From recommendation to action: psychosocial factors influencing physician intention to use Health Technology Assessment (HTA) recommendations

Background

The Evidence-Based Practice (EBP) Project has been investigating the implementation of evidence-based mental health practices (Assertive Community Treatment, Family Psychoeducation, Integrated Dual Diagnosis Treatment, Illness Management and Recovery, and Supported Employment) in state public mental health systems in the United States since 2001. To date, Project findings have yielded valuable insights into implementation strategy characteristics and effectiveness. This paper reports results of an effort to identify and classify state-level implementation activities and strategies employed across the eight states participating in the Project.

Methods

Content analysis and Greenhalgh et al's (2004) definition of innovation were used to identify and classify state-level activities employed during three phases of EBP implementation: Pre-Implementation, Initial Implementation and Sustainability Planning. Activities were coded from site visit reports created from documents and notes from key informant interviews conducted during two periods, Fall 2002 – Spring 2003, and Spring 2004. Frequency counts and rank-order analyses were used to examine patterns of implementation activities and strategies employed across the three phases of implementation.

Results

One hundred and six discreet implementation activities and strategies were identified as innovative and were classified into five categories: 1) state infrastructure building and commitment, 2) stakeholder relationship building and communications, 3) financing, 4) continuous quality management, and 5) service delivery practices and training. Implementation activities from different categories were employed at different phases of implementation.

Conclusion

Insights into effective strategies for implementing EBPs in mental health and other health sectors require qualitative and quantitative research that seeks to: a) empirically test the effects of tools and methods used to implement EBPs, and b) establish a stronger evidence-base from which to plan, implement and sustain such efforts. This paper offers a classification scheme and list of innovative implementation activities and strategies. The classification scheme offers potential value for future studies that seek to assess the effects of various implementation processes, and helps establish widely accepted standards and criteria that can be used to assess the value of innovative activities and strategies.     

Regional difference in endothelium-dependent vascular responses upon the flow rate elevation

In anaesthetised rabbits, femoral artery manifested a maximal reserve capacity in its vasodilatory response to the flow speed acceleration. In order of the capacity diminishing, this artery is followed by renal artery, abdominal aorta, celiacus tube, common carotid artery. The endothelium-dependent flow-induced response is important for restricting the flow's linear speed.     

Use of genetically modified embryonic stem cells for creating transgenic animals

Targeted genetic modification of embryonic stem cells (ESC) was used to obtain nondifferentiated cell clones containing the foreign genetic material in the genome. It was demonstrated that transgenic animals may be obtained by ESC injection in preimplantation embryos and subsequent transplantation of the embryos into a recipient female. Using this method, we constructed chimeric animals with a modified genome.     

Does sucrose influence the properties of DMPC vesicles?

Small-angle neutron and X-ray scattering, dynamic light scattering, X-ray diffraction coupled with differential scanning calorimetry, and Raman spectroscopy were applied to investigate unilamellar (ULVs) and multilamellar (MLVs) dimyristoylphosphatidylcholine (DMPC) vesicles in aqueous sucrose solutions with sucrose concentrations from 0 to 60% w/w. In case of ULVs, the addition of sucrose decreases the polydispersity of vesicle population. A minimum value of polydispersity was found at 20% sucrose. For sucrose concentration from 0 to 35% oligolamellar vesicles in the ULV population have a minimum presence. Vesicles with 5-10% sucrose exhibit the best stability in time. For the case of MLVs, sucrose influences the temperature of the phase transitions, but the internal membrane structure remains unchanged.     

Variants of adenovirus type 5 with deletions in early genes: ability for selective replication in p53-defective human tumor cells

Site-directed mutagenesis was used to construct human adenovirus serotype 5 (Ad5) variants defective in E1A or E1B. Mutant Adel3 with deletion from E1A was markedly attenuated in permissive cell cultures regardless of the p53 status, and replicated efficiently only in cells of the complementing 293 line. Mutant Adel2 with deletion from E1B55K infected the 293 line cells and p53-deficient human tumor cells (A431, SW480, HEp2) with efficiencies similar to those of Ad5, whereas its replication in normal p53-positive cells was substantially limited. Thus, Adel2 proved to be capable of selective infection and lysis of p53-deficient human tumor cells in vitro. On intratumor injection, Adel2 dramatically suppressed the growth of human epidermoid carcinoma (A431) in nude mice. Adel2 is thus a promising model for designing therapeutic agents against p53-deficient human tumors.     

From identification of genomic polymorphism to diagnostic and prognostic markers of human epithelial tumors

The review considers the results obtained by several groups in the fields of identification of polymorphic loci in the human genome, localization and analysis of genes associated with epithelial tumors of various origins, and generation of molecular markers of socially important oncological diseases. In the first two cases, work was initiated and supported by the Russian program Human Genome. To find new polymorphic loci in the human genome, di-, tri-, and tetranucleotide repeats were searched for in an ordered cosmid library of chromosome 13, NotI and cosmid clones of chromosome 3, and in brain EST. In total, nine polymorphisms and almost 200 STS were identified. Markers of NotI clones of chromosome 3 were associated with particular genes. Polymorphic loci NL1-024, NL2-007, and EST04896 were employed in analysis of deletions from chromosome 3p in tumor DNA. Deletion mapping of 3p in epithelial tumors of five types revealed six critical regions containing potential tumor suppressor genes. Of these, two were in the distal region of chromosome 3p and four, in region 3p21.3. A significant correlation was observed for the frequency of allelic deletions and the stage and the grade of tumors (P < 0.05). On the strength of these findings, genes of region 3p were associated with both tumor development and progression, and proposed as prognostic markers. Regions LUCA and AP20 (3p21.3) showed a high (90%) frequency of aberrations, including homozygous deletions in almost 20% cases. The peak of allelic deletions from region D3S2409-D3S3667 (600 kb) was statistically valid (P = 10(-3)). Regions AP20 and D3S2409-D3S3667 (3p21.3) were for the first time associated with tumorigenesis. Clusters of tumor suppressor genes were identified in regions LUCA, AP20, and D3S2409-D3S3667. Methylation of RASSF1A and RARbeta2 (3p) was associated with early carcinogenesis, and that of SEMA3B, with tumor progression. These findings are useful for early diagnostics and post-surgery prognosis of tumors.     

Tumor angiogenesis inhibitors

Formation of the blood supply system is a critical step in malignant transformation of neoplasms which results in the penetration of tumor cells into neighboring tissues and metastatic growth. Significant progress in the elucidation of mechanisms underlying tumor angiogenesis and the discovery of a great diversity of biomolecules involved in its regulation have culminated in the development of a radically new approach to antitumor therapy based on the search for efficient inhibitors of tumor angiogenesis. This review is devoted to the analysis of action mechanisms and expression of the major endogenous inhibitors involved in regulation of tumor and physiological angiogenesis. The antiangiogenic effects of the majority of currently known synthetic inhibitors are considered in the context of their roles in the main steps of tumor angiogenesis. Possible applications of antiangiogenic therapy in the chemotherapy of cancer diseases are discussed.