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1.
Health Res Policy Syst ; 21(1): 106, 2023 Oct 17.
Article in English | MEDLINE | ID: mdl-37848923

ABSTRACT

BACKGROUND: Population health management (PHM) initiatives are more frequently implemented as a means to tackle the growing pressure on healthcare systems in Western countries. These initiatives aim to transform healthcare systems into sustainable health and wellbeing systems. International studies have already identified guiding principles to aid this development. However, translating this knowledge to action remains a challenge. To help address this challenge, the study aims to identify program managers' experiences and their expectations as to the use of this knowledge to support the development process of PHM initiatives. METHODS: Semi-structured interviews were held with program managers of ten Dutch PHM initiatives. These Dutch PHM initiatives were all part of a reflexive evaluation study and were selected on the basis of their variety in focus and involved stakeholders. Program managers were asked about their experiences with, and expectations towards, knowledge use to support the development of their initiative. The interviews with the program managers were coded and clustered thematically. RESULTS: Three lessons for knowledge use for the development of PHM initiatives were identified: (1) being able to use knowledge regarding the complexity of PHM development requires (external) expertise regarding PHM development and knowledge about the local situation regarding these themes; (2) the dissemination of knowledge about strategies for PHM development requires better guidance for action, by providing more practical examples of actions and consequences; (3) a collective learning process within the PHM initiative is needed to support knowledge being successfully used for action. CONCLUSIONS: Disseminating and using knowledge to aid PHM initiatives is complex due to the complexity of the PHM development itself, and the different contextual factors affecting knowledge use in this development. The findings in this study suggest that for empirical knowledge to support PHM development, tailoring knowledge to only program managers' use might be insufficient to support the initiatives' development, as urgency for change amongst the other involved stakeholders is needed to translate knowledge to action. Therefore, including more partners of the initiatives in knowledge dissemination and mobilization processes is advised.


Subject(s)
Population Health Management , Humans , Qualitative Research , Delivery of Health Care , Learning
3.
Front Immunol ; 14: 1122409, 2023.
Article in English | MEDLINE | ID: mdl-36891297

ABSTRACT

Mast cells (MCs) are innate immune cells with a versatile set of functionalities, enabling them to orchestrate immune responses in various ways. Aside from their known role in allergy, they also partake in both allograft tolerance and rejection through interaction with regulatory T cells, effector T cells, B cells and degranulation of cytokines and other mediators. MC mediators have both pro- and anti-inflammatory actions, but overall lean towards pro-fibrotic pathways. Paradoxically, they are also seen as having potential protective effects in tissue remodeling post-injury. This manuscript elaborates on current knowledge of the functional diversity of mast cells in kidney transplants, combining theory and practice into a MC model stipulating both protective and harmful capabilities in the kidney transplant setting.


Subject(s)
Hypersensitivity , Kidney Transplantation , Humans , Mast Cells , Cytokines/metabolism , T-Lymphocytes, Regulatory/metabolism
4.
BMC Health Serv Res ; 23(1): 125, 2023 Feb 07.
Article in English | MEDLINE | ID: mdl-36750839

ABSTRACT

BACKGROUND: Childhood obesity is a complex disease resulting from the interaction of multiple factors. The effective management of childhood obesity requires assessing the psychosocial and lifestyle factors that may play a role in the development and maintenance of obesity. This study centers on available scientific literature on psychosocial and lifestyle assessments for childhood obesity, and experiences and views of healthcare professionals with regard to assessing psychosocial and lifestyle factors within Dutch integrated care. METHODS: Two methods were used. First, a scoping review (in PubMed, Embase, PsycInfo, IBSS, Scopus and Web of Science) was performed by systematically searching for scientific literature on psychosocial and lifestyle assessments for childhood obesity. Data were analysed by extracting data in Microsoft Excel. Second, focus group discussions were held with healthcare professionals from a variety of disciplines and domains to explore their experiences and views about assessing psychosocial and lifestyle factors within Dutch integrated care. Data were analysed using template analysis, complemented with open coding in MAXQDA. RESULTS: The results provide an overview of relevant psychosocial and lifestyle factors that should be assessed and were classified as child, family, parental and lifestyle (e.g. nutrition, physical activity and sleep factors) and structured into psychological and social aspects. Insights into how to assess psychosocial and lifestyle factors were identified as well, including talking about psychosocial factors, lifestyle and weight; the professional-patient relationship; and attitudes of healthcare professionals. CONCLUSIONS: This study provides an overview of psychosocial and lifestyle factors that should be identified within the context of childhood obesity care, as they may contribute to the development and maintenance of obesity. The results highlight the importance of both what is assessed and how it is assessed. The results of this study can be used to develop practical tools for facilitating healthcare professionals in conducting a psychosocial and lifestyle assessment.


