Strengthening patient-centred communication in rural Ugandan health centres: A theory-driven evaluation within a cluster randomized trial.

This article describes a theory-driven evaluation of one component of an intervention to improve the quality of health care at Ugandan public health centres. Patient-centred services have been advocated widely, but such approaches have received little attention in Africa. A cluster randomized trial is evaluating population-level outcomes of an intervention with multiple components, including 'patient-centred services.' A process evaluation was designed within this trial to articulate and evaluate the implementation and programme theories of the intervention. This article evaluates one hypothesized mechanism of change within the programme theory: the impact of the Patient Centred Services component on health-worker communication. The theory-driven approach extended to evaluation of the outcome measures. The study found that the proximal outcome of patient-centred communication was rated 10 percent higher (p < 0.008) by care seekers consulting with the health workers who were at the intervention health centres compared with those at control health centres. This finding will strengthen interpretation of more distal trial outcomes

Identification of the initial molecular changes in response to circulating angiogenic cells-mediated therapy in critical limb ischemia

BackgroundCritical limb ischemia (CLI) constitutes the most aggressive form of peripheral arterial occlusive disease, characterized by the blockade of arteries supplying blood to the lower extremities, significantly diminishing oxygen and nutrient supply. CLI patients usually undergo amputation of fingers, feet, or extremities, with a high risk of mortality due to associated comorbidities.Circulating angiogenic cells (CACs), also known as early endothelial progenitor cells, constitute promising candidates for cell therapy in CLI due to their assigned vascular regenerative properties. Preclinical and clinical assays with CACs have shown promising results. A better understanding of how these cells participate in vascular regeneration would significantly help to potentiate their role in revascularization.Herein, we analyzed the initial molecular mechanisms triggered by human CACs after being administered to a murine model of CLI, in order to understand how these cells promote angiogenesis within the ischemic tissues.MethodsBalb-c nude mice (n:24) were distributed in four different groups: healthy controls (C, n:4), shams (SH, n:4), and ischemic mice (after femoral ligation) that received either 50 mu l physiological serum (SC, n:8) or 5x10(5) human CACs (SE, n:8). Ischemic mice were sacrificed on days 2 and 4 (n:4/group/day), and immunohistochemistry assays and qPCR amplification of Alu-human-specific sequences were carried out for cell detection and vascular density measurements. Additionally, a label-free MS-based quantitative approach was performed to identify protein changes related.ResultsAdministration of CACs induced in the ischemic tissues an increase in the number of blood vessels as well as the diameter size compared to ischemic, non-treated mice, although the number of CACs decreased within time. The initial protein changes taking place in response to ischemia and more importantly, right after administration of CACs to CLI mice, are shown.ConclusionsOur results indicate that CACs migrate to the injured area; moreover, they trigger protein changes correlated with cell migration, cell death, angiogenesis, and arteriogenesis in the host. These changes indicate that CACs promote from the beginning an increase in the number of vessels as well as the development of an appropriate vascular network.Institute of Health Carlos III, ISCIII; Junta de Andaluci

Contribution mapping: a method for mapping the contribution of research to enhance its impact.

Background: At a time of growing emphasis on both the use of research and accountability, it is important for research funders, researchers and other stakeholders to monitor and evaluate the extent to which research contributes to better action for health, and find ways to enhance the likelihood that beneficial contributions are realized. Past attempts to assess research 'impact' struggle with operationalizing 'impact', identifying the users of research and attributing impact to research projects as source. In this article we describe Contribution Mapping, a novel approach to research monitoring and evaluation that aims to assess contributions instead of impacts. The approach focuses on processes and actors and systematically assesses anticipatory efforts that aim to enhance contributions, so-called alignment efforts. The approach is designed to be useful for both accountability purposes and for assisting in better employing research to contribute to better action for health.Methods: Contribution Mapping is inspired by a perspective from social studies of science on how research and knowledge utilization processes evolve. For each research project that is assessed, a three-phase process map is developed that includes the main actors, activities and alignment efforts during research formulation, production and knowledge extension (e.g. dissemination and utilization). The approach focuses on the actors involved in, or interacting with, a research project (the linked actors) and the most likely influential users, who are referred to as potential key users. In the first stage, the investigators of the assessed project are interviewed to develop a preliminary version of the process map and first estimation of research-related contributions. In the second stage, potential key-users and other informants are interviewed to trace, explore and triangulate possible contributions. In the third stage, the presence and role of alignment efforts is analyzed and the preliminary results are shared with relevant stakeholders for feedback and validation. After inconsistencies are clarified or described, the results are shared with stakeholders for learning, improvement and accountability purposes.Conclusion: Contribution Mapping provides an interesting alternative to existing methods that aim to assess research impact. The method is expected to be useful for research monitoring, single case studies, comparing multiple cases and indicating how research can better be employed to contribute to better action for health. © 2012 Kok and Schuit; licensee BioMed Central Ltd

