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Baseline characteristics of patients in the Chinese Bronchiectasis Registry (BE-China): a multicentre prospective cohort study 中国支气管扩张登记(BE-China)患者的基线特征:一项多中心前瞻性队列研究
IF 76.2 1区 医学 Q1 CRITICAL CARE MEDICINE Pub Date : 2025-01-10 DOI: 10.1016/s2213-2600(24)00364-3
Jin-Fu Xu, Hui-Zhen Zheng, Hai-Wen Lu, Ling-Wei Wang, Bin Wu, Xiao-Dong Lv, Hong Luo, Jian Feng, Yuan-Yuan Li, Lin Liu, Jin-Guang Jia, Wei-Qiang Mo, Hong-Yan Gu, Jing-Bo Jiang, Dao-Xin Wang, Bin Wang, Li Li, Zhi Yuan, Wen Li, Min Xie, Min Zhang
<h3>Background</h3>Bronchiectasis is a disease with a global impact, but most published data come from high-income countries. We aimed to describe the clinical characteristics of patients with bronchiectasis in China.<h3>Methods</h3>The Chinese Bronchiectasis Registry (BE-China) is a prospective, observational cohort enrolling patients from 111 hospitals in China. Data on demographics, comorbidities, and aetiological testing results were collected from adult patients with bronchiectasis at baseline and annual follow-up. Patients who met the inclusion criteria (age ≥18 years; received chest high-resolution CT in the past year showing bronchiectasis affecting one or more lung lobes; and clinical history consistent with bronchiectasis, including chronic cough, daily sputum production, and history of exacerbations) were included. Patients with known cystic fibrosis were excluded. To investigate variations according to different economic regions, two groups were compared based on whether per capita disposable income of residents was greater than US$5553. Clinical characteristics were compared with the European (EMBARC) registry and other national registries.<h3>Findings</h3>Between Jan 10, 2020, and March 31, 2024, 10 324 patients from 97 centres were included in the study. Among 9501 participants with available data, the most common cause of bronchiectasis was post-infective disease (4101 [43·2%] patients), followed by idiopathic (2809 [29·6%] patients). 6676 (70·0%) of 9541 patients with available data had at least one exacerbation in the year before enrolment and 5427 (57·2%) of 9489 patients with available data were hospitalised at least once due to exacerbations. Treatments commonly used in high-income countries, such as inhaled antibiotics and macrolides, were infrequently used in China. Implementation of airway clearance in China was scarce, with only 1177 (12·2%) of 9647 patients having used at least one method of airway clearance. Compared with upper-middle-income regions, patients from lower-middle-income regions were younger (61·0 years [SD 14·0] <em>vs</em> 63·9 years [14·2]) with a higher proportion of pulmonary comorbidities (521 [17·8%] of 2922 patients <em>vs</em> 639 [8·6%] of 7402 with chronic obstructive pulmonary disease and 194 [6·6%] of 2922 patients <em>vs</em> 364 [4·9%] of 7402 patients with asthma), a higher tuberculosis burden (442 [16·0%] of 2768 patients <em>vs</em> 715 [10·6%] of 6733 patients), more severe radiological involvement (1160 [42·4%] of 2736 patients <em>vs</em> 2415 [35·4%] of 6816 patients with cystic bronchiectasis), more exacerbations (median 1·4 [IQR 0–2] in both groups; mean 1·4 [SD 1·6] <em>vs</em> 1·2 [1·4] in the previous year) and hospitalisations (1662 [60·6%] of 2743 patients <em>vs</em> 3765 [55·8%] of 6746 patients hospitalised at least once in the previous year), and poorer quality of life (median 57·4 [IQR 53·5–63·1] <em>vs</em> 58·7 [54·8–64·8] assessed by the Bronchiectasis Health Questionnai
背景:支气管扩张是一种影响全球的疾病,但大多数已发表的数据来自高收入国家。我们的目的是描述中国支气管扩张患者的临床特征。方法中国支气管扩张登记(BE-China)是一项前瞻性观察队列研究,纳入了来自中国111家医院的患者。在基线和年度随访中收集成年支气管扩张患者的人口统计学数据、合并症和病因学检测结果。符合纳入标准的患者(年龄≥18岁;过去一年接受胸部高分辨率CT检查,显示支气管扩张影响一个或多个肺叶;包括与支气管扩张相一致的临床病史(包括慢性咳嗽、每日痰量和加重史)。排除已知囊性纤维化的患者。为了调查不同经济区域的差异,根据居民人均可支配收入是否大于5553美元对两组进行了比较。临床特征与欧洲(EMBARC)登记处和其他国家登记处进行比较。在2020年1月10日至2024年3月31日期间,来自97个中心的10324名患者被纳入研究。在9501名有资料的参与者中,最常见的支气管扩张原因是感染后疾病(4101例[43.2%]),其次是特发性疾病(2809例[29.6%])。9541例可获得数据的患者中有6676例(70%)在入组前一年至少有一次病情加重,9489例可获得数据的患者中有5427例(57.2%)因病情加重至少住院一次。高收入国家常用的治疗方法,如吸入抗生素和大环内酯类药物,在中国很少使用。中国实施气道清除的情况很少,9647例患者中只有1177例(12.2%)使用了至少一种气道清除方法。与中高收入地区相比,中低收入地区患者更年轻(66.1岁[SD 14.0]对63.9岁[14.2]),肺部合合症比例更高(2922例慢性阻塞性肺病患者中521例[17.8%]对7402例慢性阻塞性肺病患者中639例[8.6%],2922例哮喘患者中194例[6.6%]对7402例哮喘患者中364例[4.9%]),结核病负担更高(2768例患者中442例[16.0%]对6733例患者中715例[10.6%])。更严重的影像学损害(2736例患者中1160例[42.4%]vs 6816例患者中2415例[35.4%]),更严重的加重(两组中位数为1.4 [IQR 0-2];平均1.4[标准差1.6]比上一年的1.2[1.4])和住院(2743例患者中1662例[66%]比上一年至少住院一次的6746例患者中3765例[55.8%]),以及较差的生活质量(经支气管扩张健康问卷评估的中位数57.4 [IQR 55.3 - 63.1]比58.7[58.4 - 68.4])。与欧洲和印度的队列相比,中国支气管扩张患者的临床特征存在差异。支气管扩张在低收入地区更为严重,加重负担更高。中国支气管扩张患者的管理急需规范和改进。国家自然科学基金、上海市教委创新项目、上海市科学技术委员会项目、上海申康发展中心项目。摘要的中文译文见补充资料部分。
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引用次数: 0
What does the expanding CFTR modulator programme mean for people with cystic fibrosis? 扩大CFTR调节剂规划对囊性纤维化患者意味着什么?
IF 76.2 1区 医学 Q1 CRITICAL CARE MEDICINE Pub Date : 2025-01-10 DOI: 10.1016/s2213-2600(24)00427-2
Kevin W Southern
No Abstract
没有抽象的
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引用次数: 0
Burden of RSV infections among young children in primary care: a prospective cohort study in five European countries (2021–23) 初级保健中幼儿呼吸道合胞病毒感染负担:五个欧洲国家的前瞻性队列研究(2021-23)
IF 76.2 1区 医学 Q1 CRITICAL CARE MEDICINE Pub Date : 2025-01-09 DOI: 10.1016/s2213-2600(24)00367-9
Sarah F Hak, Valérie D V Sankatsing, Joanne G Wildenbeest, Roderick P Venekamp, Beatrice Casini, Caterina Rizzo, Mathieu Bangert, Daan Van Brusselen, Elizabeth Button, María Garcés-Sánchez, César García Vera, Rolf Kramer, Simon de Lusignan, Marc Raes, Adam Meijer, John Paget, Jojanneke van Summeren
<h3>Background</h3>The majority of respiratory syncytial virus (RSV) infections in young children are managed in primary care, however, the disease burden in this setting remains poorly defined.