Subject(s)
Pediatric Obesity , Humans , Child , Focus Groups , Risk Assessment , Life Style , Delivery of Health Care
5.
BMC Public Health ; 23(1): 67, 2023 01 10.
Article in English | MEDLINE | ID: mdl-36627586

ABSTRACT

BACKGROUND: When improving the health of local and regional populations, cross-sector collaboration between different policy domains, non-governmental organisations and citizens themselves is needed. Previously, enabling factors and strategies have been identified to improve cross-sector collaboration for health. However, few longitudinal studies have been conducted to understand how the implementation of strategies for cross-sector collaboration changes throughout the collaboration process. The aim of this study is therefore to learn more about the different strategies that were implemented throughout three cross-sector collaboration projects for a healthy living environment. METHODS: The realist evaluation approach was used to understand how the implemented strategies worked, in which context, why and with what outcomes. Project partners were asked to reflect on their implemented strategies at two different moments in the project timelines, and quarterly updates with project leaders were held. In addition two reference panels were organised for data triangulation. RESULTS: Three key insights for successful cross-sector collaboration throughout projects for a healthy living environment were identified, namely 1. Investing in trust among the partners and faith in the project has a positive influence on continuing the collaboration throughout the project; 2. Making stakeholders actively participate throughout the project requires additional strategies after the onset of the project, and 3. Defining roles, tasks, and other prerequisites at the start of the project helps in pursuing the project over time, but needs re-examination throughout the project. These key insights were based on multiple examples of implemented strategies, linked to context, mechanisms and outcomes. CONCLUSIONS: This study shows the different strategies that can be employed as the collaboration in projects for a healthy living environment progresses. We found that 'trust' does not merely include the relationships built between the partners, but at the onset of projects can also be based on faith in the project itself. In addition, as it can be difficult to foresee the right investments and strategies at the onset of the project, frequent reflection moments to choose fitting strategies might benefit regional partners in their cross-sector collaboration for health.


Subject(s)
Policy , Trust , Humans , Longitudinal Studies , Healthy Lifestyle
6.
BMC Health Serv Res ; 21(1): 611, 2021 Jun 28.
Article in English | MEDLINE | ID: mdl-34183008

ABSTRACT

BACKGROUND: The causes and consequences of childhood obesity are complex and multifaceted. Therefore, an integrated care approach is required to address weight-related issues and improve children's health, societal participation and quality of life. Conducting a psychosocial and lifestyle assessment is an essential part of an integrated care approach. The aim of this study was to explore the experiences, needs and wishes of healthcare professionals with respect to carrying out a psychosocial and lifestyle assessment of childhood obesity. METHODS: Fourteen semi-structured interviews were conducted with Dutch healthcare professionals, who are responsible for coordinating the support and care for children with obesity (coordinating professionals, 'CPs'). The following topics were addressed in our interviews with these professionals: CPs' experiences of both using childhood obesity assessment tools and their content, and CPs' needs and wishes related to content, circumstances and required competences. The interviews comprised open-ended questions and were recorded and transcribed verbatim. The data was analysed using template analyses and complemented with open coding in MAXQDA. RESULTS: Most CPs experienced both developing a trusting relationship with the children and their parents, as well as establishing the right tone when engaging in weight-related conversations as important. CPs indicated that visual materials were helpful in such conversations. All CPs used a supporting assessment tool to conduct the psychosocial and lifestyle assessment but they also indicated that a more optimal tool was desirable. They recognized the need for specific attributes that helped them to carry out these assessments, namely: sufficient knowledge about the complexity of obesity; having an affinity with obesity-related issues; their experience as a CP; using conversational techniques, such as solution-focused counselling and motivational interviewing; peer-to-peer coaching; and finally, maintaining an open-minded, non-stigmatizing stance and harmonizing their attitude with that of the child and their parents. CONCLUSIONS: Alongside the need for a suitable tool for conducting a psychosocial and lifestyle assessment, CPs expressed the need for requisite knowledge, skills and attitudes. Further developing a supporting assessment tool is necessary in order to facilitate CPs and thereby improve the support and care for children with obesity and their families.