Collateral circulation: Past and present

Following an arterial occlusion outward remodeling of pre-existent inter-connecting arterioles occurs by proliferation of vascular smooth muscle and endothelial cells. This is initiated by deformation of the endothelial cells through increased pulsatile fluid shear stress (FSS) caused by the steep pressure gradient between the high pre-occlusive and the very low post-occlusive pressure regions that are interconnected by collateral vessels. Shear stress leads to the activation and expression of all NOS isoforms and NO production, followed by endothelial VEGF secretion, which induces MCP-1 synthesis in endothelium and in the smooth muscle of the media. This leads to attraction and activation of monocytes and T-cells into the adventitial space (peripheral collateral vessels) or attachment of these cells to the endothelium (coronary collaterals). Mononuclear cells produce proteases and growth factors to digest the extra-cellular scaffold and allow motility and provide space for the new cells. They also produce NO from iNOS, which is essential for arteriogenesis. The bulk of new tissue production is carried by the smooth muscles of the media, which transform their phenotype from a contractile into a synthetic and proliferative one. Important roles are played by actin binding proteins like ABRA, cofilin, and thymosin beta 4 which determine actin polymerization and maturation. Integrins and connexins are markedly up-regulated. A key role in this concerted action which leads to a 2-to-20 fold increase in vascular diameter, depending on species size (mouse versus human) are the transcription factors AP-1, egr-1, carp, ets, by the Rho pathway and by the Mitogen Activated Kinases ERK-1 and -2. In spite of the enormous increase in tissue mass (up to 50-fold) the degree of functional restoration of blood flow capacity is incomplete and ends at 30% of maximal conductance (coronary) and 40% in the vascular periphery. The process of arteriogenesis can be drastically stimulated by increases in FSS (arterio-venous fistulas) and can be completely blocked by inhibition of NO production, by pharmacological blockade of VEGF-A and by the inhibition of the Rho-pathway. Pharmacological stimulation of arteriogenesis, important for the treatment of arterial occlusive diseases, seems feasible with NO donors

Immunoglobulins in chronic renal failure of childhood: effects of dialysis modalities

Immunoglobulins in chronic renal failure of childhood: Effects of dialysis modalities.BackgroundIt is not clear whether low serum levels of IgG (subclasses), previously demonstrated in children on peritoneal dialysis (PD), are related to the PD procedure or to factors associated with chronic renal failure (CRF). The aim of our study was to analyze the effect of PD on serum and PD effluent (PDE) IgG and subclass levels in children with end-stage renal failure.MethodsWe measured albumin, IgG, IgA, IgM, and IgG subclasses in serum and PDE from children on PD (N = 40) and compared the serum values with those of children treated with hemodialysis (HD, N = 23) or presenting with CRF but not yet dialyzed (CRF; N = 63), and with a group of healthy controls (HCs; N = 67). Sixteen PD children could be followed sequentially from before starting PD and eight during a peritonitis episode.ResultsForty percent of the PD children showed reduced serum IgG2 levels (P = 0.0003) compared with 35% in HD (P = 0.006), 33% in CRF (P = 0.001), and 9% in HC children. IgG1 deficiencies were observed in 25% of PD patients (P < 0.0001), 4% of HD (P = NS), 16% of CRF (P = 0.0005), and 0% of HC children. IgG3 and IgG4 deficiencies were observed less frequently. Peritoneal clearances were similar for total IgG, IgG1, IgG2, and IgG4, but were lower for IgG3 (P < 0.05). No relationships were found between clearances and age or duration of PD treatment. Total IgG (P = 0.003) and IgG1 (P = 0.002) levels declined just after starting PD. Peritonitis was associated with temporarily increased peritoneal loss of Ig, while the serum concentrations were unaffected. No significant relationship was found between the peritonitis incidence and reduced IgG or subclasses. However, all children with two or more peritonitis episodes per year had a reduced Ig level.ConclusionsAlthough the mean serum concentrations of immunoglobulins were normal in all studied groups, a deficiency of one or more IgG subclasses was present in all groups with renal failure, suggesting inhibition of their synthesis by the uremic state. Ig deficiencies were more frequently found in PD, likely caused by protein loss in PDE. A high peritonitis incidence was associated with reduced serum Ig levels