<h3>Methods</h3>We did a prospective cohort study in primary care settings in Belgium, Italy, Spain, the Netherlands, and the UK during the RSV seasons of 2020–21 (UK only; from Jan 1, 2021), 2021–22, and 2022–23. Children aged younger than 5 years presenting to their general practitioner or primary care paediatrician with symptoms of an acute respiratory tract infection were eligible for RSV testing. Children who tested positive for RSV were consented and followed up for 30 days via a physician clinical report (initial primary care visit on day 1) and two parent-report questionnaires (days 14 and 30). We assessed the burden of RSV in terms of clinical course (symptoms, illness duration, and complications), health-care resource utilisation (primary care visits, emergency department visits, hospitalisation rate, and medication use), and societal impact (daycare or school absence and parental work absence) for the 30-day follow-up period.<h3>Findings</h3>Among 3414 tested children, 1124 (32·9%; 95% CI 31·3–34·5) tested positive for RSV. Among children with data on age, RSV positivity rate was 38·9% (36·1–41·7; n=466 of 1198) in children younger than 1 year and 25·9% (24·0–27·9; n=513 of 1979) in those aged 1 to <5 years. Of the 1124 RSV-positive children, 878 (78·1%) were enrolled and had day 1 data collected (median age 11·1 months [IQR 6·0–22·0]; 446 [50·9%] boys and 431 [49·1%] girls [N=877]). RSV illness lasted a mean of 11·7 days (95% CI 11·2–12·2; n=794). At day 14 and day 30, any remaining symptoms were reported in 451 of 804 (56·1% [95% CI 52·6–59·6]) and 261 of 724 (36·0% [32·6–39·7]) children. The mean number of primary care visits per child ranged from 1·4 (95% CI 1·2–1·6; the Netherlands) to 3·0 (2·8–3·3; Spain), and was higher in children younger than 1 year (2·7 visits [2·4–2·9]) than in those aged 1 to <5 years (2·1 [1·9–2·2]). Prescribed medication use varied, from 25 of 96 children (26·0% [95% CI 17·6–36·0]; the UK) to 228 of 297 children (76·8% [71·5–81·5]; Italy), with bronchodilators and antibiotics being the most commonly prescribed medicines across all countries. Prescribed medication use was reported in 258 of 418 children aged 1 to <5 years (61·7% [56·9–66·4]) and 196 of 394 children younger than 1 year (49·7% [44·7–54·8]). Missed working days by parents due to their child's RSV illness were reported in 340 of 744 cases (45·7% [42·1–49·4]); the mean number of missed workdays ranged from 1·3 days (95% CI 0·5–2·2) in Spain to 4·1 days (3·3–5·0) in Belgium.<h3>Interpretation</h3>RSV infections in children younger than 5 years in primary care are associated with substantial symptomatology, health-care utilisation, and parental work absence. Notable differences in RSV burden existed across countries, likely due to differences in p
背景:大多数幼儿呼吸道合胞病毒(RSV)感染在初级保健中得到管理,然而,这种情况下的疾病负担仍然不明确。方法:我们在比利时、意大利、西班牙、荷兰和英国的初级保健机构进行了一项前瞻性队列研究,研究时间为2020-21年RSV季节(仅英国;从2021年1月1日起),2021 - 22日和2022-23日。向全科医生或初级保健儿科医生提出急性呼吸道感染症状的5岁以下儿童有资格进行RSV检测。RSV检测呈阳性的儿童被同意并通过医生临床报告(第1天的初次初级保健访问)和两次父母报告问卷(第14天和第30天)进行了30天的随访。在30天的随访期间,我们从临床病程(症状、病程和并发症)、医疗资源利用(初级保健就诊、急诊就诊、住院率和药物使用)和社会影响(日托或上学缺勤和父母缺勤)方面评估了RSV的负担。结果3414例患儿中,1124例(32.9%);95% CI(33.1 ~ 34.5)为RSV阳性。在有年龄资料的儿童中,RSV阳性率为38.9% (36.1 ~ 41.7;1岁以下儿童N =466 / 1198), 25.9% (24.0 - 27.9;N =513(1979)),年龄在1至5岁之间。