than that in central and peripheral venous blood (P<.001). CONCLUSIONS: The significantly higher detection rate in mesenteric venous blood emphasizes the importance of the filter function of the liver for circulating tumor cells in portal venous blood. Tumor cell detection in central and peripheral venous blood, however, shows that this filtering process is limited and indicates early systemic hematogenic tumor cell dissemination in colorectal cancer.

Biomarkers, Tumor↗