Allogeneic stem cell transplantation for Fanconi anaemia

Fanconi anaemia is a hereditary disorder characterised by chromosomal breaks increased by cross-linking agents. Bone marrow transplantation is the treatment of choice when a HLA identical sibling donor has been identified. The use of low-dose cyclophosphamide with thoraco-abdominal irradiation for the conditioning regimen of FA patients has lead to a dramatic improvement of survival, with a long-term survival of 75% at our institution. However, if most patients are completely cured of their haematological disease, there is concern about an increased frequency of secondary tumours, mostly head and neck squamous cell carcinomas of poor prognosis. Results of BMT using alternative donors (HLA mismatched related and unrelated donors) have also improved during the last decade. A better selection of the donor via high-resolution techniques for class-II HLA matching, and more recently the use of T cell depleted grafts are probably the main explanations. Despite a short follow-up and the small number of patients analysed, transplants using HLA matched family cord blood give some promising results. On the other hand, first results with unrelated cord blood remind that this approach is clearly an experimental one that has to be evaluated through international registries and prospective studies. New approaches including autologous stem cell transplantations and gene therapy are currently explored

Geriatric rehabilitation of stroke patients in nursing homes: a study protocol.

Contains fulltext : 88482.pdf (publisher's version ) (Open Access)BACKGROUND: Geriatric patients are typically underrepresented in studies on the functional outcome of rehabilitation after stroke. Moreover, most geriatric stroke patients do probably not participate in intensive rehabilitation programs as offered by rehabilitation centers. As a result, very few studies have described the successfulness of geriatric stroke rehabilitation in nursing home patients, although it appears that the majority of these patients are being discharged back to the community, rather than being transferred to residential care. Nevertheless, factors associated with the successfulness of stroke rehabilitation in nursing homes or skilled nursing facilities are largely unknown. The primary goal of this study is, therefore, to assess the factors that uniquely contribute to the successfulness of rehabilitation in geriatric stroke patients that undergo rehabilitation in nursing homes. A secondary goal is to investigate whether these factors are similar to those associated with the outcome of stroke rehabilitation in the literature. METHODS/DESIGN: This study is part of the Geriatric Rehabilitation in AMPutation and Stroke (GRAMPS) study in the Netherlands. It is a longitudinal, observational, multicenter study in 15 nursing homes in the Southern part of the Netherlands that aims to include at least 200 patients. All participating nursing homes are selected based on the existence of a specialized rehabilitation unit and the provision of dedicated multidisciplinary care. Patient characteristics, disease characteristics, functional status, cognition, behavior, and caregiver information, are collected within two weeks after admission to the nursing home. The first follow-up is at discharge from the nursing home or one year after inclusion, and focuses on functional status and behavior. Successful rehabilitation is defined as discharge from the nursing home to an independent living situation within one year after admission. The second follow-up is three months after discharge in patients who rehabilitated successfully, and assesses functional status, behavior, and quality of life. All instruments used in this study have shown to be valid and reliable in rehabilitation research or are recommended by the Netherlands Heart Foundation guidelines for stroke rehabilitation.Data will be analyzed using SPSS 16.0. Besides descriptive analyses, both univariate and multivariate analyses will be performed with the purpose of identifying associated factors as well as their unique contribution to determining successful rehabilitation. DISCUSSION: This study will provide more information about geriatric stroke rehabilitation in Dutch nursing homes. To our knowledge, this is the first large study that focuses on the determinants of success of geriatric stroke rehabilitation in nursing home patients