在1124例rsv阳性儿童中,878例(78.1%)入组并收集了第1天的数据(中位年龄11.1个月[IQR 6.0 - 22.0];男孩446例(50.9%),女孩431例(49.1%)[N=877])。RSV疾病平均持续11.7天(95% CI 11.2 - 12.2;n = 794)。在第14天和第30天,804名儿童中有451名(56.1% [95% CI 52.6 - 59.6])和724名儿童中有261名(36.0%[32.6 - 39.7])报告了任何剩余症状。每个儿童的平均初级保健就诊次数为1.4次(95% CI为1.2 - 1·6;荷兰)至3.0 (2.8 - 3.3;1岁以下儿童(2·7次[2·4-2·9])高于1 ~ 5岁儿童(2·1次[1·9 - 2·2])。处方药物的使用各不相同,96名儿童中有25名(26.0% [95% CI 17.6 - 36.0];英国)至297名儿童中的228名(76.8% [71.5 - 81.5]);支气管扩张剂和抗生素是所有国家最常用的处方药。418名1 - 5岁儿童中有258名(61.7%[55.9 - 66.4])和394名1岁以下儿童中有196名(49.7%[44.7 - 58.4])报告了处方药使用情况。744例病例中,有340例(45.7%[42.1 - 49.4])因儿童呼吸道合胞病毒疾病而导致父母缺勤;平均缺勤天数从西班牙的1.3天(95% CI 0.5 - 2)到比利时的4.1天(3.5 - 5.0)不等。解释:5岁以下初级保健儿童的呼吸道合胞病毒感染与实质症状、卫生保健利用和父母缺勤有关。RSV负担在各国之间存在显著差异,可能是由于初级卫生保健系统、临床实践和寻求卫生保健行为的差异。这项研究强调了在考虑实施RSV免疫规划时考虑具体国家初级保健负担估计的重要性。资助赛诺菲和阿斯利康。
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引用次数: 0
Elucidating the outpatient burden of RSV disease in children 阐明儿童呼吸道合胞病毒病的门诊负担
IF 76.2 1区 医学 Q1 CRITICAL CARE MEDICINE Pub Date : 2025-01-09 DOI: 10.1016/s2213-2600(24)00402-8
Fatimah S Dawood, Meredith L McMorrow
No Abstract
没有抽象的
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引用次数: 0
A response to therapy for COPD with dupilumab dupilumab治疗COPD的反应
IF 76.2 1区 医学 Q1 CRITICAL CARE MEDICINE Pub Date : 2025-01-03 DOI: 10.1016/s2213-2600(24)00371-0
Surya P Bhatt, Klaus F Rabe, Dave Singh, Mona Bafadhel, Claus F Vogelmeier
No Abstract
没有抽象的
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引用次数: 0
Vanzacaftor–tezacaftor–deutivacaftor for children aged 6–11 years with cystic fibrosis (RIDGELINE Trial VX21-121-105): an analysis from a single-arm, phase 3 trial Vanzacaftor-tezacaftor-deutivacaftor用于6-11岁囊性纤维化儿童(RIDGELINE试验VX21-121-105):来自单组3期试验的分析
IF 76.2 1区 医学 Q1 CRITICAL CARE MEDICINE Pub Date : 2025-01-02 DOI: 10.1016/s2213-2600(24)00407-7
Jordana E Hoppe, Ajay S Kasi, Jessica E Pittman, Renee Jensen, Lena P Thia, Philip Robinson, Pornchai Tirakitsoontorn, Bonnie Ramsey, Marcus A Mall, Jennifer L Taylor-Cousar, Edward F McKone, Elizabeth Tullis, Danieli B Salinas, Jiaqiang Zhu, Yih-Chieh Chen, Violeta Rodriguez-Romero, Patrick R Sosnay, Gwyneth Davies
<h3>Background</h3>In phase 2 trials in people with cystic fibrosis aged 18 years and older, vanzacaftor–tezacaftor–deutivacaftor has been shown to be a safe and effective, once-daily cystic fibrosis transmembrane conductance regulator (CFTR) modulator. Restoring normal CFTR function early in life has the potential to prevent manifestations of cystic fibrosis. We aimed to evaluate the safety, tolerability, efficacy, and pharmacokinetics of vanzacaftor–tezacaftor–deutivacaftor in children with cystic fibrosis aged 6–11 years.