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Liu, Hong, Li Ma, Xu Wang, Xinzhong Chang, Qi Yu, Qingfeng Huang, Chunfang Hao et al. "Abstract P1-12-11: Real-world incidence and management of diarrhea secondary to pyrotinib in patients with HER-2 positive breast cancer". Cancer Research 83, n.º 5_Supplement (1 de março de 2023): P1–12–11—P1–12–11. http://dx.doi.org/10.1158/1538-7445.sabcs22-p1-12-11.

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Abstract Objective: Pyrotinib, an oral irreversible pan-HER receptor tyrosine kinase inhibitor, showed promising efficacy and manageable safety profiles in the treatment of HER-2 positive breast cancer. Diarrhea is the most common adverse event associated with pyrotinib. This study aimed to evaluate the incidence and management of diarrhea secondary to pyrotinib in Chinese patients with HER-2 positive breast cancer. Methods: In this prospective real-world study, consecutive patients aged over 18 with HER-2 positive breast cancer and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2 who planned to receive pyrotinib-based regimens for at least 21 days were included. Pyrotinib-treated patients and those with preexisting gastrointestinal conditions were excluded. There were no planned management strategy or primary prophylaxis for diarrhea, while loperamide, montmorillonite powder or Golden Bifid (a live combined Bifidobacterium, Lactobacillus and Streptococcus Thermophilus tablet) were recommended. Treatment was given in accordance with routine clinical practice by investigators. For patients developed grade 3 or higher diarrhea, pyrotinib was suspended until the diarrhea improving to grade 1 or less, and secondary prophylaxis (such as loperamide, loperamide plus montmorillonite powder, or loperamide plus Golden Bifid) was administrated before pyrotinib resumption. The baseline characteristics of patients and details of diarrhea (onset time, duration, severity according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.03, treatment and prognosis) were collected. Results: Between August, 2020 and April, 2022, a total of 107 eligible patients were included, with a median age of 54 (range: 25-81) years old. Most patients (93.5%) had an ECOG PS of 0-1, and 51 patients (47.7%) were hormone receptor positive. A total of 46 patients (43.0%) received pyrotinib in the early stage and 61 (57.0%) in the advanced stage. Sixty-nine cases (64.5%) used pyrotinib-containing combination therapy (including 40 combined with capecitabine, 13 combined with trastuzumab, and 16 combined with other regimens), and 38 (35.5%) received pyrotinib alone. Ninety-eight cases (91.6%) reported diarrhea of any grade. Grade 1, 2 and 3 diarrhea occurred in 78 (72.9%), 9 (8.4%) and 11 (10.3%) patients, respectively. The median time to first onset of diarrhea of any grade was 2.5 (1-12) days, and the duration of first onset was 4 (1-24) days. The cumulative duration of diarrhea was 10 (1-60) days. Sixty-four, two, thirty, two patients used loperamide alone, montmorillonite powder alone, loperamide plus montmorillonite powder and loperamide plus Golden Bifid for the treatment of diarrhea, respectively. Eleven (10.3%) and seven (6.5%) patients experienced pyrotinib dose reduction and pyrotinib discontinuation. For 11 patients suffered grade 3 diarrhea, the median time to first onset of grade 3 diarrhea was 9 (4-14) days. Two, four and five patients administrated loperamide, loperamide plus Golden Bifid and loperamide plus montmorillonite powder as their secondary prophylaxis. Ten of eleven had grade 1 or 2 diarrhea after secondary prophylaxis, while one patient still suffered grade 3 diarrhea. All of them (11/11) held the pyrotinib dose. The incidence rate of constipation of all patients was 3.7%, which did not increase after treatment or secondary prophylaxis for diarrhea. Conclusion: In this study, the majority of patients developed pyrotinib associated diarrhea, and most of them were grade 1. About 10% patients reported grade 3 diarrhea, which can be managed by loperamide-based treatment and secondary prophylaxis. Table 1. Baseline characteristics of patients ECOG PS: Eastern Cooperative Oncology Group performance status; HER-2: human epidermal growth factor receptor 2. Table 2. Summary of patients developed diarrhea Table 3. Summary of patients developed grade 3 diarrhea Citation Format: Hong Liu, Li Ma, Xu Wang, Xinzhong Chang, Qi Yu, Qingfeng Huang, Chunfang Hao, Jun Liu, Jing Zhao, Shufen Li, Zhongsheng Tong, Yehui Shi, Ning Lu, Weipeng Zhao, Tong Wang, Xuchen Cao, Chen Wang, Juntian Liu, Ying Zhao, Lina Zhang, Baoliang Guo, Xin Wang, Xu Di, Chunhui Gao, Zongzhan Liu, Shuo Sun, Linwei Li. Real-world incidence and management of diarrhea secondary to pyrotinib in patients with HER-2 positive breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-12-11.
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Aletaha, D., R. Westhovens, C. Gaujoux-Viala, G. Adami, A. Matsumoto, P. Bird, O. Messina et al. "THU0188 EFFICACY OF FILGOTINIB IN PATIENTS WITH RHEUMATOID ARTHRITIS WITH POOR PROGNOSTIC FACTORS: POST HOC ANALYSIS OF FINCH 3". Annals of the Rheumatic Diseases 79, Suppl 1 (junho de 2020): 312–13. http://dx.doi.org/10.1136/annrheumdis-2020-eular.288.