Subject(s)
Delivery of Health Care, Integrated , Pediatric Obesity , Child , Humans , Life Style , Pediatric Obesity/diagnosis , Pediatric Obesity/therapy , Qualitative Research , Quality of Life
7.
Sci Rep ; 11(1): 8915, 2021 04 26.
Article in English | MEDLINE | ID: mdl-33903694

ABSTRACT

The diagnosis of kidney allograft rejection is based on late histological and clinical markers. Early, specific and minimally-invasive biomarkers may improve rejection diagnosis. Endothelial cells (EC) are one of the earliest targets in kidney transplant rejection. We investigated whether circulating EC (cEC) could serve as an earlier and less invasive biomarker for allograft rejection. Blood was collected from a cohort of 51 kidney transplant recipients before and at multiple timepoints after transplantation, including during a for cause biopsy. The number and phenotype of EC was assessed by flow-cytometric analysis. Unbiased selection of EC was done using principal component (PCA) analysis. Paired analysis revealed a transient cEC increase of 2.1-fold on the third day post-transplant, recovering to preoperative levels at seventh day post-transplant and onwards. Analysis of HLA subtype demonstrated that cEC mainly originate from the recipient. cEC levels were not associated with allograft rejection, allograft function or other allograft pathologies. However, cEC in patients with allograft rejection and increased levels of cEC showed elevated levels of KIM-1 (kidney injury marker-1). These findings indicate that cEC numbers and phenotype are affected after kidney transplantation but may not improve rejection diagnosis.


Subject(s)
Endothelial Cells/metabolism , Flow Cytometry , Graft Rejection/blood , Hepatitis A Virus Cellular Receptor 1/blood , Kidney Transplantation , Adult , Allografts , Female , Humans , Male , Middle Aged , Time Factors
8.
BMC Public Health ; 20(1): 508, 2020 Apr 16.
Article in English | MEDLINE | ID: mdl-32299398

ABSTRACT

BACKGROUND: Community engagement is increasingly seen as key to improving healthcare systems and to increasing communities' involvement in the shaping of their own communities. This paper describes how 'community engagement' (CE) is understood and being operationalised in the Dutch healthcare system by investigating the CE approaches being implemented in six different regions and by examining engaged citizens' and professionals' experiences of those CE approaches. METHODS: For this realist study, interviews and focus groups were held with citizens (16) and professionals (42) involved in CE approaches in the six regions. Additionally, CE-related activities were observed to supplement interview data. RESULTS: This study shows that citizens and professionals defined and experienced CE differently and that they differed in who they felt had ownership of CE. The CE approaches implemented in community-led initiatives and organisationally-led initiatives varied accordingly. Furthermore, both citizens and professionals were searching for meaningful ways for citizens to have more control over healthcare in their own communities. CONCLUSION: CE can be improved by, first of all, developing a shared and overarching vision of what CE should look like, establishing clear roles and remits for organisations and communities, and taking active measures to ensure CE is more inclusive and representative of harder-to-reach groups. At the same time, to help ensure such shared visions do not further entrench power imbalances between citizens and professionals, professionals require training in successful CE approaches.