<h3>Methods</h3>In this multicentre, single-arm, phase 3 trial (RIDGELINE Trial VX21-121-105), participants were enrolled across 33 clinical sites that care for children with cystic fibrosis in eight countries (Australia, France, Germany, Netherlands, Sweden, Switzerland, the UK, and the USA). Eligible participants were aged 6–11 years with at least one elexacaftor–tezacaftor–ivacaftor-responsive <em>CFTR</em> variant, FEV<sub>1</sub> % predicted of 60% or higher, and stable cystic fibrosis as determined by investigators. Before study treatment, participants were either on stable elexacaftor–tezacaftor–ivacaftor for at least 28 days before screening or received the combination for a 4-week run-in period. Participants then received vanzacaftor–tezacaftor–deutivacaftor (<40 kg bodyweight: vanzacaftor 12 mg, tezacaftor 60 mg, and deutivacaftor 150 mg orally as three fixed-dose combination tablets once daily; ≥40 kg bodyweight: vanzacaftor 20 mg, tezacaftor 100 mg, and deutivacaftor 250 mg orally as two fixed-dose combination tablets once daily (manufactured by Patheon Pharmaceuticals, Cincinnati, OH, USA) from day 1 for 24 weeks. The primary endpoint was safety and tolerability, as measured by adverse events, vital signs, clinical laboratory values, electrocardiograms, and pulse oximetry. Endpoints were analysed in all participants who received at least one dose of vanzacaftor–tezacaftor–deutivacaftor. This trial is registered with <span><span>ClinicalTrials.gov</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>, <span><span>NCT05422222</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>, and evaluation of the 6–11-year-old cohort is complete.<h3>Findings</h3>Between Feb 6 and May 18, 2023, 83 children were screened, of whom five were not eligible, and 78 children aged 6-11 years received at least one dose of vanzacaftor–tezacaftor–deutivacaftor. Median age was 9·3 years (IQR 7·6–10·4), 34 (44%) of 78 participants were female, 44 (56%) were male, 71 (91%) were White, one (1%) was Black or African American, and one (1%) was of multiple races. The analysis for these data was completed on Dec 15, 2023. Median expos
在18岁及以上囊性纤维化患者的2期试验中,vanzacaftor-tezacaftor-deutivacaftor已被证明是一种安全有效的、每日一次的囊性纤维化跨膜传导调节剂(CFTR)。在生命早期恢复正常的CFTR功能有可能预防囊性纤维化的表现。我们的目的是评估vanzacaftor-tezacaftor-deutivacaftor在6-11岁囊性纤维化儿童中的安全性、耐受性、有效性和药代动力学。在这项多中心、单臂、3期试验(RIDGELINE试验VX21-121-105)中,参与者来自8个国家(澳大利亚、法国、德国、荷兰、瑞典、瑞士、英国和美国)33个治疗囊性纤维化儿童的临床站点。符合条件的参与者年龄为6-11岁,至少有一种elexacator - tezacator - ivacator -responsive CFTR变体,FEV1预测为60%或更高,并且由研究人员确定为稳定的囊性纤维化。在研究治疗之前,参与者要么在筛选前至少28天使用稳定的elexaftor - tezactor - ivacaftor,要么在4周的磨合期内接受联合治疗。然后,参与者服用vanzacactor - tezacactor - deutivacactor(体重40公斤):vanzacactor 12mg, tezacactor 60mg, deutivacactor 150mg,口服3片固定剂量组合片,每日一次;体重≥40 kg: vanzacaftor 20 mg, tezacaftor 100 mg, deutivacaftor 250 mg,口服2片固定剂量联合片,每日1次(由Patheon Pharmaceuticals, Cincinnati, OH, USA生产),从第1天开始,连续24周。主要终点是安全性和耐受性,通过不良事件、生命体征、临床实验室值、心电图和脉搏血氧测定来衡量。终点分析了所有接受至少一剂vanzacactor - tezacactor - deutivacactor的参与者。该试验已在ClinicalTrials.gov注册,编号NCT05422222, 6 - 11岁队列的评估已经完成。在2023年2月6日至5月18日期间,筛查了83名儿童,其中5名不符合条件,78名6-11岁的儿童接受了至少一剂vanzacaftor-tezacaftor-deutivacaftor。78名参与者中,女性34人(44%),男性44人(56%),白人71人(91%),黑人或非裔美国人1人(1%),多种族1人(1%)。对这些数据的分析于2023年12月15日完成。参与者暴露于vanzacactor - tezacactor - deutivacactor的中位数为168天(IQR 166-170)。78名受试者中有75名(96%)出现不良事件,均为轻度或中度;最常见的事件一般与囊性纤维化表现一致,包括咳嗽(36例[46%])、发热(16例[21%])、头痛(14例[18%])、囊性纤维化感染性肺加重(13例[17%])、口咽部疼痛(13例[17%])。6名(8%)参与者发生了严重的不良事件(2名患有感染性肺恶化,其中1名也未能茁壮成长;1名参与者分别有腺病毒感染、便秘、肺功能测试下降和咳嗽,1名(1%)参与者因咳嗽和疲劳等不良事件被认为可能与研究药物有关而停药。vanzactor - tezactor - deutivactor是安全且耐受性良好的,维持了从elexaftor - tezactor - ivacaftor基线预测的1%的FEV1,并进一步改善了CFTR功能。CFTR功能的改善与基线elexactor - tezactor - ivacaftor值相比,显示了早期恢复正常生理和预防囊性纤维化发生或进展的潜在机会。几乎所有参与者的汗液氯化物都低于囊性纤维化的诊断阈值(60 mmol/L),超过一半的参与者的汗液氯化物水平正常(30 mmol/L)。一项开放标签扩展研究正在收集儿童囊性纤维化的额外长期数据,以证明临床益处和安全性。这些发现将告知卫生保健提供者和囊性纤维化患者早期开始使用CFTR调节剂的益处。FundingVertex药品。