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Background:Patients (pts) with rheumatoid arthritis (RA) with poor prognostic factors (PPF) are at risk for RA progression if disease activity is not rapidly controlled. In FINCH 3 (NCT02886728), filgotinib (FIL)—an oral, potent, selective JAK1 inhibitor—was effective relative to methotrexate monotherapy (MTX mono) in MTX-naïve patients with ≥1 PPF—erosions, seropositivity for rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP), or hsCRP ≥4 mg/L.1Objectives:This post hoc analysis examined FIL efficacy in FINCH 3 pts with multiple PPF.Methods:The global, phase 3, double-blind, active-controlled FINCH 3 study randomised MTX-naïve pts with moderately to severely active RA 2:1:1:2 to oral FIL 200 mg once daily + MTX ≤20 mg weekly, FIL 100 mg + MTX, FIL 200 mg mono, or PBO + MTX up to week (W)52. This subgroup analysis included pts with all 4 of the following PPF at baseline (PPF pts): erosions, seropositivity for RF or anti-CCP, hsCRP ≥4 mg/L, and DAS(28)CRP >5.1. Comparisons were not adjusted for multiplicity.Results:Of 1249 pts randomised and treated in FINCH 3, 510 had all 4 PPF. At baseline, relative to the overall FINCH 3 population, PPF pts had longer mean disease duration (2.4 vs 2.2 years); higher mean hsCRP (27.9 vs 17.5 mg/L), mTSS (17.9 vs 13.3), DAS28(CRP) (6.3 vs 5.7), HAQ-DI (1.76 vs 1.56), CDAI (44.3 vs 39.8), and SDAI (47.1 vs 41.5); and greater frequency of seropositivity for RF (90.6% vs 67.9%), anti-CCP (92.4% vs 68.5%), or both (82.9% vs 59.6%). Efficacy in PPF pts was comparable to data from all FINCH 3 pts (Table, Figures 1–2). PPF pts receiving FIL 200 mg with or without MTX vs MTX mono had higher frequencies of ACR20/50/70 response and greater improvement in HAQ-DI at W24; responses were numerically greater for FIL 200 mg + MTX vs FIL 100 mg + MTX or FIL 200 mg mono (Table) and were evident by W12 (data not shown). Radiographic progression at W24 was lower in PPF pts receiving FIL 200 mg + MTX or FIL 200 mg mono vs MTX mono (Figure 1). Proportions of PPF pts receiving FIL 200 mg with or without MTX who achieved DAS28(CRP) <2.6, CDAI ≤2.8, SDAI ≤3.3, and Boolean remission at W24 (Figure 2) were larger vs pts receiving MTX mono and numerically greater vs pts receiving FIL 100 mg + MTX.Table.Efficacy outcomes in patients with 4 PPF and all FINCH 3 patients at W24FIL 200 mg+ MTXFIL 100 mg+ MTXFIL 200 mg monoMTXmonoPPFAllPPFAllPPFAllPPFAlln1724168520787210166416ACR20, %85.5*81.0***83.580.2*81.678.174.771.4ACR50, %70.3***61.5***58.857.0**59.858.1**48.245.7ACR70, %54.1***43.8***37.640.1***43.7*40.0***28.326.0HAQ-DIa−1.2***−0.94***−1.0*−0.90**−1.0*−0.89*−0.9−0.79aMean change from baseline.*, p <0.05;**, p <0.01;***, p <0.001 vs MTX mono, not adjusted for multiplicity.FIL, filgotinib; mono, monotherapy; MTX, methotrexate; PPF, poor prognostic factors.Conclusion:FIL treatment provided rapid and deep disease control including higher rates of remission and other clinical outcomes, improved physical function, and less radiographic progression compared with MTX alone in MTX-naïve pts with RA with 4 PPF, a population at risk for severe progressive disease. In pts with 4 PPF, W24 remission rates following FIL 200 mg with or without MTX were higher vs MTX mono and numerically higher vs FIL 100 mg + MTX.References:[1]Westhovens et al.Ann Rheum Dis2019;78(Suppl2):259–60.Disclosure of Interests:Daniel Aletaha Grant/research support from: AbbVie, Novartis, Roche, Consultant of: AbbVie, Amgen, Celgene, Lilly, Medac, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi Genzyme, Speakers bureau: AbbVie, Celgene, Lilly, Merck, Novartis, Pfizer, Sanofi Genzyme, UCB, Rene Westhovens Grant/research support from: Celltrion Inc, Galapagos, Gilead, Consultant of: Celltrion Inc, Galapagos, Gilead, Speakers bureau: Celltrion Inc, Galapagos, Gilead, Cecile Gaujoux-Viala Consultant of: AbbVie; Amgen; Bristol-Myers Squibb; Celgene; Gilead Sciences, Inc.; Janssen; Lilly; Medac; Merck-Serono; Mylan; Nordic Pharma; Novartis; Pfizer; Roche; Sandoz; Sanofi; UCB, Speakers bureau: AbbVie; Amgen; Bristol-Myers Squibb; Celgene; Gilead Sciences, Inc.; Janssen; Lilly; Medac; Merck-Serono; Mylan; Nordic Pharma; Novartis; Pfizer; Roche; Sandoz; Sanofi; UCB, Giovanni Adami: None declared, Alan Matsumoto Grant/research support from: AbbVie; BMS; Eli Lilly; Galapagos; Gilead Sciences, Inc.; GSK; Janssen; Novartis; Pfizer; Sanofi; UCB; Regeneron, Consultant of: AbbVie; Gilead Sciences, Inc.; GSK; Novartis, Paul Bird Consultant of: AbbVie, Celgene Corporation, Eli Lilly, Janssen, Novartis, Pfizer – advisor, Speakers bureau: AbbVie, Celgene Corporation, Eli Lilly, Janssen, Novartis, Pfizer, Osvaldo Messina Speakers bureau: Amgen; Americas Health Foundation; Pfizer, Maya H Buch Grant/research support from: Pfizer, Roche, and UCB, Consultant of: Pfizer; AbbVie; Eli Lilly; Gilead Sciences, Inc.; Merck-Serono; Sandoz; and Sanofi, Beatrix Bartok Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Zhaoyu Yin Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Ying Guo Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Thijs Hendrikx Shareholder of: Galapagos (share/warrant holder), Employee of: Galapagos, Gerd Rüdiger Burmester Consultant of: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Speakers bureau: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma
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Ardiyansyah, Arief, Eko Setiawan e Bahroin Budiya. "Moving Home Learning Program (MHLP) as an Adaptive Learning Strategy in Emergency Remote Teaching during the Covid-19 Pandemic". JPUD - Jurnal Pendidikan Usia Dini 15, n.º 1 (30 de abril de 2021): 1–21. http://dx.doi.org/10.21009/jpud.151.01.

