[A multi-centre ROM study of the Guideline-Informed Treatment for Personality Disorders]. / Een ROM-studie van de Guideline-Informed Treatment for Personality Disorders in vier behandelcentra.

BACKGROUND: The Guideline-Informed Treatment for Personality Disorders (GIT-PD) is widely used in the Netherlands and Belgium in the care of people with personality disorders. To date, no evidence existed for the possible efficacy of this treatment framework.  METHOD: In an observational cohort study in four institutions, based on Routine Outcome Monitoring-data, improvements in symptom burden (BSI/OQ-45) and personality functioning (SIPP-SF) in 470 patients were examined.  RESULTS: Significant improvements were observed in each of the settings for both symptom burden and personality functioning. Effect sizes for improvement in overall symptom burden ranged from d = 0.55 to 1.05.  CONCLUSION: Treatment outcomes for GIT-PD are in line with treatment outcomes also seen for specialized treatments for personality disorders in similar practice studies. Possible differences between settings could be related to the intensity, structure and coherence of the GIT-PD program in question. .

[How evidence-based is the guideline-informed treatment for personality disorders (GIT-PD)?] / Hoe bewezen effectief is de guideline-informed treatment for personality disorders (GIT-PD)?

BACKGROUND: The guideline-informed treatment for personality disorders (GIT-PD) was developed as an alternative to the specific treatments for personality disorders. Even though this form of treatment is widely used in health care and has been included in the Health Care Standard for Personality Disorders, its scientific evidence remains unclear. AIM: To review the indirect evidence for GIT-PD and compare it with the evidence for specific treatments. METHOD: Literature review including reviews and meta-analyses in the field of personality disorders. RESULTS: Although there is increasing evidence for specific treatments, the amount of studies remains limited and the quality of the evidence is rather low. There are indications that specific treatments are poorly implemented in clinical practice, which may detract from their efficacy. There is no clear evidence that specific treatments are on average no more effective than well-designed generic treatments that are similar to GIT-PD. There is considerable evidence for the role of the common factors on which GIT-PD is based. CONCLUSION: There is indirect evidence for the efficacy of GIT-PD. Good care on a broad scale needs both specific and generic forms of treatment, whereby the most relevant question becomes how clients can be optimally allocated to both forms of treatment.

Cutaneous wound analysis using hyperspectral imaging.

A correlative bright-field and hyperspectral analysis of full-thickness, cutaneous wounds in a porcine model was undertaken to investigate the efficacy of hyperspectral imaging as an alternate method for wound identification. Analysis of a randomly selected specimen yielded distinct spectral signatures for cutaneous regions of interest including the epidermis, injured dermis, and normal dermis. The scanning of the entire specimen group using these hyperspectral signatures revealed an exclusionary, pseudo-color pattern whereby a central wound region was consistently defined by a unique spectral signature. An algorithm was derived as an objective tool for the comparison of the wound regions defined by the hyperspectral classification versus the pathologists' manual tracings. The dimensions of the wound identified in the hyperspectral assay did not differ significantly from the wound region identified by the pathologists using standard bright-field microscopy. These data indicate that hyperspectral analysis may provide a high-throughput alternative for wound estimation that approximates standard bright-field imaging and pathologist evaluation.

Effects of carbodiimide crosslinking conditions on the physical properties of laminated intestinal submucosa.

Functional tissue engineering of load-bearing repair tissues requires the design and production of biomaterials that provide a remodelable scaffold for host infiltration and tissue regeneration while maintaining the repair function throughout the remodeling process. Layered constructs have been fabricated from chemically and mechanically cleaned porcine intestinal collagen using ethyl-3(3-dimethylamino) propyl carbodiimide (EDC) and an acetone solvent. By varying the concentration of the crosslinker from 1 to 10 mM and the solvent from 0 to 90% acetone, the strength, stiffness, maximum strain, thermal stability, lamination strength, and suture retention strength can be adjusted. These parameters have either functional importance or the potential to modify the remodeling kinetics, or they have both. This study investigates the interdependence of these parameters, the specific effects that variations in concentration can achieve, and how the two crosslinking variables interact. The results demonstrate that there is substantial latitude in the design of these constructs by these straightforward crosslinking modifications. These data provide the basis for studying the in vivo response to crosslinking conditions that will supply the requisite strength while still allowing host cell infiltration and remodeling.

Mechanical evaluation and design of a multilayered collagenous repair biomaterial.

One method of fabricating implantable biomaterials is to utilize biologically derived, chemically modified tissues to form constructs that are both biocompatible and remodelable. Rigorous mechanical characterization is a necessary component in material evaluation to ensure that the constructs will withstand in vivo loading. In this study we performed an in-depth biaxial mechanical and quantitative structural analysis of GraftPatch (GP), a biomaterial constructed by assembling chemically treated layers of porcine small intestinal submucosa (SIS). The mechanical behavior of GP was compared to both native SIS and to glutaraldehyde-treated bovine pericardium (GLBP) as a reference biomaterial. Under biaxial loading, GP was found to be stiffer than native SIS and mechanically anisotropic, with the preferred fiber direction demonstrating greater stiffness. Quantitative structural analysis using small-angle light scattering indicated a uniform fiber structure similar to GLBP and SIS. To enable test-protocol-independent quantitative comparisons, the biaxial mechanical data were fit to an orthotropic constitutive model, which indicated a similar degree of mechanical anisotropy between the three groups. We also demonstrate how the constitutive model can be used to design layered biocomposite materials that can undergo large deformations.