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引用次数: 0
Vanzacaftor–tezacaftor–deutivacaftor versus elexacaftor–tezacaftor–ivacaftor in individuals with cystic fibrosis aged 12 years and older (SKYLINE Trials VX20-121-102 and VX20-121-103): results from two randomised, active-controlled, phase 3 trials Vanzacaftor-tezacaftor-deutivacaftor对12岁及以上囊性纤维化患者的疗效(SKYLINE试验VX20-121-102和VX20-121-103):两项随机、主动对照的3期试验结果
IF 76.2 1区 医学 Q1 CRITICAL CARE MEDICINE Pub Date : 2025-01-02 DOI: 10.1016/s2213-2600(24)00411-9
Claire Keating, Lael M Yonker, François Vermeulen, Dario Prais, Rachel W Linnemann, Aaron Trimble, Tom Kotsimbos, Joel Mermis, Andrew T Braun, Mark O'Carroll, Sivagurunathan Sutharsan, Bonnie Ramsey, Marcus A Mall, Jennifer L Taylor-Cousar, Edward F McKone, Elizabeth Tullis, Tim Floreth, Peter Michelson, Patrick R Sosnay, Nitin Nair, Alexander Horsley
<h3>Background</h3>The goal of cystic fibrosis transmembrane conductance regulator (CFTR) modulators is to reach normal CFTR function in people with cystic fibrosis. Vanzacaftor–tezacaftor–deutivacaftor restored CFTR function in vitro and in phase 2 trials in participants aged 18 years and older resulting in improvements in CFTR function, as measured by sweat chloride concentrations and lung function as measured by spirometry. We aimed to evaluate the efficacy and safety of vanzacaftor–tezacaftor–deutivacaftor compared with standard of care elexacaftor–tezacaftor–ivacaftor in individuals with cystic fibrosis aged 12 years and older.<h3>Methods</h3>In two randomised, active-controlled, double-blind, phase 3 trials, individuals aged 12 years and older with stable cystic fibrosis with <em>F508del</em>-minimal function (SKYLINE Trial VX20-121-102) or with <em>F508del-F508del, F508del</em>-residual function, <em>F508del</em>-gating, or elexacaftor–tezacaftor–ivacaftor-responsive-non-<em>F508del</em> genotypes (SKYLINE Trial VX20-121-103) were enrolled at 126 and 159 international sites, respectively. Eligible individuals were entered into a 4-week run-in period, during which they received elexacaftor (200 mg once daily), tezacaftor (100 mg once daily), and ivacaftor (150 mg once every 12 h) as two fixed-dose combination tablets in the morning and one ivacaftor tablet in the evening. They were then randomly assigned (1:1) to either elexacaftor (200 mg once daily), tezacaftor (100 mg once daily), and ivacaftor (150 mg once every 12 h) as two fixed-dose combination tablets in the morning and one ivacaftor tablet in the evening, or vanzacaftor (20 mg once daily), tezacaftor (100 mg once daily), and deutivacaftor (250 mg once daily) as two fixed-dose combination tablets in the