32 research outputs found
Fluticasone furoate nasal spray: Profile of an enhanced-affinity corticosteroid in treatment of seasonal allergic rhinitis
Of the classes of pharmacotherapy for seasonal allergic rhinitis, intranasal corticosteroids are the preferred treatment and are recommended in practice guidelines as first-line pharmacotherapy for rhinitis with prominent nasal congestion. The enhanced-affinity intranasal corticosteroid fluticasone furoate nasal spray (GW685698X), is one of the newest additions to the armamentarium for allergic rhinitis. This review summarizes the preclinical and clinical data on fluticasone furoate nasal spray and discusses its place in pharmacotherapy for seasonal allergic rhinitis. Important attributes of fluticasone furoate in seasonal allergic rhinitis include low systemic bioavailability (<0.5%), onset of symptom relief as early as eight hours after initiation of treatment, 24-hour symptom relief with once-daily dosing, comprehensive coverage of both nasal and ocular symptoms, safety and tolerability with daily use, and availability in a side-actuated device that makes medication delivery simple and consistent. With these attributes, fluticasone furoate nasal spray has the potential to enhance patient satisfaction and compliance and reduce the need for polypharmacy in the management of seasonal allergic rhinitis
In Vivo, Multimodal Imaging of B Cell Distribution and Response to Antibody Immunotherapy in Mice
BACKGROUND: B cell depletion immunotherapy has been successfully employed to treat non-Hodgkin's lymphoma. In recent years, increasing attention has been directed towards also using B-cell depletion therapy as a treatment option in autoimmune disorders. However, it appears that the further development of these approaches will depend on a methodology to determine the relation of B-cell depletion to clinical response and how individual patients should be dosed. Thus far, patients have generally been followed by quantification of peripheral blood B cells, but it is not apparent that this measurement accurately reflects systemic B cell dynamics. METHODOLOGY/PRINCIPAL FINDINGS: Cellular imaging of the targeted population in vivo may provide significant insight towards effective therapy and a greater understanding of underlying disease mechanics. Superparamagnetic iron oxide (SPIO) nanoparticles in concert with near infrared (NIR) fluorescent dyes were used to label and track primary C57BL/6 B cells. Following antibody mediated B cell depletion (anti-CD79), NIR-only labeled cells were expeditiously cleared from the circulation and spleen. Interestingly, B cells labeled with both SPIO and NIR were not depleted in the spleen. CONCLUSIONS/SIGNIFICANCE: Whole body fluorescent tracking of B cells enabled noninvasive, longitudinal imaging of both the distribution and subsequent depletion of B lymphocytes in the spleen. Quantification of depletion revealed a greater than 40% decrease in splenic fluorescent signal-to-background ratio in antibody treated versus control mice. These data suggest that in vivo imaging can be used to follow B cell dynamics, but that the labeling method will need to be carefully chosen. SPIO labeling for tracking purposes, generally thought to be benign, appears to interfere with B cell functions and requires further examination
Safety of procuring research tissue during a clinically indicated kidney biopsy from patients with lupus: data from the Accelerating Medicines Partnership RA/SLE Network
Objectives In lupus nephritis the pathological diagnosis from tissue retrieved during kidney biopsy drives treatment and management. Despite recent approval of new drugs, complete remission rates remain well under aspirational levels, necessitating identification of new therapeutic targets by greater dissection of the pathways to tissue inflammation and injury. This study assessed the safety of kidney biopsies in patients with SLE enrolled in the Accelerating Medicines Partnership, a consortium formed to molecularly deconstruct nephritis.Methods 475 patients with SLE across 15 clinical sites in the USA consented to obtain tissue for research purposes during a clinically indicated kidney biopsy. Adverse events (AEs) were documented for 30 days following the procedure and were determined to be related or unrelated by all site investigators. Serious AEs were defined according to the National Institutes of Health reporting guidelines.Results 34 patients (7.2%) experienced a procedure-related AE: 30 with haematoma, 2 with jets, 1 with pain and 1 with an arteriovenous fistula. Eighteen (3.8%) experienced a serious AE requiring hospitalisation; four patients (0.8%) required a blood transfusion related to the kidney biopsy. At one site where the number of cores retrieved during the biopsy was recorded, the mean was 3.4 for those who experienced a related AE (n=9) and 3.07 for those who did not experience any AE (n=140). All related AEs resolved.Conclusions Procurement of research tissue should be considered feasible, accompanied by a complication risk likely no greater than that incurred for standard clinical purposes. In the quest for targeted treatments personalised based on molecular findings, enhanced diagnostics beyond histology will likely be required
UK prescribing practices as proxy markers of unmet need in allergic rhinitis:A retrospective observational study
Little data on UK prescribing patterns and treatment effectiveness for allergic rhinitis (AR) are available. We quantified unmet pharmacologic needs in AR by assessing AR treatment effectiveness based on the prescribing behaviour of UK general practitioners (GP) during two consecutive pollen seasons (2009 and 2010). We conducted a retrospective observational study with the data from the Optimum Patient Care Research Database. We assessed diagnoses and prescription data for patients with a recorded diagnosis of rhinitis who took rhinitis medication during the study period. We assessed the data from 25,069 patients in 2009 and 22,381 patients in 2010. Monotherapy was the initial prescription of the season for 67% of patients with seasonal AR (SAR) and 77% of patients with nonseasonal upper airways disease (NSUAD), for both years. Initial oral antihistamine (OAH) or intranasal corticosteroid (INS) monotherapy proved insufficient for 420% of SAR and 437% of NSUAD patients. Multiple therapy was the initial prescription for 33% of SAR and 23% of NSUAD in both years, rising to 45% and 450% by season end, respectively. For NSUAD, dual-therapy prescriptions doubled and triple-therapy prescriptions almost tripled during both seasons. Many patients revisited their GP regardless of initial prescription. Initial OAH or INS monotherapy provides insufficient symptom control for many AR patients. GPs often prescribe multiple therapies at the start of the season, with co-prescription becoming more common as the season progresses. However, patients prescribed multiple therapies frequently revisit their GP, presumably to adjust treatment. These data suggest the need for more effective AR treatment and management strategies
Alkaptonuria
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