Subject(s)
Community Participation/statistics & numerical data , Community-Based Participatory Research/organization & administration , Health Services Needs and Demand/statistics & numerical data , Cooperative Behavior , Delivery of Health Care , Ethnicity/statistics & numerical data , Focus Groups , Humans , Netherlands , Qualitative Research , Socioeconomic Factors
10.
Health Policy ; 124(1): 37-43, 2020 01.
Article in English | MEDLINE | ID: mdl-31806356

ABSTRACT

INTRODUCTION: Population Health Management initiatives are increasingly introduced, aiming to develop towards sustainable health and wellbeing systems. Yet, little is known about which strategies to implement during this development. This study provides insights into which strategies are used, why, and when, based on the experiences of nine Dutch Population Health Management initiatives. METHODS: The realist evaluation approach was used to gain an understanding of the relationships between context, mechanisms and outcomes when Population Health Management strategies were implemented. Data were retrieved from three interview rounds (n = 207) in 2014, 2016 and 2017. Data was clustered into guiding principles, underpinned with strategy-context-mechanism-outcome configurations. RESULTS: The Dutch initiatives experienced different developments, varying between immediate large-scale collaborations with eventual relapse, and incremental growth towards cross-sector collaboration. Eight guiding principles for development towards health and wellbeing systems were identified, focusing on: 1. Shared commitment for a Population Health Management-vision; 2. Mutual understanding and trust; 3. Accountability; 4. Aligning politics and policy; 5. Financial incentives; 6. A learning cycle based on a data-infrastructure; 7. Community input and involvement; and 8. Stakeholder representation and leadership. CONCLUSION: Development towards a sustainable health and wellbeing system is complex and time-consuming. Its success not only depends on the implementation of all eight guiding principles, but is also influenced by applying the right strategies at the right moment in the development.


Subject(s)
Health Care Reform , Health Policy , Leadership , Motivation , Population Health Management , Stakeholder Participation , Delivery of Health Care, Integrated , Humans , Interviews as Topic , Netherlands , Social Responsibility
11.
Expert Rev Clin Pharmacol ; 12(11): 1047-1057, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31575290

ABSTRACT

Introduction: The clinical use of tacrolimus is characterized by many side effects which include neurotoxicity. In contrast, tacrolimus has also shown to have neuroregenerative properties. On a molecular level, the mechanisms of action could provide us more insight into understanding the neurobiological effects. The aim of this article is to review current evidence regarding the use of tacrolimus in peripheral nerve injuries.Areas covered: Available data on tacrolimus' indications were summarized and molecular mechanisms were elucidated to possibly understand the conflicting neurotoxic and neuroregenerative effects. The potential clinical applications of tacrolimus, as immunosuppressant and enhancer of nerve regeneration in peripheral nerve injuries, are discussed. Finally, concepts of delivery are explored.Expert opinion: It is unclear what the exact neurobiological effects of tacrolimus are. Besides its known calcineurin inhibiting properties, the mechanism of action of tacrolimus is mediated by its binding to FK506-binding protein-52, resulting in a bimodal dose response. Experimental models found that tacrolimus administration is preferred up to three days prior to or within 10 days post-nerve reconstruction. Moreover, the indication for the use of tacrolimus has been expanding to fields of dermatology, ophthalmology, orthopedic surgery and rheumatology to improve outcomes after various indications.


Subject(s)
Nerve Regeneration/drug effects , Peripheral Nerve Injuries/drug therapy , Tacrolimus/administration & dosage , Animals , Calcineurin Inhibitors/administration & dosage , Calcineurin Inhibitors/adverse effects , Calcineurin Inhibitors/pharmacology , Drug Administration Schedule , Humans , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/pharmacology , Neurotoxicity Syndromes/etiology , Neurotoxicity Syndromes/physiopathology , Peripheral Nerve Injuries/physiopathology , Tacrolimus/adverse effects , Tacrolimus/pharmacology
12.
Clin Exp Immunol ; 197(3): 341-351, 2019 09.
Article in English | MEDLINE | ID: mdl-31059128

ABSTRACT

Cutaneous squamous cell carcinoma (cSCC) is a serious complication after organ transplantation and patients benefit from an early risk assessment. We hypothesized that functional differences in circulating T cells may represent risk factors for post-transplant cSCC development. Here, we analysed genome-wide DNA methylation of circulating T cells of kidney transplant recipients before the clinical onset of cSCC, to identify differences associated with post-transplant cSCC development. This analysis identified higher DNA methylation of SERPINB9, which is an intracellular inhibitor of granzyme B, a protein that induces apoptosis in target cells. High DNA methylation of SERPINB9 in circulating T cells was confirmed in a second patient cohort during recurrent cSCC, indicating that high SERPINB9 methylation represents a persistent risk factor for cSCC development. At the functional level, the inverse correlation between DNA methylation and messenger RNA expression present in non-cSCC patients was absent in the cSCC patients. Also, a significant difference in serpinB9 protein expression between cSCC patients and non-cSCC patients was observed. It was concluded that disturbed regulation of serpinB9 in circulating T cells represents a novel risk factor for post-transplant cSCC in kidney transplant recipients.


