Healthcare professionals as change agents: Factors influencing bottom-up, personal initiatives on appropriate care, a qualitative study in the Netherlands.

INTRODUCTION: Healthcare organisations face multiple challenges, often conceptualised as appropriate care. It requires change on different levels: healthcare systems (macro), healthcare organisations (meso), and healthcare professionals (micro). This study focuses on bottom-up changes initiated by healthcare professionals. The aim is to investigate hindering and stimulating factors healthcare professionals experience. MATERIALS AND METHODS: The study used a qualitative design with purposive sampling of eight Dutch healthcare professionals who initiated changes. We conducted online interviews and used Atlas TI with a combination of open, axial, and selective coding for data analysis. RESULTS: The results indicate that professionals are often mission-driven when they initiate change, support from clients and peers may help them overcome barriers. Conversely, peers who feel threatened in their autonomy hinder initiatives of professionals, especially when their changes have financial consequences for their organization. CONCLUSION: Aligning and integrating macro- and micro-level initiatives is crucial to advancing the movement towards appropriate care and stimulating bottom-up initiatives of healthcare professionals. More research remained needed, in particular studies on the hindering or stimulating role of employers and healthcare professionals' representatives, and the adoption of the concept of appropriate care by patients.

Collaboration to combat COVID-19: policy responses and best practices in local integrated care settings.

PURPOSE: This illustrative case study describes and evaluates drivers of effective inter-organizational collaboration to mitigate the impact and spread of COVID-19 among homeless people in two cities in the Netherlands. The aims of this study are: (1) to explore the strategic and operational policy responses in two local integrated care settings at the start of the crisis, (2) to identify best policy practices and lessons learned. The authors interpret and evaluate the findings by combining insights from the population health management (PHM) and collaborative governance literature. DESIGN/METHODOLOGY/APPROACH: The authors describe and illustrate the experiences of two Dutch municipalities, Rotterdam and The Hague, in the early policy responses to sudden operational challenges around the impact of COVID-19 on homeless people as experienced by local decision-makers, medical doctors and clients. FINDINGS: The authors show that best policy practices revolve around (1) using data and risk stratification methods for identifying and targeting populations at-risk in local policy making, and (2) having an inter-organizational data sharing architecture in place ex ante. These two factors were clear prerequisites for tailor-made policy responses for newly-defined groups at risk with the existing and well-documented vulnerable population, and executing crisis-induced tasks efficiently. ORIGINALITY/VALUE: This paper is among the first to illustrate the potential of combining collaborative governance and PHM perspectives to identify key drivers of effective local governance responses to a healthcare crisis in an integrated care setting.

[Patient involvement during crises]. / Patiëntbetrokkenheid tijdens crisisbesluitvorming: Lessen voor de toekomst op basis van COVID-19.

Patient involvement is an important topic in health care. Client councils are one way through which patients are involved in decision-making. However, we know little about their role during crises, and what we can learn from these experiences. We argue that there was little patient involvement in the top-down and centralized decision-making during the COVID-19 crisis. Furthermore, many decisions were taken in interorganizational networks, where patient involvement is rare. Based on these findings, we argue that health care organizations and client councils should rethink what effective patient involvement looks like during crises and in interorganizational networks.

Activating anti-CD40 antibodies induce tumour invasion by cytotoxic T-lymphocytes and inhibition of tumour growth in experimental liver cancer.

The aim of this study was to investigate the effects of an activating anti-CD40 antibody (aCD40Ab) on leukocyte adhesion to tumour vessels, leukocyte migration and tumour growth in experimental liver cancer. Morris-Hepatoma was induced by subcapsular inoculation of tumour cells in the liver of ACI-rats. On day 7 and 8 after tumour cell injection, one group of the animals received aCD40Ab. On day 13 the tumour volume was measured and intravital microscopy was performed quantifying leukocyte adherence in the liver. Furthermore, immunohistological analyses were performed. aCD40Ab-Treated animals showed increased leukocyte-endothelium interaction, demonstrated substantially more T- and natural killer (NK) cells in the tumour and had a distinctly decreased tumour volume. Our results show that treatment with aCD40Ab stimulates endothelial leukocyte adhesion in tumour vessels and migration of CD4 cells/CD8 T-cells and NK cells into the tumour and inhibits tumour growth. Thus, the CD40/CD154 pathway is a worthwhile target for adjuvant immunotherapy.

