| 1. |
- Sokka, T., et al.
(author)
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Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST-RA database
- 2009
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 68:11, s. 1666-1672
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Journal article (peer-reviewed)abstract
- Objective: To analyse associations between the clinical status of patients with rheumatoid arthritis ( RA) and the gross domestic product (GDP) of their resident country. Methods: The Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) cohort includes clinical and questionnaire data from 6004 patients who were seen in usual care at 70 rheumatology clinics in 25 countries as of April 2008, including 18 European countries. Demographic variables, clinical characteristics, RA disease activity measures, including the disease activity score in 28 joints (DAS28), and treatment-related variables were analysed according to GDP per capita, including 14 "high GDP'' countries with GDP per capita greater than US$ 24 000 and 11 "low GDP'' countries with GDP per capita less than US$ 11 000. Results: Disease activity DAS28 ranged between 3.1 and 6.0 among the 25 countries and was significantly associated with GDP (r = -0.78, 95% CI -0.56 to -0.90, r(2) = 61%). Disease activity levels differed substantially between "high GDP'' and "low GDP'' countries at much greater levels than according to whether patients were currently taking or not taking methotrexate, prednisone and/or biological agents. Conclusions: The clinical status of patients with RA was correlated significantly with GDP among 25 mostly European countries according to all disease measures, associated only modestly with the current use of antirheumatic medications. The burden of arthritis appears substantially greater in "low GDP'' than in "high GDP'' countries. These findings may alert healthcare professionals and designers of health policy towards improving the clinical status of patients with RA in all countries.
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| 2. |
- Aslanis, Vassilios, et al.
(author)
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Safety and pharmacokinetics of GB1211, an oral galectin-3 inhibitor : a single- and multiple-dose first-in-human study in healthy participants
- 2023
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In: Cancer Chemotherapy and Pharmacology. - : Springer Science and Business Media LLC. - 0344-5704 .- 1432-0843. ; 91:3, s. 267-280
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Journal article (peer-reviewed)abstract
- PURPOSE: Galectin-3, a β-galactoside-binding lectin, plays a key role in several cellular pathways involved in chronic inflammation, heart disease and cancer. GB1211 is an orally bioavailable galectin-3 inhibitor, developed to be systemically active. We report safety and pharmacokinetics (PK) of GB1211 in healthy participants.METHODS: This phase 1, double-blind, placebo-controlled, first-in-human study (NCT03809052) included a single ascending-dose phase (with a food-effect cohort) where participants across seven sequential cohorts were randomized 3:1 to receive oral GB1211 (5, 20, 50, 100, 200 or 400 mg) or placebo. In the multiple ascending-dose phase, participants received 50 or 100 mg GB1211 or placebo twice daily for 10 days. All doses were administered in the fasted state except in the food-effect cohort where doses were given 30 min after a high-fat meal.RESULTS: All 78 participants received at least one GB1211 dose (n = 58) or placebo (n = 20) and completed the study. No safety concerns were identified. Following single and multiple oral doses under fasted conditions, maximum GB1211 plasma concentrations were reached at 1.75-4 h (median) post-dose; mean half-life was 11-16 h. There was a ~ twofold GB1211 accumulation in plasma with multiple dosing, with steady-state reached within 3 days; 30% of the administered dose was excreted in urine as unchanged drug. Absorption in the fed state was delayed by 2 h but systemic exposure was unaffected.CONCLUSION: GB1211 was well tolerated, rapidly absorbed, and displayed favorable PK, indicating a potential to treat multiple disease types. These findings support further clinical development of GB1211.CLINICAL TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov (identifier: NCT03809052).
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| 3. |
- MacLennan, Steven, et al.