Subject(s)
Carcinoma, Squamous Cell/immunology , Down-Regulation/immunology , Kidney Transplantation/adverse effects , Serpins/immunology , Skin Neoplasms/immunology , T-Lymphocytes/immunology , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/etiology , Carcinoma, Squamous Cell/pathology , DNA Methylation/immunology , Female , Humans , Male , Middle Aged , Risk Factors , Skin Neoplasms/etiology , Skin Neoplasms/pathology , T-Lymphocytes/pathology
13.
BMC Health Serv Res ; 18(1): 285, 2018 04 13.
Article in English | MEDLINE | ID: mdl-29653537

ABSTRACT

BACKGROUND: Community engagement is increasingly seen as crucial to achieving high quality, efficient and collaborative care. However, organisations are still searching for the best and most effective ways to engage citizens in the shaping of health and care services. This review highlights the barriers and enablers for engaging communities in the planning, designing, governing, and/or delivering of health and care services on the macro or meso level. It provides policymakers and professionals with evidence-based guiding principles to implement their own effective community engagement (CE) strategies. METHODS: A Rapid Realist Review was conducted to investigate how interventions interact with contexts and mechanisms to influence the effectiveness of CE. A local reference panel, consisting of health and care professionals and experts, assisted in the development of the research questions and search strategy. The panel's input helped to refine the review's findings. A systematic search of the peer-reviewed literature was conducted. RESULTS: Eight action-oriented guiding principles were identified: Ensure staff provide supportive and facilitative leadership to citizens based on transparency; foster a safe and trusting environment enabling citizens to provide input; ensure citizens' early involvement; share decision-making and governance control with citizens; acknowledge and address citizens' experiences of power imbalances between citizens and professionals; invest in citizens who feel they lack the skills and confidence to engage; create quick and tangible wins; take into account both citizens' and organisations' motivations. CONCLUSIONS: An especially important thread throughout the CE literature is the influence of power imbalances and organisations' willingness, or not, to address such imbalances. The literature suggests that 'meaningful participation' of citizens can only be achieved if organisational processes are adapted to ensure that they are inclusive, accessible and supportive of citizens.


Subject(s)
Community Participation , Delivery of Health Care , Motivation , Decision Making , Humans , Quality of Health Care
14.
Neth J Med ; 76(1): 14-26, 2018 01.
Article in English | MEDLINE | ID: mdl-29380728

ABSTRACT

BACKGROUND: While conversion from cyclosporine to everolimus is well documented, conversion from tacrolimus has been poorly studied. In this randomised, controlled trial the safety and tolerability of switching from tacrolimus to everolimus with glucocorticoid withdrawal after living-donor kidney transplantation was studied. METHODS: A total of 194 patients were planned to be randomised 1:1 to either continue tacrolimus or to convert to everolimus at month 3 after transplantation. At randomisation, all patients received tacrolimus, mycophenolate mofetil and prednisolone. Everolimus was started in a dose of 1.5 mg twice daily, aiming for predose concentrations of 4-7 ng/ml. Prednisolone was gradually withdrawn in both groups. RESULTS: The trial was stopped prematurely after the inclusion of 60 patients. The interim analysis showed an unacceptably high rejection rate in the everolimus group as compared with the control group: 30.0% vs. 6.7% (95% CI: 0.047-0.420; p = 0.045). An additional 8 patients stopped everolimus because of toxicity. At the end of follow-up (month 12) only 12 (40%) patients assigned to everolimus were still on the study drug. CONCLUSIONS: Conversion from tacrolimus to everolimusbased immunosuppression with withdrawal of prednisolone three months after kidney transplantation results in an unacceptably high risk of acute rejection and causes considerable toxicity. Based on our findings, such a switch strategy cannot be recommended.