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The Covid-19 pandemic had a dangerous impact on early-childhood education, lost learning in almost all aspects of child development. The house-to-house learning, with the name Moving Home Learning Program (MHLP), is an attractive offer as an emergency remote teaching solution. This study aims to describe the application of MHLP designed by early-childhood education institutions during the learning process at home. This study used a qualitative approach with data collection using interviews, observation, and documentation. The respondents involved in the interview were a kindergarten principal and four teachers. The research data were analyzed using the data content analysis. The Findings show that the MHLP has proven to be sufficiently in line with the learning needs of early childhood during the Covid-19 pandemic. Although, the application of the MHLP learning model has limitations such as the distance from the house that is far away, the number of meetings that are only once a week, the number of food and toy sellers passing by, disturbing children's concentration, and the risk of damage to goods at home. The implication of this research can be the basis for evaluating MHLP as an adaptive strategy that requires the attention of related parties, including policy makers, school principals, and teachers for the development of new, more effective online learning models. Keywords: Moving Home Learning Program (MHLP), Children Remote Teaching References:Abdollahi, E., Haworth-Brockman, M., Keynan, Y., Langley, M. J., & Oghadas, S. M. (2020). Simulating the effect of school closure during COVID-19 outbreaks in Ontario , Canada. BMC Medicine, 1–8. https://doi.org/https://doi.org/10.1186/s12916-020-01705-8 Arends, R. I., & Kilcher, A. (2010). 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Livros sobre o assunto "Guo ying di 228 chang"

