Exploring co-dispensed drug use in patients on sevelamer or polystyrene sulfonate to identify potential novel binding interactions:a cross sectional in silico study: Potential novel binding interactions with resins

Background Sevelamer and polystyrene sulfonate are used for treating hyperphosphatemia and hyperkalaemia in chronic kidney disease patients. Because of their binding properties, these resins potentially bind other drugs in the gastrointestinal tract, thereby decreasing their bioavailability and clinical effectiveness. Aim The aim of this study was to explore co-dispensed drug use in patients on sevelamer or polystyrene sulfonate to identify potential novel binding interactions. Method In this in silico study, the 100 drugs most frequently co-dispensed with sevelamer/polystyrene sulfonate in the period 2000-2018 were extracted from the University Groningen IADB.nl database. Drugs dispensed to  2.0 were identified as potential interacting drug. For polystyrene sulfonate, drugs with a pKa (base) > 1.5 were identified as potential interacting drug. Results Of the top 100 drugs most frequently co-dispensed with sevelamer/polystyrene sulfonate, 22 and 27 potentially clinically relevant new interacting drugs were identified for sevelamer and polystyrene sulfonate respectively. Conclusion Several potentially relevant novel binding interactions for sevelamer and polystyrene sulfonate were identified based on dispensing data and assessment of chemical properties for which further interaction research is warranted

Dendritic Cell Migration to Skin-Draining Lymph Nodes Is Controlled by Dermatan Sulfate and Determines Adaptive Immunity Magnitude

Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease

Sialic acid-modified antigens impose tolerance via inhibition of T-cell proliferation and de novo induction of regulatory T cells

Sialic acids are negatively charged nine-carbon carboxylated monosaccharides that often cap glycans on glycosylated proteins and lipids. Because of their strategic location at the cell surface, sialic acids contribute to interactions that are critical for immune homeostasis via interactions with sialic acid-binding Ig-type lectins (siglecs). In particular, these interactions may be of importance in cases where sialic acids may be overexpressed, such as on certain pathogens and tumors. We now demonstrate that modification of antigens with sialic acids (Sia-antigens) regulates the generation of antigen-specific regulatory T (Treg) cells via dendritic cells (DCs). Additionally, DCs that take up Sia-antigen prevent formation of effector CD4+ and CD8+ T cells. Importantly, the regulatory properties endowed on DCs upon Sia-antigen uptake are antigen-specific: only T cells responsive to the sialylated antigen become tolerized. In vivo, injection of Sia-antigen–loaded DCs increased de novo Treg-cell numbers and dampened effector T-cell expansion and IFN-γ production. The dual tolerogenic features that Sia-antigen imposed on DCs are Siglec-E–mediated and maintained under inflammatory conditions. Moreover, loading DCs with Sia-antigens not only inhibited the function of in vitro–established Th1 and Th17 effector T cells but also significantly dampened ex vivo myelin-reactive T cells, present in the circulation of mice with experimental autoimmune encephalomyelitis. These data indicate that sialic acid-modified antigens instruct DCs in an antigen-specific tolerogenic programming, enhancing Treg cells and reducing the generation and propagation of inflammatory T cells. Our data suggest that sialylation of antigens provides an attractive way to induce antigen-specific immune tolerance

Change in antihypertensive drug prescribing after guideline implementation: a controlled before and after study

<p>Abstract</p> <p>Background</p> <p>Antihypertensive drug choices and treatment levels are not in accordance with the existing guidelines. We aimed to assess the impact of a guideline implementation intervention on antihypertensive drug prescribing.</p> <p>Methods</p> <p>In this controlled before and after study, the effects of a multifaceted (education, audit and feedback, local care pathway) quality programme was evaluated. The intervention was carried out in a health centre between 2002 and 2003. From each health care unit (n = 31), a doctor-nurse pair was trained to act as peer facilitators in the intervention.</p> <p>All antihypertensive drugs prescribed by 25 facilitator general practitioners (intervention GPs) and 53 control GPs were retrieved from the nationwide Prescription Register for three-month periods in 2001 and 2003. The proportions of patients receiving specific antihypertensive drugs and multiple antihypertensive drugs were measured before and after the intervention for three subgroups of hypertension patients: hypertension only, with coronary heart disease, and with diabetes.</p> <p>Results</p> <p>In all subgroups, the use of multiple concurrent medications increased. For intervention patients with hypertension only, the odds ratio (OR) was 1.12 (95% CI 0.99, 1.25; p = 0.06) and for controls 1.13 (1.05, 1.21; p = 0.002). We observed no statistically significant differences in the change in the prescribing of specific antihypertensive agents between the intervention and control groups. The use of agents acting on the renin-angiotensin-aldosterone system increased in all subgroups (hypertension only intervention patients OR 1.19 (1.06, 1.34; p = 0.004) and controls OR 1.24 (1.15, 1.34; p < 0.0001).</p> <p>Conclusions</p> <p>A multifaceted guideline implementation intervention does not necessarily lead to significant changes in prescribing performance. Rigorous planning of the interventions and quality projects and their evaluation are essential.</p

Whose Sense of Place? A Political Ecology of Amenity Development

Using a political ecology framework, this chapter examines the ways in which sense of place and amenity migration contribute to alternative residential development, which relies on uneven use of conservation subdivision features in the American West. Using case studies from Central Oregon, this chapter demonstrates how senses of place and developer decision-making are tied to wider political economic changes. It highlights the roles that amenity migrants and developers, two groups that are sometimes identical, play in landscape transformations that simultaneously draw on a particular sense of place and commodify landscapes in new ways

Guidelines and mindlines: why do clinical staff over-diagnose malaria in Tanzania? A qualitative study

BACKGROUND: Malaria over-diagnosis in Africa is widespread and costly both financially and in terms of morbidity and mortality from missed diagnoses. An understanding of the reasons behind malaria over-diagnosis is urgently needed to inform strategies for better targeting of antimalarials. METHODS: In an ethnographic study of clinical practice in two hospitals in Tanzania, 2,082 patient consultations with 34 clinicians were observed over a period of three months at each hospital. All clinicians were also interviewed individually as well as being observed during routine working activities with colleagues. Interviews with five tutors and 10 clinical officer students at a nearby clinical officer training college were subsequently conducted. RESULTS: Four, primarily social, spheres of influence on malaria over-diagnosis were identified. Firstly, the influence of initial training within a context where the importance of malaria is strongly promoted. Secondly, the influence of peers, conforming to perceived expectations from colleagues. Thirdly, pressure to conform with perceived patient preferences. Lastly, quality of diagnostic support, involving resource management, motivation and supervision. Rather than following national guidelines for the diagnosis of febrile illness, clinician behaviour appeared to follow 'mindlines': shared rationales constructed from these different spheres of influence. Three mindlines were identified in this setting: malaria is easier to diagnose than alternative diseases; malaria is a more acceptable diagnosis; and missing malaria is indefensible. These mindlines were apparent during the training stages as well as throughout clinical careers. CONCLUSION: Clinicians were found to follow mindlines as well as or rather than guidelines, which incorporated multiple social influences operating in the immediate and the wider context of decision making. Interventions to move mindlines closer to guidelines need to take the variety of social influences into account

Radiotherapeutic alternatives for previously irradiated recurrent gliomas

Re-irradiation for recurrent gliomas has been discussed controversially in the past. This was mainly due to only marginal palliation while being associated with a high risk for side effects using conventional radiotherapy