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2021 ◽  
pp. 1-10
Hiroyasu Yamamoto ◽  
Kiyoshi Nobori ◽  
Yoshimi Matsuda ◽  
Yasuhiro Hayashi ◽  
Takanori Hayasaki ◽  

<b><i>Introduction:</i></b> Erythropoiesis-stimulating agents (ESAs) are the current standard of care for anemia due to chronic kidney disease (CKD) in patients not undergoing dialysis. Molidustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, is being investigated as an alternative treatment for renal anemia. Molidustat was evaluated in five phase 3 studies, the molidustat once daily improves renal anemia by inducing erythropoietin (MIYABI) program. The present study investigated the safety and efficacy of molidustat in Japanese patients with renal anemia not undergoing dialysis and previously treated with ESAs. <b><i>Methods:</i></b> This was a 52-week, active-controlled, randomized (1:1), open-label, parallel-group, multicenter, phase 3 study in Japanese patients with anemia due to CKD (stages 3–5). Molidustat was initiated at 25 mg or 50 mg once daily according to previous ESA dose. The ESA darbepoetin alfa (darbepoetin) was initiated at a starting dose in accordance with the previous ESA dose and injected subcutaneously once every 2 or 4 weeks. Doses were regularly titrated to maintain hemoglobin (Hb) levels in the target range of 11.0–13.0 g/dL. The primary efficacy outcome was the mean Hb level and its change from baseline during the evaluation period (weeks 30–36). The safety outcomes included evaluation of all adverse events. <b><i>Results:</i></b> In total, 164 patients were randomized to receive molidustat (<i>n</i> = 82) or darbepoetin (<i>n</i> = 82). Baseline characteristics were well balanced. Mean (standard deviation) Hb levels at baseline were 11.31 (0.68) g/dL for molidustat and 11.27 (0.64) g/dL for darbepoetin. The mean (95% confidence interval [CI]) for mean Hb levels during the evaluation period for molidustat (11.67 [11.48–11.85] g/dL) and darbepoetin (11.53 [11.31–11.74] g/dL) was within the target range. Based on a noninferiority margin of 1.0 g/dL, molidustat was noninferior to darbepoetin regarding the change in mean Hb level during the evaluation period from baseline, with a least squares mean (95% CI) difference (molidustat-darbepoetin) of 0.13 (−0.15, 0.40) g/dL. The proportion of patients who reported at least 1 treatment-emergent adverse event (TEAE) was 92.7% for molidustat and 96.3% for darbepoetin. TEAEs leading to death were reported in 2 patients (2.4%) in the molidustat group and none in the darbepoetin group; serious TEAEs were reported in 32.9% and 26.8% of patients, respectively. <b><i>Discussion/Conclusion:</i></b> Molidustat was noninferior to darbepoetin and maintained Hb levels in the prespecified target range in patients with renal anemia not undergoing dialysis and previously treated with ESA. Molidustat was well tolerated, and no new safety signal was observed.

Daniel Serrano ◽  
Lauren Podger ◽  
Gisoo Barnes ◽  
James Song ◽  
Boxiong Tang

AbstractTo demonstrate the measurement properties of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Hepatocellular Carcinoma 18-question module (EORTC QLQ-HCC18) within a previously treated, unresectable hepatocellular carcinoma (HCC) clinical trial population that was distinct from the published QLQ-HCC18 validation population. Analyses were conducted using data from BGB-A317-208, an open label, international, clinical trial assessing efficacy and safety of the monoclonal antibody tislelizumab in adult HCC patients. The EORTC Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and QLQ-HCC18 instruments were assessed at baseline and weeks 3 and 9 follow-up visits. Per US Food and Drug Administration guidance, psychometric validation of the QLQ-HCC18 included reliability (internal consistency and test–retest), construct validity (convergent and discriminant validity and known-groups validity), ability to detect change, and meaningful within-patient change (MWPC). Known-groups validity and MWPC analyses were also stratified on several pre-defined subgroups. A total of 248 patients were included. Only the QLQ-HCC18 fatigue, nutrition, and index domains demonstrated acceptable internal consistency; acceptable test–retest reliability was found for fatigue, body image, nutrition, pain, sexual interest, and index domains. The QLQ-HCC18 fatigue domain achieved the pre-specified criterion defining acceptable convergent and discriminant validity for 13 of 16 correlations, whereas the index domain achieved the pre-specified criterion for 14 of 16 correlations. Clear differentiation of the QLQ-HCC18 change scores between improvement and maintenance anchor groups were observed for body image, fatigue, pain, and index domains, whereas differentiation between deterioration and maintenance anchor groups were observed for fever and fatigue domains. MWPC point estimates defining improvement for the QLQ-HCC18 fatigue and index domains were −7.18 and −4.07, respectively; MWPC point estimates defining deterioration were 5.34 and 3.16, respectively. The EORTC QLQ-HCC18 fatigue and index domains consistently demonstrated robust psychometric properties, supporting the use of these domains as suitable patient-reported endpoints within a previously treated, unresectable HCC patient population.

2021 ◽  
Kindu Alem

Abstract Background: The rate of multidrug resistant tuberculosis is increasing at an alarming rate throughout the world. It is becoming an emerging public health problem in East Africa. Prevalence of MDR-TB among TB positive individuals in the region has not been synthesized. Determining the pooled prevalence of MDR-TB among newly diagnosed and previously treated TB cases in East Africa is the main objective of this review.Methods: In this systematic review and meta-analysis, the researcher searched six electronic databases: Google scholar, PubMed, EMBASE, Scopus, Science direct and Web of Science. Funnel plot symmetry visualization confirmed by Egger’s regression asymmetry test and Begg rank correlation methods was used to assess publication bias. The pooled prevalence estimate was calculated using Der Simonian and Laird’s random Effects model. A total of 16 articles published in East Africa from 2007 and 2019 were included in this study. STATA software (version 14, Texas, USA) was used for analysis. Results: Out of 1025 articles identified citations, a total of 16 articles published in East Africa from 2007 and 2019 were included in this meta-analysis. The pooled prevalence of MDR-TB among newly diagnosed TB cases and previously treated TB patients to be 4% (95%CI=2-5%) and 21% (95%CI: 14-28%), respectively. Living conditions, lifestyles (smoking, alcohol use, and drug abuse), previous medical history, diabetes history and HIV infection risk factors contribute to higher prevalence of MDR-TB in East Africa.Conclusion: An early diagnosis of tuberculosis and rapid detection of drug resistant Mycobacterium tuberculosis is a serious concern to identify patients who are not responding to the standard treatment and to avoid spreading of resistant strains. It is also very essential to strengthen tuberculosis control and improved monitoring of chemotherapy.

ESMO Open ◽  
2021 ◽  
Vol 6 (5) ◽  
pp. 100249
J.H. Kim ◽  
S.H. Kim ◽  
M.K. Jeon ◽  
J.E. Kim ◽  
K.H. Kim ◽  

2021 ◽  
Thomas Metayer ◽  
François Lechanoine ◽  
Nassim Bougaci ◽  
Emmanuel de Schlichting ◽  
Laura Terrier ◽  

2021 ◽  
Vol 21 ◽  
pp. S318
John C. Byrd ◽  
Peter Hillmen ◽  
Paolo Ghia ◽  
Arnon P. Kater ◽  
Asher Chanan-Khan ◽  

2021 ◽  
Vol 21 ◽  
pp. S315-S316
Catherine C. Coombs ◽  
John M. Pagel ◽  
Nirav N. Shah ◽  
Nicole Lamanna ◽  
Ewa Lech-Maranda ◽  

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