morning, for the 52-week treatment period. All participants received matching placebo tablets to maintain the treatment blinding. Randomisation was done using an interactive web-response system and stratified by age, FEV<sub>1</sub> % predicted, sweat chloride concentration, and previous CFTR modulator use, and also by genotype for Trial VX20-121-103. The primary endpoint for both trials was absolute change in FEV<sub>1</sub> % predicted from baseline (most recent value before treatment on day 1) through week 24 (with non-inferiority of vanzacaftor–tezacaftor–deutivacaftor shown if the lower bound of the 95% CI for the primary endpoint was –3·0 or higher). Efficacy was assessed in all participants with the intended <em>CFTR</em> genotype who were randomly assigned to treatment and received at least one dose of study treatment during the treatment period. Safety was assessed in all participants who received at least one dose of study drug during the treatment period. These trials are registered with <span><span>ClinicalTrials.gov</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0
囊性纤维化跨膜传导调节剂(CFTR)的目标是使囊性纤维化患者的CFTR功能达到正常。Vanzacaftor-tezacaftor-deutivacaftor在体外和18岁及以上参与者的2期试验中恢复了CFTR功能,通过汗液氯化物浓度测量CFTR功能,通过肺活量测定法测量肺功能。我们的目的是评估vanzacaftor-tezacaftor-deutivacaftor与标准护理方案eleexaftor - tezacaftor - ivacaftor在12岁及以上囊性纤维化患者中的疗效和安全性。方法在两项随机、主动对照、双盲、3期试验中,分别在126个和159个国际站点招募了年龄在12岁及以上的F508del-minimal功能(SKYLINE试验VX20-121-102)或F508del-F508del、f508del -残差功能、f508del -门控或elexacaftor - tezacaftor - ivacaftor-应答性非f508del基因型(SKYLINE试验VX20-121-103)的稳定囊性纤维化患者。符合条件的个体进入为期4周的磨合期,在此期间,他们在早上接受elexaftor (200mg每日一次),tezacaftor (100mg每日一次)和ivacaftor (150mg每12小时一次)作为两个固定剂量的组合片,在晚上接受一个ivacaftor片。然后,他们被随机分配(1:1),要么是elexacaftor (200 mg每日一次)、tezacaftor (100 mg每日一次)和ivacaftor (150 mg每12小时一次)作为两个固定剂量的联合片,在早上和晚上分别服用一片ivacaftor片,要么是vanzacaftor (20 mg每日一次)、tezacaftor (100 mg每日一次)和deutivacaftor (250 mg每日一次)作为两个固定剂量的联合片,在52周的治疗期间。所有的参与者都接受了匹配的安慰剂片,以维持治疗的盲性。使用交互式网络反应系统进行随机化,并根据年龄、预测FEV1 %、汗液氯化物浓度、以前使用CFTR调节剂以及试验VX20-121-103的基因型进行分层。两项试验的主要终点是从基线(治疗前第1天的最新值)到第24周预测的FEV1 %的绝对变化(如果主要终点的95% CI下限为-3·0或更高,则显示vanzacaftor-tezacaftor-deutivacaftor的非劣效性)。在所有具有预期CFTR基因型的参与者中评估疗效,这些参与者被随机分配到治疗组,并在治疗期间接受至少一剂研究治疗。在治疗期间接受至少一剂研究药物的所有参与者进行了安全性评估。这些试验已在ClinicalTrials.gov注册,编号NCT05033080(试验VX20-121-102)和NCT05076149(试验VX20-121-103),现已完成。在2021年9月14日至2022年10月18日的试验VX20-121-102中,筛选了488名个体,其中435人进入了4周的运行期,随后398人被随机分配并接受至少一剂elexacaftor-tezacaftor-ivacaftor (n=202)或vanzacaftor-tezacaftor-deutivacaftor (n=196)。中位年龄31.0岁(IQR 22.6 ~ 38.5),女性163人(41%),男性235人(59%),白人388人(97%)。在2021年10月27日至2022年10月26日的试验VX20-121-103中,筛选了699名个体,其中597名进入了为期4周的试运行期,随后随机分配573名参与者,接受至少一剂elexacaftor-tezacaftor-ivacaftor (n=289)或vanzacaftor-tezacaftor-deutivacaftor (n=284)。573名参与者中,女性280人(49%),男性293人(51%),白人532人(93%),平均年龄33.1岁(IQR 24.5 ~ 42.2)。试验VX20-121-102从基线到第24周预测的最小二乘平均fev1%的绝对变化,vanzacactor - tezacactor - deutivacactor组为0.5 (SE 0.3)个百分点,而elexacator - tezacactor - ivacaftor组为0.3 (SE 0.3)个百分点(最小二乘平均治疗差异为0.2个百分点[95% CI -0·7至1·1];试验VX20-121-103中,vanzacactor - tezacactor - deutivacactor组与elexacator - tezacactor - ivacaftor组的差异为0.2 (SE为0.3)个百分点(最小二乘平均治疗差为0.2个百分点[95% CI为- 0.05 ~ 0.9];术;0·0001)。