A novel injectable collagen matrix: in vitro characterization and in vivo evaluation.

We present here a unique engineered collagen formulation that is injectable and compacts into a porous viscoelastic solid after implantation, achieving completely focal application without cross-linking. This implant provides a cohesive continuously porous matrix, as demonstrated by permeability and compression experiments. Those experiments also provide initial mechanical characterization of the material and establish the ability to modify these essential properties by design. Further, the short-term compaction and long-term stability of the implant in vivo in terms of both physical and histological responses are assessed in an animal model to demonstrate the mechanism of action and long-term persistence of this novel material.

Incompressibility of the solid matrix of articular cartilage under high hydrostatic pressures.

The objective of this study was to test the hypothesis that the organic solid matrix of articular cartilage is incompressible under physiological levels of pressure. Due to its anisotropic swelling behavior, an anisotropic version of the biphasic theory was used to predict the deformation and internal stress fields. This theory predicts that, under hydrostatic loading of cartilage via a pressurized external fluid, a state of uniform hydrostatic fluid pressure exists within the tissue regardless of the anisotropic nature of the solid matrix. The theory also predicts that if the solid matrix is intrinsically incompressible, the tissue will not deform under hydrostatic loading conditions. This prediction, i.e., no deformation, was experimentally tested by subjecting specimens of normal bovine articular cartilage to hydrostatic pressures. A new high pressure hydrostatic loading chamber was designed and built for this purpose. It was found that normal bovine articular cartilage, when subject to hydrostatic pressures up to 12 M Pa, does not deform measurably. This experimental finding supports one of the fundamental assumptions of the biphasic theory for cartilage, i.e., the organic solid matrix of the tissue is intrinsically incompressible when loaded within the normal physiologic range of pressures. Hydrostatic loading has often heen used in cartilage explant cultures for tissue metabolism studies. The findings of this study provides an accurate method to calculate the states of stress acting on the fluid and solid phases of the tissue in these hydrostatically loaded explant culture experiments, and suggest that tissue deformation will be minimal under pure hydrostatic pressurization.

Load-controlled compression of articular cartilage induces a transient stimulation of aggrecan gene expression.

The effects of short- and long-term load-controlled compression on the levels of aggrecan mRNA have been determined. Results show that a compressive stress of 0.1 MPa on bovine articular cartilage explants for 1, 4, 12, and 24 h produces a transient up-regulation of aggrecan mRNA synthesis. At 1 h, aggrecan mRNA levels in loaded explants were increased 3.2-fold compared to control explants. At longer times (>/=4 h), the levels of aggrecan mRNA returned to baseline values or stayed slightly higher. There is a dose dependence in the response of the explant to increasing levels of compressive stress (0-0.5 MPa) for 1 h. Aggrecan mRNA levels increased 2- to 3-fold at 0-0.25 MPa. At 0.5 MPa, the level of aggrecan mRNA was lower than those at 0.1 and 0.25 MPa. This dose-dependent effect suggests a reversal of the stimulatory effects of compression on aggrecan gene expression at higher loads. After 24 h of compression, the levels of aggrecan mRNA in explants subjected to any of the stress levels were not significantly different from those in control explants. The stimulatory effect of 0.1 MPa compressive stress on aggrecan mRNA levels was blocked by Rp-cAMP and U-73122, indicating the involvement of the classical signal transduction pathways in the mechanical modulation of aggrecan gene expression. The responses of link protein mRNA to compression paralleled those of aggrecan, while there was no significant change in expression of the gene for the housekeeping protein elongation factor-1 alpha. The results indicate that articular cartilage chondrocytes can respond to short-term compressive loads by transiently up-regulating expression of the aggrecan gene. The fact that long-term compression did not significantly alter aggrecan mRNA levels suggests that previously observed inhibitory effects of prolonged static compression on proteoglycan synthesis in articular cartilage may be, for the most part, mediated through mechanisms other than suppression of aggrecan mRNA levels.

Changes in proteoglycan synthesis of chondrocytes in articular cartilage are associated with the time-dependent changes in their mechanical environment.

Explant loading experiments were conducted to investigate the effect of load duration on proteoglycan synthesis. A compressive load of 0.1 MPa applied for 10 min was found to stimulate proteoglycan synthesis, while the same load applied for 20 h suppressed synthesis. This bimodal response suggests that the cells are responding to different mechanical stimuli as time progresses. A theoretical model has therefore been developed to describe the mechanical environment perceived by cells within soft hydrated tissues (e.g. articular cartilage) while the tissue is being loaded. The cells are modeled, using the biphasic theory, as fluid-solid inclusions embedded in and attached to a biphasic extracellular matrix of distinct material properties. A method of solution is developed which is valid for any axisymmetric loading configuration, provided that the cell radius, a, is small relative to the tissue height, h (i.e. h/a >> 1). A closed-form analytical solution for this inclusion problem is then presented for the confined compression configuration. Results from this model show that the mechanical environment in and around the cells is time dependent and inhomogeneous, and can be significantly influenced by differences in properties between the cell and the extracellular matrix.