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Prevalence of vaccine hesitancy in Italy: a cross-sectional study 意大利疫苗犹豫的流行:一项横断面研究
IF 13 Q1 HEALTH CARE SCIENCES & SERVICES Pub Date : 2026-04-01 Epub Date: 2026-01-31 DOI: 10.1016/j.lanepe.2026.101603
Giuseppina Lo Moro , Fabrizio Bert , Giovanna Elisa Calabrò , Mauro Giovanni Carta , Giulia Cossu , Corrado De Vito , Manuela Martella , Azzurra Massimi , Anna Odone , Paolo Ragusa , Giacomo Pietro Vigezzi , Walter Ricciardi , Roberta Siliquini

Background

Vaccine hesitancy (VH) remains a global threat, exacerbated by socio-political uncertainty. We aimed primarily to estimate VH prevalence in Italy, identifying the most susceptible subgroups, and secondarily to assess whether these patterns varied across VH dimensions.

Methods

Cross-sectional survey (web/telephone) among adults in Italy (September 2024–March 2025). The sample (n = 52,094) was nationally representative by age, gender, education, area, municipality size. The primary outcome was VH (score ≥25, adult Vaccine Hesitancy Scale, aVHS). The secondary outcomes were aVHS subscales “Lack of trust” and “Risk perception”. Post-stratification weighting for age, area, and municipality size was applied.

Findings

VH prevalence was 46.09% (95% CI: 45.65–46.53%). Multivariable models showed several associations with VH, e.g., gender, sexual orientation, ethnicity, health literacy, political and religious orientation, personal experiences, and vaccination support from community figures. Among many subgroups significant after multiple-comparison correction, the strongest differences in VH predicted probability (PP) were estimated among individuals using complementary/alternative medicine (PP = 58.5%), right-aligned (PP = 47.0%) or politically unaffiliated participants (PP = 48.4%), individuals with middle school education (PP = 48.3%), people aged 60–74 (PP = 49.0%), and participants uncertain about healthcare workers' pro-vaccination support (PP = 52.8%). While some groups, e.g., individuals with chronic conditions, inadequate health literacy, or religious participants reported higher perceived risk, others, e.g., non-binary respondents, showed higher lack of trust.

Interpretation

This study highlighted the importance of granular data to inform inclusive strategies. Key figures and politics emerged as relevant, deserving further exploration. Future research should evaluate tailored interventions for identified at-risk groups.

Funding

NextGenerationEU funding within the Italian Ministry of University and Research PNRR Extended Partnership initiative on Emerging Infectious Diseases.
疫苗犹豫(VH)仍然是一个全球性威胁,社会政治不确定性加剧了这一威胁。我们的主要目的是估计意大利的VH患病率,确定最易感的亚群,其次评估这些模式是否在VH维度上有所不同。方法意大利成年人横断面调查(网络/电话)(2024年9月- 2025年3月)。样本(n = 52,094)在年龄、性别、教育程度、地区和直辖市规模方面具有全国代表性。主要结局为VH(成人疫苗犹豫量表评分≥25分)。次要结果为aVHS量表“信任缺失”和“风险感知”。分层后对年龄、面积和市政规模进行加权。发现svh患病率为46.09% (95% CI: 45.65-46.53%)。多变量模型显示了与VH的若干关联,例如,性别、性取向、种族、卫生素养、政治和宗教取向、个人经历以及社区人士的疫苗接种支持。在许多经多重比较校正后显著的亚组中,使用补充/替代医学的个体(PP = 58.5%)、右倾(PP = 47.0%)或无政治关联的参与者(PP = 48.4%)、受过中学教育的个体(PP = 48.3%)、60-74岁的人群(PP = 49.0%)和不确定医护人员是否支持接种疫苗的参与者(PP = 52.8%)之间的VH预测概率(PP)差异最大。虽然一些群体,如慢性病患者、卫生知识不足或宗教参与者报告了更高的感知风险,但其他群体,如非二元受访者,表现出更高的信任缺失。本研究强调了细粒度数据对包容性策略的重要性。关键人物和政治的相关性显现出来,值得进一步探讨。未来的研究应该评估针对确定的高危人群的量身定制的干预措施。资助下一代意大利大学和研究部PNRR新发传染病扩展伙伴关系倡议内的欧盟资助。
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引用次数: 0
The role of welfare regimes on socioeconomic inequalities in edentulism: a cross-national analysis of 40 countries 福利制度对蛀牙现象中社会经济不平等的作用:对40个国家的跨国分析
IF 13 Q1 HEALTH CARE SCIENCES & SERVICES Pub Date : 2026-04-01 Epub Date: 2025-12-29 DOI: 10.1016/j.lanepe.2025.101578
Roger Keller Celeste , Carol Guarnizo-Herreño , Johan Fritzell , Francine S. Costa , Olalekan Ayo-Yusuf , Aluisio J. Barros , Huihua Li , Ninuk Hariyani , Donna M. Hackley , Silvana Blanco , Jorge A. Gamonal , Gerardo Maupome , Richard G. Watt , Marco Aurelio Peres

Background

We aim to evaluate the association between welfare regimes and edentulism (total tooth loss) and to investigate whether welfare regimes modify the magnitude of socioeconomic inequalities in edentulism.

Methods

The Lancet Commission on Oral Health gathered and analysed nationally representative available data from 40 high, middle- and low-income countries, collected between 2007 and 2018. The study included 117,397 individuals 20 years or older. The outcome was edentulism, defined as the absence of all natural teeth. We categorised countries into seven welfare regimes, which served as both the primary exposure and an effect modifier. Individual-level variables included sex, age and a composite measure of socioeconomic position: “wealth” measured in quintiles. Inverse probability of treatment weight and multilevel logistic regression were employed to estimate the odds of being edentulous, and cross–level interaction terms between wealth and country factors.