1

Guo ying di 228 chang chang zhi bian zuan wei yuan hui. 国营第二二八厂厂志. Changchun: [s.n.], 1987.

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2

Guo ying di 908 chang zhi bian zuan wei yuan hui. Guo ying di 908 chang zhi (1953-1985). [Taiyuan Shi: Guo ying di 908 chang], 1993.

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3

Guo ying di wu yi ling si chang. Guo ying di wu yi ling si chang zhi. [Nanzhao Xian]: [Guo ying di wu yi ling si chang], 2008.

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4

Xi bei wu mian zhi bian ji shi. Guo ying xi bei di 5 mian fang zhi chang zhi, 1954-1986. [Xi'an: Guo ying xi bei di 5 mian fang zhi chang], 1987.

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5

dong, Weng xiang. Zhong guo pin pai di cheng ben ying xiao ce lüe. Zhong qing: Zhong qing chu ban she, 2003.

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6

Guo ying di er wu ba chang chang zhi bian zuan wei yuan hui. 國營第二五八厰誌(第一卷), 1964-1986. China: [s.n.], 1988.

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7

Wang, Hengshan. 经纬天地谱春秋: Guo ying Shijiazhuang di er mian fang zhi chang shi zhi, (1945-1990). Beijing: Guang ming ri bao chu ban she, 1992.

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8

Zhiyuan, Li, ed. Ji yu tu di liu zhuan gou jian wo guo min ying nong chang zhi du yan jiu. Hefei Shi: Anhui da xue chu ban she, 2009.

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9

Wang, Guiquan. Qi ye nei bu jing ji he suan zhi: Guo ying Qing hua dian qi zhi zao chang di shi jian. Xi'an: Shanxi ren min chu ban she, 1986.

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10

Shiyuan, Xu, e Hou Lijun 1975-, eds. Chang Jiang kou chao tan chen ji wu -- shui jie mian ying yang yan huan jing sheng wu di qiu hua xue guo cheng. Beijing: Ke xue chu ban she, 2007.

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