Enhancement of leukocyte adhesion after percutaneous irradiation in rats with hepatocellular carcinoma.

AIM: To evaluate the effects of percutaneous radiation on leukocyte-endothelium interaction (LEI) in experimental hepatocellular carcinoma (HCC). METHODS: Twelve ACI rats underwent HCC-inoculation, six of which on day 12 received low-dose external radiation and six did not. After 12 h intravital microscopy was performed. RESULTS: LEI was significantly reduced in tumor tissue. However, irradiation of liver sinusoids and tumor tissue with 6 Gy led to a significant activation of leukocyte adhesion in the tumor with a marked increase of the proinflammatory cytokine TNF-alpha. CONCLUSION: The findings indicate that the immunological tumor-endothelial barrier can be overcome by external irradiation.

Expansion of endothelial surface by an increase of vessel diameter during tumor angiogenesis in experimental and hepatocellular and pancreatic cancer.

AIM: A low vessel density is a common feature of malignant tumors. We suggested that the expansion of vessel diameter might reconstitute the oxygen and nutritient's supply in this situation. The aim of the present study was to compare the number and diameter of blood vessels in pancreatic and liver carcinoma with normal tissue. METHODS: Tumor induction of pancreatic (DSL6A) or hepatocellular (Morris-hepatoma) carcinoma was performed in male Lewis (pancreatic cancer) and ACI (hepatoma) rats by an orthotopic inoculation of solid tumor fragments (pancreatic cancer) or tumor cells (hepatoma). Six weeks (pancreatic cancer) or 12 d (hepatoma) after tumor implantation, the tumor microvasculature as well as normal pancreatic or liver blood vessels were investigated by intravital microscopy. The number of perfused blood vessels in tumor and healthy tissue was assessed by computer-assisted image analysis. RESULTS: The vessel density in healthy pancreas (565+/-89 n/mm(2)) was significantly higher compared to pancreatic cancer (116+/-36 n/mm(2)) (P<0.001). Healthy liver showed also a significantly higher vessel density (689+/-36 n/mm(2)) compared to liver carcinoma (286+/-32 n/mm(2)) (P<0.01). The comparison of diameter frequency showed a significant increase of vessel diameter in both malignant tumors compared to normal tissue (P<0.05). CONCLUSION: The expansion of endothelial cells during tumor angiogenesis is accompanied to a large extent by an increase of vessel diameter rather than by formation of new blood vessels. This may be a possible adaptive mechanism by which experimental pancreatic and hepatocellular cancers expand their endothelial diffusion surface of endothelium to compensate for inadequate neoangiogenesis.

Effect of N-acetylcysteine on microcirculation of mucosa in rat ileum in a model of intestinal inflammation.

Oxygen radicals are formed by the endothelium and blood cells and have specific functions in various organs systems. On the level of the microcirculation, oxygen radicals take part in the regulation of the leukocyte-endothelial interaction. The involvement of oxygen radicals has previously been found in conditions such as sepsis, ischemia-reperfusion, and inflammation. Indomethacin is a clinically applied nonsteroidal antiphlogistic, and in previous studies in the rat, it has been found to induce an inflammatory reaction in the small intestine characterized by edema and reddening of the intestinal epithelium, ulceration, and dysregulation in the intestinal-epithelial barrier function. In the present study, we investigated the effect of N-acetylcysteine on erythrocyte velocity and the arteriolar diameter of the main arteriole in single villi, thus providing insight in the perfusion of the mucosa in indomethacin-induced intestinal inflammation. N-Acetylcysteine is known to inactivate superoxide and its precursors. Therefore, we used N-acetylcysteine to investigate whether superoxide and its precursors participate in the regulation of blood supply to single villi in this animal model. We found that indomethacin induced an increase in villous perfusion that was significantly reduced by N-acetylcysteine, indicating that superoxide and its precursors may participate in the regulation of blood supply to the mucosa in this animal model of intestinal inflammation.