大多数不良事件为轻度或中度,最常见的是感染性肺加重(vanzacafor - tezacafor - deutivacaftor联合组480名参与者中有133名[28%],而elexafor - tezacafor - ivacaftor联合组491名参与者中有158名[32%])、咳嗽(108名[23%]对101名[21%])、COVID-19(107名[22%]对127名[26%])和鼻咽炎(102名[21%]对95名[19%])。结论vanzacator - tezacator - deutivacator在预测FEV1 %方面不低于elexafter - tezacator - ivacator,且安全且耐受性良好。 与目前每日两次的标准治疗方案相比,每日一次给药vanzacaftor-tezacaftor-deutivacaftor减轻了治疗负担,有可能提高依从性。CFTR功能的恢复和处理的潜在变异也是应该与当前可用的CFTR调制器进行比较的考虑因素。FundingVertex药品。
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引用次数: 0
Navigating uncertainty: asthma biologics during pregnancy. 驾驭不确定性:孕期哮喘生物制剂。
IF 38.7 1区 医学 Q1 CRITICAL CARE MEDICINE Pub Date : 2025-01-01 Epub Date: 2024-08-28 DOI: 10.1016/S2213-2600(24)00248-0
Imran Howell, Aleksandra Howell, Ian Pavord
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引用次数: 0
An international consensus on the use of asthma biologics in pregnancy. 关于妊娠期使用哮喘生物制剂的国际共识。
IF 38.7 1区 医学 Q1 CRITICAL CARE MEDICINE Pub Date : 2025-01-01 Epub Date: 2024-08-28 DOI: 10.1016/S2213-2600(24)00174-7
Jennifer Naftel, David J Jackson, Matthew Coleman, Grainne d'Ancona, Liam G Heaney, Paddy Dennison, Apostolos Bossios, Hitasha Rupani

Uncontrolled asthma is associated with an increased risk of adverse perinatal outcomes. Asthma biologics reduce exacerbation frequency, are steroid sparing, and improve quality of life in people with severe asthma. However, evidence for the use and safety of asthma biologics during pregnancy is scarce, largely because pregnant women were excluded from clinical trials. To help to support clinical teams, we conducted an international modified Delphi study. 141 panellists from 32 countries who were involved in the care of people with severe asthma completed two rounds of online surveys covering key areas surrounding the use of asthma biologics in pregnancy. The results from this international Delphi study emphasise risk versus benefit discussions and shared clinical decision making, with consensus among panellists that asthma biologics can be used during conception and throughout pregnancy, initiated during pregnancy in line with prescribing criteria for non-pregnant people, and initiated or continued during breastfeeding. Collating data through international registries remains essential to inform clinical guidelines.

不受控制的哮喘会增加围产期不良后果的风险。哮喘生物制剂可降低哮喘恶化的频率,减少类固醇用量,改善重症哮喘患者的生活质量。然而,有关妊娠期使用哮喘生物制剂及其安全性的证据却很少,这主要是因为孕妇被排除在临床试验之外。为了帮助支持临床团队,我们开展了一项国际性的改良德尔菲研究。来自 32 个国家的 141 位参与重症哮喘患者治疗的专家完成了两轮在线调查,调查内容涉及妊娠期使用哮喘生物制剂的关键领域。这项国际德尔菲研究的结果强调了风险与收益的讨论和共同临床决策,小组成员一致认为哮喘生物制剂可在受孕期间和整个孕期使用,在孕期开始使用时应符合非孕妇的处方标准,并在母乳喂养期间开始使用或继续使用。通过国际登记处整理数据对于为临床指南提供信息仍然至关重要。
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引用次数: 0
Collateral caring 抵押品关怀
IF 76.2 1区 医学 Q1 CRITICAL CARE MEDICINE Pub Date : 2024-12-19 DOI: 10.1016/s2213-2600(24)00421-1
Hemmings Wu
No Abstract
没有抽象的
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引用次数: 0
期刊
Lancet Respiratory Medicine
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