Subject(s)
Drug Substitution/adverse effects , Everolimus/administration & dosage , Glucocorticoids/administration & dosage , Graft Rejection/chemically induced , Immunosuppressive Agents/administration & dosage , Kidney Transplantation , Tacrolimus/administration & dosage , Adult , Aged , Female , Humans , Living Donors , Male , Middle Aged , Postoperative Period , Prospective Studies , Treatment Outcome
15.
Clin Exp Immunol ; 192(2): 224-232, 2018 05.
Article in English | MEDLINE | ID: mdl-29319177

ABSTRACT

We hypothesize that T cells such as interleukin (IL)-21+ B cell lymphoma 6 (BCL6)+ T follicular helper cells can regulate B cell-mediated immunity within the allograft during acute T cell-mediated rejection; this process may feed chronic allograft rejection in the long term. To investigate this mechanism, we determined the presence and activation status of organized T and B cells in so-called ectopic lymphoid structures (ELSs) in different types of acute renal allograft rejection. Biopsies showing the following primary diagnosis were included: acute/active antibody-mediated rejection, C4d+ (a/aABMR), acute T cell-mediated rejection grade I (aTCMRI) and acute T cell-mediated rejection grade II (aTCMRII). Paraffin sections were stained for T cells (CD3 and CD4), B cells (CD20), follicular dendritic cells (FDCs, CD23), activated B cells (CD79A), immunoglobulin (Ig)D, cell proliferation (Ki67) and double immunofluorescent stainings for IL-21 and BCL6 were performed. Infiltrates of T cells were detected in all biopsies. In aTCMRI, B cells formed aggregates surrounded by T cells. In these aggregates, FDCs, IgD and Ki67 were detected, suggesting the presence of ELSs. In contrast, a/aABMR and aTCMRII showed diffuse infiltrates of T and B cells but no FDCs and IgD. IL-21 was present in all biopsies. However, co-localization with BCL6 was observed mainly in aTCMRI biopsies. In conclusion, ELSs with an activated phenotype are found predominantly in aTCMRI where T cells co-localize with B cells. These findings suggest a direct pathway of B cell alloactivation at the graft site during T cell mediated rejection.


Subject(s)
B-Lymphocytes/immunology , Graft Rejection/immunology , Kidney Transplantation , T-Lymphocytes, Helper-Inducer/immunology , Tertiary Lymphoid Structures/immunology , Adult , Aged , Biopsy , Dendritic Cells, Follicular/immunology , Female , Humans , Interleukins/metabolism , Ki-67 Antigen/analysis , Kidney/pathology , Male , Middle Aged , Proto-Oncogene Proteins c-bcl-6/metabolism , Retrospective Studies , Transplantation, Homologous
16.
Am J Transplant ; 18(2): 341-350, 2018 02.
Article in English | MEDLINE | ID: mdl-28858434

ABSTRACT

Proinflammatory, cytotoxic CD4+ CD28null T cells can be substantially expanded in patients with end-stage renal disease. These cells have been associated with the risk for rejection, but their alloreactive potential is unknown. CD4+ CD28null T cells were stimulated with HLA-mismatched antigen presenting cells in the absence/presence of exogenous cytokines. Alloreactive potential was evaluated based on proliferation, degranulation, cytotoxicity, and cytokine production. Further, their suppressive capacity was assessed by measuring inhibition of proliferating alloreactive CD28+ T cells. CD4+ CD28null T cells contained alloreactive (CD137+ ) T cells but did not proliferate in response to allogeneic stimulation, unless interleukin (IL)-15 was added. However, they could proliferate on stimulation with cytomegalovirus antigen without exogenous cytokines. IL-15 increased the frequency of proliferating alloreactive CD4+ CD28null T cells to 30.5% without inducing CD28 expression (P < .05). After allogeneic stimulation together with IL-15 and IL-21, frequency of degranulating CD107a+ CD4+ CD28null T cells increased significantly from 0.6% to 5.8% (P < .001). Granzyme B and perforin positivity remained similar, but production of interferon-γ and tumor necrosis factor-α increased by the combination of IL-15 and IL-21 (P < .001 and P < .05, respectively). Finally, CD4+ CD28null T cells did not show significant suppression. Thus, CD4+ CD28null T cells represent a population with absent alloreactivity unless IL-15 is present.


