The data was presented as part of a plenary that I gave at the 2021 ISPD virtual conference presentation on fetal therapy.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
ObjectiveTumour necrosis factor signalling via the receptor-interacting protein kinase 1 (RIPK1) pathway regulates colonic inflammation suggesting that RIPK1 inhibition may be a potential therapeutic target in ulcerative colitis (UC). This phase IIa, randomised, double-blind experimental medicine study investigated the safety, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of the RIPK1 inhibitor GSK2982772 in patients with active UC.DesignIn part A, prior to a protocol amendment, one patient was randomised to receive GSK2982772 60 mg twice daily for 42 days. After the amendment, patients were randomised 2:1 to receive GSK2982772 60 mg or placebo three times daily for 42 days. In part B, all patients switched to open-label GSK2982772 60 mg three times daily for 42 days. Safety, PK, PD biomarkers, histological disease activity, clinical efficacy and quality of life were assessed at days 43 and 85.ResultsThirty-six patients were randomised (n=12, placebo/open-label GSK2982772; n=24, GSK2982772/open-label GSK2982772). Most adverse events were mild, with headache reported the most frequently across groups (placebo/open-label GSK2982772, n=2 (17%); GSK2982772/open-label GSK2982772, n=8 (33%)). GSK2982772 was well distributed into colonic tissue, with generally higher concentrations in colonic biopsy samples versus plasma. No apparent differences between treatment groups were observed for PD, histological disease activity, clinical disease activity or quality-of-life measures. At screening, all patients had Mayo endoscopic scores of 2 or 3. At day 43, no patients in the placebo/open-label GSK2982772 group achieved Mayo endoscopic scores of 0 or 1 vs 3/24 (13%) for GSK2982772/open-label GSK2982772. At day 85, 1/9 (11%) achieved scores of 0 or one for placebo/open-label GSK2982772 vs 3/22 (14%) for GSK2982772/open-label GSK2982772.ConclusionGSK2982772 was generally well tolerated, with no treatment-related safety concerns identified. However, no significant differences in efficacy were observed between treatment groups, suggesting that GSK2982772 as monotherapy is not a promising treatment for patients with active UC.Trial registration numberNCT02903966.
Background While many studies address the clinical management of participants with uncomplicated urinary tract infection (uUTI), the emotional impact of uUTIs has been investigated less often. The aim of this qualitative study was to understand the emotional experience of women with uUTIs. Methods This was a qualitative, exploratory, in-depth interview-based study conducted among women in the United States (US) and Germany. Women aged ≥ 18 years with at least one uUTI treated with antibiotics in the past year were recruited through a patient community panel and physician referrals. Participants were recruited using purposive sampling to include an equal split of those with 1 or ≥ 2 antibiotics, and an equal split of those treated for a single or recurrent uUTIs (≥ 2 uUTIs in the past year). A structured telephone interview included questions about symptoms, diagnosis, treatment, and retreatment (if any). Each participant was queried about her emotions and the impact of the uUTI on life activities. Thematic analysis of responses was carried out to identify common themes. Results A total of 65 participants completed the interview, 40 (61.5%) from the US and 25 (38.5%) from Germany. Major themes that emerged from the analyses included (1) a wide range of negative emotions were experienced due to uUTI symptoms, interference with activities of daily life, and effects on relationships and sleep; (2) varied emotions and understanding related to uUTI treatment and management approaches; (3) treatment failure caused frustration, worry, and anger; and (4) the prospect of recurrent uUTIs provoked dread and helplessness. Conclusion Our research uncovered emotions of helplessness and dread experienced by women in the context of uUTI clinical treatment failure and recurrent uUTIs. Knowing patients’ perspectives on UTI management will help guide the development of patient education and improve shared decision-making.
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