(author)
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Systematic Review of Oncological Outcomes Following Surgical Management of Localised Renal Cancer
- 2012
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In: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 61:5, s. 972-993
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Research review (peer-reviewed)abstract
- Context: Renal cell carcinoma (RCC) accounts for 2-3% of adult malignancies. There remain uncertainties over the oncological outcomes for the surgical management of localised RCC. Objective: Systematically review relevant literature comparing oncological outcomes of surgical management of localised RCC (T1-2N0M0). Evidence acquisition: Relevant databases including Medline, Embase, and the Cochrane Library were searched up to October 2010, and an updated scoping search was performed up to January 2012. Randomised controlled trials (RCTs) or quasi-RCTs, prospective observational studies with controls, retrospective matched-pair studies, and comparative studies from well-defined registries/databases were included. The main outcomes were overall survival, cancer-specific survival, recurrence, and metastases. The Cochrane risk of bias tool was used to assess RCTs, and an extended version was used to assess nonrandomised studies (NRSs). The quality of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Evidence synthesis: A total of 4580 abstracts and 389 full-text articles were assessed. Thirty-four studies met the inclusion criteria (6 RCTs and 28 NRSs). Meta-analyses were planned but were deemed inappropriate due to data heterogeneity. There were high risks of bias and low-quality evidence across the evidence base. Open radical nephrectomy and open partial nephrectomy showed similar cancer-specific and overall survival, but when both open and laparoscopic approaches are considered together, the evidence showed improved survival for partial nephrectomy for tumours <= 4 cm. The overall evidence suggests either equivalent or better survival with partial nephrectomy. Laparoscopic radical nephrectomy offered equivalent survival to open radical nephrectomy, and all laparoscopic approaches achieved equivalent survival. Open and laparoscopic partial nephrectomy achieved equivalent survival. The issue of ipsilateral adrenalectomy or complete lymph node dissection with radical nephrectomy or partial nephrectomy remains unresolved. Conclusions: The evidence base suggests localised RCCs are best managed by nephron-sparing surgery where technically feasible. However, the current evidence base has significant limitations due to studies of low methodological quality marked by high risks of bias. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved.
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| 4. |
- MacLennan, Steven, et al.
(author)
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Systematic review of perioperative and quality-of-life outcomes following surgical management of localised renal cancer
- 2012
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In: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 62:6, s. 1097-1117
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Research review (peer-reviewed)abstract
- Context: For the treatment of localised renal cell carcinoma (RCC), uncertainties remain over the perioperative and quality-of-life (QoL) outcomes for the many different surgical techniques and approaches of nephrectomy. Controversy also remains on whether newer minimally invasive nephron-sparing interventions offer better QoL and perioperative outcomes, and whether adrenalectomy and lymphadenectomy should be performed simultaneously with nephrectomy. These non-oncological outcomes are important because they may have a considerable impact on localised RCC treatment decision making.Objective: To review systematically all the relevant published literature comparing perioperative and QoL outcomes of surgical management of localised RCC (T1-2N0M0).Evidence acquisition: Relevant databases including Medline, Embase, and the Cochrane Library were searched up to January 2012. Randomised controlled trials (RCTs) or quasi-randomised controlled trials, prospective observational studies with controls, retrospective matched-pair studies, and comparative studies from well-defined registries/databases were included. The outcome measures were QoL, analgesic requirement, length of hospital stay, time to normal activity level, surgical morbidity and complications, ischaemia time, renal function, blood loss, length of operation, need for blood transfusion, and perioperative mortality. The Cochrane risk of bias tool was used to assess RCTs, and an extended version was used to assess nonrandomised studies (NRSs). The quality of evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluation.Evidence synthesis: A total of 4580 abstracts and 380 full-text articles were assessed, and 29 studies met the inclusion criteria (7 RCTs and 22 NRSs). There were high risks of bias and low-quality evidence for studies meeting the inclusion criteria. There is good evidence indicating that partial nephrectomy results in better preservation of renal function and better QoL outcomes than radical nephrectomy regardless of technique or approach. Regarding radical nephrectomy, the laparoscopic approach has better perioperative outcomes than the open approach, and there is no evidence of a difference between the transperitoneal and retroperitoneal approaches. Alternatives to standard laparoscopic radical nephrectomy (LRN) such as hand-assisted, robot-assisted, or single-port techniques appear to have similar perioperative outcomes. There is no good evidence to suggest that minimally invasive procedures such as cryotherapy or radiofrequency ablation have superior perioperative or QoL outcomes to nephrectomy. Regarding concomitant lymphadenectomy during nephrectomy, there were low event rates for complications, and no definitive difference was observed. There was no evidence to base statements about concomitant ipsilateral adrenalectomy during nephrectomy.Conclusions: Partial nephrectomy results in significantly better preservation of renal function over radical nephrectomy. For tumours where partial nephrectomy is not technically feasible, there is no evidence that alternative procedures or techniques are better than LRN in terms of perioperative or QoL outcomes. In making treatment decisions, perioperative and QoL outcomes should be considered in conjunction with oncological outcomes. Overall, there was a paucity of data regarding QoL outcomes, and when reported, both QoL and perioperative outcomes were inconsistently defined, measured, or reported. The current evidence base has major limitations due to studies of low methodological quality marked by high risks of bias.(C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved.
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