207 research outputs found

    Budgeting for Environmental Health Services in Healthcare Facilities: A Ten-Step Model for Planning and Costing

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    Environmental health services (EHS) in healthcare facilities (HCFs) are critical for safe care provision, yet their availability in low- and middle-income countries is low. A poor understanding of costs hinders progress towards adequate provision. Methods are inconsistent and poorly documented in costing literature, suggesting opportunities to improve evidence. The goal of this research was to develop a model to guide budgeting for EHS in HCFs. Based on 47 studies selected through a systematic review, we identified discrete budgeting steps, developed codes to define each step, and ordered steps into a model. We identified good practices based on a review of additional selected guidelines for costing EHS and HCFs. Our model comprises ten steps in three phases: planning, data collection, and synthesis. Costing-stakeholders define the costing purpose, relevant EHS, and cost scope; assess the EHS delivery context; develop a costing plan; and identify data sources (planning). Stakeholders then execute their costing plan and evaluate the data quality (data collection). Finally, stakeholders calculate costs and disseminate findings (synthesis). We present three hypothetical costing examples and discuss good practices, including using costing frameworks, selecting appropriate indicators to measure the quantity and quality of EHS, and iterating planning and data collection to select appropriate costing approaches and identify data gaps

    Effects of the glucolipid synthase inhibitor, P4, on functional and phenotypic parameters of murine myeloma cells

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    This study describes the effects of the glucolipid synthase inhibitor P4, (DL-threo-1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol), on various functional and phenotypic parameters of 5T33 murine myeloma cells. Cell recovery was reduced by >85% following incubation of the cells for 3 days in the presence of 4 μM P4 (the IC50 concentration). Both cytostatic and cytotoxic inhibition was observed with tumour cell metabolic activity and clonogenic potential reduced to 42% and 14% of controls, respectively, and viability reduced to 52%. A dose-dependent increase in cells undergoing apoptosis (from 7% to 26%) was also found. P4 induced a decrease in the number of cells expressing H-2 Class I and CD44, and a large increase in cells expressing H-2 Class II and the IgG2b paraprotein. It did not affect surface expression of CD45 or CD54 (ICAM-1). Based on these alterations in tumour cell growth, adhesion molecule expression and potential immunogenicity, it is anticipated that P4 will provide a novel therapeutic approach for the treatment of multiple myeloma. In addition, given that essentially all tumours rely heavily on overexpressed or abnormal glucosphingolipids for growth, development and metastasis, glucolipid synthase inhibitors may prove to be universally effective anti-cancer agents. © 1999 Cancer Research Campaig

    Osteochondral defects in the ankle: why painful?

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    Osteochondral defects of the ankle can either heal and remain asymptomatic or progress to deep ankle pain on weight bearing and formation of subchondral bone cysts. The development of a symptomatic OD depends on various factors, including the damage and insufficient repair of the subchondral bone plate. The ankle joint has a high congruency. During loading, compressed cartilage forces its water into the microfractured subchondral bone, leading to a localized high increased flow and pressure of fluid in the subchondral bone. This will result in local osteolysis and can explain the slow development of a subchondral cyst. The pain does not arise from the cartilage lesion, but is most probably caused by repetitive high fluid pressure during walking, which results in stimulation of the highly innervated subchondral bone underneath the cartilage defect. Understanding the natural history of osteochondral defects could lead to the development of strategies for preventing progressive joint damage

    MRI texture analysis of subchondral bone at the tibial plateau

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    OBJECTIVES: To determine the feasibility of MRI texture analysis as a method of quantifying subchondral bone architecture in knee osteoarthritis (OA).   METHODS: Asymptomatic subjects aged 20-30 (group 1, n = 10), symptomatic patients aged 40-50 (group 2, n = 10) and patients scheduled for knee replacement aged 55-85 (group 3, n = 10) underwent high spatial resolution T1-weighted coronal 3T knee MRI. Regions of interest were created in the medial (MT) and lateral (LT) tibial subchondral bone from which 20 texture parameters were calculated. T2 mapping of the tibial cartilage was performed in groups 1 and 2. Mean parameter values were compared between groups using ANOVA. Linear discriminant analysis (LDA) was used to evaluate the ability of texture analysis to classify subjects correctly.   RESULTS: Significant differences in 18/20 and 12/20 subchondral bone texture parameters were demonstrated between groups at the MT and LT respectively. There was no significant difference in mean MT or LT cartilage T2 values between group 1 and group 2. LDA demonstrated subject classification accuracy of 97 % (95 % CI 91-100 %).   CONCLUSION: MRI texture analysis of tibial subchondral bone may allow detection of alteration in subchondral bone architecture in OA. This has potential applications in understanding OA pathogenesis and assessing response to treatment.   KEY POINTS: • Improved techniques to monitor OA disease progression and treatment response are desirable • Subchondral bone (SB) may play significant role in the development of OA • MRI texture analysis is a method of quantifying changes in SB architecture • Pilot study showed that this technique is feasible and reliable • Significant differences in SB texture were demonstrated between individuals with/without OA

    Molecular changes in articular cartilage and subchondral bone in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis

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    <p>Abstract</p> <p>Background</p> <p>Osteoarthritis (OA) is a debilitating, progressive joint disease.</p> <p>Methods</p> <p>Similar to the disease progression in humans, sequential events of early cartilage degradation, subchondral osteopenia followed by sclerosis, and late osteophyte formation were demonstrated in the anterior cruciate ligament transection (ACLT) or ACLT with partial medial meniscectomy (ACLT + MMx) rat OA models. We describe a reliable and consistent method to examine the time dependent changes in the gene expression profiles in articular cartilage and subchondral bone.</p> <p>Results</p> <p>Local regulation of matrix degradation markers was demonstrated by a significant increase in mRNA levels of aggrecanase-1 and MMP-13 as early as the first week post-surgery, and expression remained elevated throughout the 10 week study. Immunohistochemistry confirmed MMP-13 expression in differentiated chondrocytes and synovial fibroblasts at week-2 and cells within osteophytes at week-10 in the surgically-modified-joints. Concomitant increases in chondrocyte differentiation markers, Col IIA and Sox 9, and vascular invasion markers, VEGF and CD31, peaked around week-2 to -4, and returned to Sham levels at later time points in both models. Indeed, VEGF-positive cells were found in the deep articular chondrocytes adjacent to subchondral bone. Osteoclastic bone resorption markers, cathepsin K and TRAP, were also elevated at week-2. Confirming bone resorption is an early local event in OA progression, cathepsin K positive osteoclasts were found invading the articular cartilage from the subchondral region at week 2. This was followed by late disease events, including subchondral sclerosis and osteophyte formation, as demonstrated by the upregulation of the osteoanabolic markers runx2 and osterix, toward week-4 to 6 post-surgery.</p> <p>Conclusions</p> <p>In summary, this study demonstrated the temporal and cohesive gene expression changes in articular cartilage and subchondral bone using known markers of OA progression. The findings here support genome-wide profiling efforts to elucidate the sequential and complex regulation of the disease.</p

    Basic science of osteoarthritis

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    Osteoarthritis (OA) is a prevalent, disabling disorder of the joints that affects a large population worldwide and for which there is no definitive cure. This review provides critical insights into the basic knowledge on OA that may lead to innovative end efficient new therapeutic regimens. While degradation of the articular cartilage is the hallmark of OA, with altered interactions between chondrocytes and compounds of the extracellular matrix, the subchondral bone has been also described as a key component of the disease, involving specific pathomechanisms controlling its initiation and progression. The identification of such events (and thus of possible targets for therapy) has been made possible by the availability of a number of animal models that aim at reproducing the human pathology, in particular large models of high tibial osteotomy (HTO). From a therapeutic point of view, mesenchymal stem cells (MSCs) represent a promising option for the treatment of OA and may be used concomitantly with functional substitutes integrating scaffolds and drugs/growth factors in tissue engineering setups. Altogether, these advances in the fundamental and experimental knowledge on OA may allow for the generation of improved, adapted therapeutic regimens to treat human OA.(undefined

    Enhancing Biological and Biomechanical Fixation of Osteochondral Scaffold: A Grand Challenge

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    Osteoarthritis (OA) is a degenerative joint disease, typified by degradation of cartilage and changes in the subchondral bone, resulting in pain, stiffness and reduced mobility. Current surgical treatments often fail to regenerate hyaline cartilage and result in the formation of fibrocartilage. Tissue engineering approaches have emerged for the repair of cartilage defects and damages to the subchondral bones in the early stage of OA and have shown potential in restoring the joint's function. In this approach, the use of three-dimensional scaffolds (with or without cells) provides support for tissue growth. Commercially available osteochondral (OC) scaffolds have been studied in OA patients for repair and regeneration of OC defects. However, some controversial results are often reported from both clinical trials and animal studies. The objective of this chapter is to report the scaffolds clinical requirements and performance of the currently available OC scaffolds that have been investigated both in animal studies and in clinical trials. The findings have demonstrated the importance of biological and biomechanical fixation of the OC scaffolds in achieving good cartilage fill and improved hyaline cartilage formation. It is concluded that improving cartilage fill, enhancing its integration with host tissues and achieving a strong and stable subchondral bone support for overlying cartilage are still grand challenges for the early treatment of OA

    Heuristics for practitioners of policy design: Rules-of-thumb for structuring unstructured problems

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    This article is an attempt to bridge the divide between academics and practitioners. Informed by both design theory and the reality of policy work, its focus is on ‘problems’. From a practitioners’ perspective, policy design is both an intellectual and political process, an inevitable oscillation between ‘puzzling’ and ‘powering’, in which ‘messy’ or unstructured problems are re-structured from problems as webs of ‘undesirable situations’ to problems as specific, time-and-space bound ‘opportunities for improve- ment’. This requires a questioning habitus in practitioners of policy design. Using a socio-cognitive theory of problem processing, this paper shows how policy design is an iterative process of problem sensing, problem categorization, problem decompos- ition and problem definition. For each of these stages, appropriate rules-of-thumb for questioning and answering can be suggested that induce thought habits and styles for responsive and solid policy designs

    Basic Science Considerations in Primary Total Hip Replacement Arthroplasty

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    Total Hip Replacement is one of the most common operations performed in the developed world today. An increasingly ageing population means that the numbers of people undergoing this operation is set to rise. There are a numerous number of prosthesis on the market and it is often difficult to choose between them. It is therefore necessary to have a good understanding of the basic scientific principles in Total Hip Replacement and the evidence base underpinning them. This paper reviews the relevant anatomical and biomechanical principles in THA. It goes on to elaborate on the structural properties of materials used in modern implants and looks at the evidence base for different types of fixation including cemented and uncemented components. Modern bearing surfaces are discussed in addition to the scientific basis of various surface engineering modifications in THA prostheses. The basic science considerations in component alignment and abductor tension are also discussed. A brief discussion on modular and custom designs of THR is also included. This article reviews basic science concepts and the rationale underpinning the use of the femoral and acetabular component in total hip replacement
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