Case management in primary care for frequent users of healthcare services with chronic diseases and complex care needs: an implementation and realist evaluation protocol.

INTRODUCTION: Significant evidence in the literature supports case management (CM) as an effective intervention to improve care for patients with complex healthcare needs. However, there is still little evidence about the facilitators and barriers to CM implementation in primary care setting. The three specific objectives of this study are to: (1) identify the facilitators and barriers of CM implementation in primary care clinics across Canada; (2) explain and understand the relationships between the actors, contextual factors, mechanisms and outcomes of the CM intervention; (3) identify the next steps towards CM spread in primary care across Canada. METHODS AND ANALYSIS: We will conduct a multiple-case embedded mixed methods study. CM will be implemented in 10 primary care clinics in five Canadian provinces. Three different units of analysis will be embedded to obtain an in-depth understanding of each case: the healthcare system (macro level), the CM intervention in the clinics (meso level) and the individual/patient (micro level). For each objective, the following strategy will be performed: (1) an implementation analysis, (2) a realist evaluation and (3) consensus building among stakeholders using the Technique for Research of Information by Animation of a Group of Experts method. ETHICS AND DISSEMINATION: This study, which received ethics approval, will provide innovative knowledge about facilitators and barriers to implementation of CM in different primary care jurisdictions and will explain how and why different mechanisms operate in different contexts to generate different outcomes among frequent users. Consensual and prioritised statements about next steps for spread of CM in primary care from the perspectives of all stakeholders will be provided. Our results will offer context-sensitive explanations that can better inform local practices and policies and contribute to improve the health of patients with complex healthcare needs who frequently use healthcare services. Ultimately, this will increase the performance of healthcare systems and specifically mitigate ineffective use and costs.

Lactoferrin against Staphylococcus aureus Mastitis. Lactoferrin alone or in combination with penicillin G on bovine polymorphonuclear function and mammary epithelial cells colonisation by Staphylococcus aureus.

Antibiotics should combine good antibacterial activity and the capacity to work in association with the host defence system. In this study, we have investigated the effects of bovine lactoferrin alone or in combination with penicillin G on the phagocytic activity of bovine polymorphonuclear leukocytes against Staphylococcus aureus. We have shown that susceptibility of S. aureus to phagocytosis was decreased in the presence of penicillin in the medium. In a kinetic study, lactoferrin alone did not affect phagocytosis but, when used with penicillin, it reversed the negative effect of this antibiotic on phagocytosis. In addition, in an epithelial invasion assay, lactoferrin alone or in combination with penicillin reduced the invasion of mammary epithelial cells in culture by S. aureus. Lactating female CD-1 mice were infected by intra-mammary delivery of a virulent penicillin-susceptible S. aureus strain and were then randomly assigned to treatments according to a 2 x 2 factorial design. In this mouse mastitis model, 2 days of systemic treatments with lactoferrin and/or penicillin did not lead to a total clearance of infection by S. aureus, but bacterial number was significantly reduced by treatments with lactoferrin or penicillin. These data suggest that bovine lactoferrin, alone or in combination with penicillin G, enhances S. aureus susceptibility to immuno-defense mechanisms, which can be beneficial in the treatment of S. aureus infections.

Ultrastructural and cytochemical study of cell wall modification by lactoferrin, lactoferricin and penicillin G against Staphylococcus aureus.

To investigate the effect of lactoferrin or lactoferricin with or without penicillin G, light and transmission electron microscopy were performed on thin sections of two Staphylococcus aureus strains. Lactoferrin affected the ultrastructure of S. aureus and groups of undivided cells were observed after lactoferrin treatment with or without penicillin G. These results suggest that lactoferrin can affect staphylococcal cell separation and therefore prevent dissemination of daughter cells from spreading infection. After treatment with lactoferrin, S. aureus cells were less covered (P<0.05) with wheatgerm agglutinin labelled with gold, thus suggesting that lactoferrin affected the synthesis of peptidoglycan and/or the binding to N-acetyl-beta-D-glucosamine. Lactoferricin with or without penicillin G induced the lysis of many bacteria, formation of mesosomal structures and modifications of cell wall. Lactating female CD-1 mice were infected by intramammary delivery of a penicillin-resistant S. aureus strain and were then randomly assigned to treatments according to a 2 x 2 factorial design. Electron microscopy examination showed that 2 days of systemic treatments with lactoferrin affected the morphology and aggregation of S. aureus. In conclusion, lactoferrin and lactoferricin affect S. aureus morphology which may facilitate its killing by penicillin G.