Subject(s)
Antigen-Presenting Cells/immunology , CD28 Antigens/metabolism , CD4-Positive T-Lymphocytes/immunology , Interleukin-15/metabolism , Kidney Failure, Chronic/surgery , Lymphocyte Activation/immunology , T-Lymphocytes, Cytotoxic/immunology , Adult , Aged , CD4-Positive T-Lymphocytes/metabolism , Female , Follow-Up Studies , Humans , Interleukins/metabolism , Kidney Transplantation , Male , Middle Aged , Prognosis
17.
Clin Exp Immunol ; 191(3): 363-372, 2018 03.
Article in English | MEDLINE | ID: mdl-29027667

ABSTRACT

Blockade of the CD80/86-CD28 pathway by belatacept after kidney transplantation is associated with an increased risk of rejection compared with standard, calcineurin inhibitor (CNI)-based therapy. CD28- T cells, which express CD57, are not susceptible to belatacept treatment. High numbers of CD4+ CD57+ programmed death 1 (PD-1)- T cells pretransplantation have been associated with a higher chance of rejection, although conflicting data have been reported. To investigate the working mechanism behind this possible higher chance of rejection, we studied the expression of co-inhibitory molecules (CD223, CD244 and PD-1), proliferative capacity and cytotoxic potential of fluorescence activated cell sorted (FACS) CD4+ CD57+ PD-1- and CD8+ CD57+ PD-1- T cells, and their CD57- control populations, after alloantigen stimulation. The effect of belatacept on the cytotoxic capacity of pretransplantation peripheral blood mononuclear cells from 20 patients who received belatacept post-transplantation was also tested. Expression of co-inhibitory molecule CD223 increased by approximately 10-fold after allogeneic stimulation in all four T cell subsets. Proliferation and up-regulation of CD244 and PD-1 was observed for CD4+ CD57- PD-1- T cells after allogeneic stimulation, but no up-regulation of these markers occurred on CD8+ T cells or CD4+ CD57+ PD-1- T cells. However, CD4+ CD57+ PD-1- T cells and, to a lesser extent, CD8+ CD57+ PD-1- T cells displayed higher cytotoxicity as indicated by granzyme B expression. Belatacept inhibited the cytotoxic potential of CD4+ CD57+ PD-1- T cells (median of inhibition 31%, P < 0·01) and CD8+ CD57+ PD-1- T cells (median of inhibition 10%, P < 0·05). In conclusion, alloantigen-activated CD4+ CD57+ PD-1- T cells exhibited a less proliferative but more cytotoxic profile than their CD57- counterparts. Their cytotoxic capacity can be inhibited partly by belatacept and was not associated with development of rejection after kidney transplantation.


Subject(s)
Abatacept/therapeutic use , Graft Rejection/immunology , Immunosuppressive Agents/therapeutic use , Kidney Failure, Chronic/immunology , Kidney Transplantation , T-Lymphocytes, Cytotoxic/immunology , Adult , Aged , Antigens, CD/metabolism , CD57 Antigens/metabolism , Cell Proliferation , Cells, Cultured , Cytotoxicity, Immunologic , Female , Graft Rejection/drug therapy , Humans , Isoantigens/immunology , Kidney Failure, Chronic/therapy , Male , Middle Aged , Netherlands , Programmed Cell Death 1 Receptor/metabolism , Signaling Lymphocytic Activation Molecule Family/metabolism , Lymphocyte Activation Gene 3 Protein
18.
Ned Tijdschr Geneeskd ; 161: D849, 2017.
Article in Dutch | MEDLINE | ID: mdl-28443805

ABSTRACT

OBJECTIVE: To map initiatives in the Netherlands using a population-targeted approach to link prevention, care and welfare. DESIGN: Descriptive investigation, based on conversations and structured interviews. METHOD: We searched for initiatives in which providers in the areas of prevention, care and welfare together with health insurers and/or local authorities attempted to provide the 'triple aim': improving the health of the population and the quality of care, and managing costs. We found potential initiatives on the basis of interviews with key figures, project databases and congress programmes. We looked for additional information on websites and via contact persons to gather additional information to determine whether the initiative met the inclusion criteria. An initiative should link prevention, care and welfare with a minimum of three players actively pursuing a population-targeted goal through multiple interventions for a non-disease specific and district-transcending population. We described the goal, organisational structure, parties involved, activities and funding on the basis of interviews conducted in the period August-December 2015 with the managers of the initiatives included. RESULTS: We found 19 initiatives which met the criteria where there was experimentation with organisational forms, levels of participation, interventions and funding. It was noticeable that the interventions mostly concerned medical care. There was a lack of insight into the 'triple aim', mostly because data exchange between parties is generally difficult. CONCLUSION: There is an increasing number of initiatives that follow a population-targeted approach. Although the different parties strive to connect the three domains, they are still searching for an optimal collaboration, organisational form, data exchange and financing.


Subject(s)
Preventive Medicine/organization & administration , Public Health , Quality of Health Care , Humans , Netherlands
19.
Am J Transplant ; 17(10): 2659-2667, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28332287

ABSTRACT

Acute rejection is one of the major immunological determinants of kidney graft function and survival. Early biomarkers to predict rejection are lacking. Emerging evidence reveals a crucial role for the monocyte/macrophage lineage cells in the pathogenesis of rejection. We hypothesized that higher pretransplant numbers of proinflammatory CD16+ monocytes can predict rejection. The study cohort consisted of 104 kidney transplant recipients (58 with no rejection and 46 with biopsy-proven rejection) and 33 healthy persons. Posttransplant median follow-up time was 14.7 mo (interquartile range 0.3-34 mo). Pretransplantation blood samples were analyzed by flow cytometry for monocyte immunophenotypes. Groups were compared by Cox regression models for the occurrence of acute rejection. We documented a significantly increased absolute number of pretransplant CD16+ monocytes in patients who developed biopsy-proven rejection after transplantation compared with those with no rejection (hazard ratio [HR] 1.60, 95% CI 1.28-2.00, p < 0.001) and healthy persons (HR 1.47, 95% CI 1.18-1.82, p < 0.001). In parallel, significantly fewer absolute numbers of CD16- monocytes were observed at pretransplant time points in rejectors versus nonrejectors (HR 0.74, 95% CI 0.58-0.94, p < 0,014). A higher pretransplant number of CD16+ monocytes is significantly associated with a higher risk of acute rejection after kidney transplantation.


Subject(s)
Biomarkers/blood , Graft Rejection , Kidney Transplantation , Monocytes/immunology , Receptors, IgG/immunology , Adult , Case-Control Studies , Cohort Studies , Female , GPI-Linked Proteins/immunology , Humans , Immunophenotyping , Male , Middle Aged , Pilot Projects
20.
Ned Tijdschr Geneeskd ; 161: D701, 2017.
Article in Dutch | MEDLINE | ID: mdl-28294924

ABSTRACT

OBJECTIVE: Is the simple mean of the costs per diabetes patient a suitable tool with which to compare care groups? Do the total costs of care per diabetes patient really give the best insight into care group performance? DESIGN: Cross-sectional, multi-level study. METHOD: The 2009 insurance claims of 104,544 diabetes patients managed by care groups in the Netherlands were analysed. The data were obtained from Vektis care information centre. For each care group we determined the mean costs per patient of all the curative care and diabetes-specific hospital care using the simple mean method, then repeated it using the 'generalized linear mixed model'. We also calculated for which proportion the differences found could be attributed to the care groups themselves. RESULTS: The mean costs of the total curative care per patient were €3,092 - €6,546; there were no significant differences between care groups. The mixed model method resulted in less variation (€2,884 - €3,511), and there were a few significant differences. We found a similar result for diabetes-specific hospital care and the ranking position of the care groups proved to be dependent on the method used. The care group effect was limited, although it was greater in the diabetes-specific hospital costs than in the total costs of curative care (6.7% vs. 0.4%). CONCLUSION: The method used to benchmark care groups carries considerable weight. Simply stated, determining the mean costs of care (still often done) leads to an overestimation of the differences between care groups. The generalized linear mixed model is more accurate and yields better comparisons. However, the fact remains that 'total costs of care' is a faulty indicator since care groups have little impact on them. A more informative indicator is 'costs of diabetes-specific hospital care' as these costs are more influenced by care groups.

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