Findings

Individuals at the lowest wealth quintile had the highest prevalence of edentulism in all regimes. The highest age-sex standardised prevalence was found in Eastern European countries (8.4%, 95% Confidence Interval: 7.6–9.3), followed by Corporative (8.1%, 95% CI: 7.0–9.3), while the lowest was among the Insecurity regime (0.8%, 95% CI: 0.4–1.5), followed by the Scandinavian regime (4.7%, 95% CI: 3.5–6.1). Liberal countries presented the highest magnitude of absolute and relative inequalities, where the lowest quintile had OR = 20.6 (95% CI: 15.3–27.8) times higher likelihood of being edentulous and 17.3 percentage points (pp) higher prevalence. Low-income countries in the Insecurity regime presented the lowest level of inequality. Among high- and upper-middle income countries, the Scandinavian regime had the lowest absolute inequalities (5.5 pp difference between highest and lowest quintiles). The Informal Security regime had the lowest relative differences between the highest and lowest quintiles (OR = 2.20, 95% CI: 1.06–4.59).

Interpretation

Our findings indicate that some welfare regime policies may enhance oral health while decreasing socioeconomic inequalities. Higher prevalence and inequalities among industrialised countries may reflect higher levels of oral health hazards.

Funding

This was partially supported by a National Institute for Health and Care Research (UK) grant number 132731.
我们的目的是评估福利制度和全牙缺失之间的关系,并调查福利制度是否改变了全牙缺失中社会经济不平等的程度。《柳叶刀》口腔健康委员会收集并分析了2007年至2018年期间从40个高、中、低收入国家收集的具有全国代表性的现有数据。这项研究包括117,397名20岁或以上的人。结果是无牙症,定义为没有所有天然牙齿。我们将各国分为七种福利制度,这些制度既是主要的暴露因素,也是影响调节因素。个人层面的变量包括性别、年龄和社会经济地位的综合衡量标准:以五分位数衡量的“财富”。采用治疗权重的逆概率和多水平逻辑回归来估计无牙的几率,以及财富和国家因素之间的跨水平相互作用项。研究发现,在所有国家中,财富最低的五分之一的人患蛀牙症的比例最高。年龄-性别标准化患病率最高的是东欧国家(8.4%,95%可信区间:7.6-9.3),其次是联合国家(8.1%,95%可信区间:7.0-9.3),最低的是不安全感国家(0.8%,95%可信区间:0.4-1.5),其次是斯堪的纳维亚国家(4.7%,95%可信区间:3.5-6.1)。自由国家的绝对不平等和相对不平等程度最高,其中最低五分之一的无牙可能性高出20.6倍(95% CI: 15.3-27.8),患病率高出17.3个百分点(pp)。不安全制度下的低收入国家的不平等程度最低。在高收入和中高收入国家中,斯堪的纳维亚政权的绝对不平等程度最低(最高和最低五分之一之间的差距为5.5个百分点)。非正式安全制度在最高和最低五分位数之间的相对差异最小(OR = 2.20, 95% CI: 1.06-4.59)。我们的研究结果表明,一些福利制度政策可以在减少社会经济不平等的同时促进口腔健康。工业化国家中较高的患病率和不平等现象可能反映出较高的口腔健康危害程度。该研究部分由英国国家健康与护理研究所资助,资助号为132731。
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引用次数: 0
Diabetes community calls for quality standards for continuous glucose monitoring devices 糖尿病社区呼吁制定连续血糖监测设备的质量标准。
IF 13 Q1 HEALTH CARE SCIENCES & SERVICES Pub Date : 2026-03-01 Epub Date: 2026-02-03 DOI: 10.1016/j.lanepe.2026.101598
Francesco Giorgino , Tadej Battelino , Stefano Del Prato , Rahab Hashim , Sabine E. Hofer , Sufyan Hussain , Kasia Karpinska , Tom Melvin , Eric Renard , Campbell Hutton , Jannet Svensson , Bart Torbeyns , Petra Wilson , Chantal Mathieu
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引用次数: 0
Incidence and spatial variation of Parkinson's disease in the Netherlands (2017–2022): a population-based study 荷兰帕金森病的发病率和空间变化(2017-2022):一项基于人群的研究
IF 13 Q1 HEALTH CARE SCIENCES & SERVICES Pub Date : 2026-03-01 Epub Date: 2026-01-21 DOI: 10.1016/j.lanepe.2025.101565
Mariana Simões , Susan Peters , Anke Huss , Sirwan K.L. Darweesh , Bastiaan R. Bloem , Roel Vermeulen

Background

Parkinson's disease (PD) is a growing public health concern with a largely unknown aetiology. Understanding temporal trends, demographic drivers, and regional variations in PD risk is critical for guiding healthcare planning and identifying potential environmental and socioeconomic risk factors. We aimed to investigate the incidence and spatial distribution of PD in the Netherlands from 2017 to 2022, and examined demographic and socioeconomic disparities in PD risk.

Methods

We conducted a nationwide, population-based study leveraging complementary strengths of multiple independent administrative health records linked to demographic and socioeconomic data. Incident PD cases were identified using a newly developed algorithm integrating mortality records, hospital data, health insurance claims, and medication prescriptions. We estimated overall and stratified age- and sex-internally standardized PD incidence rates (IRs). Spatial variations in PD risk were assessed using Bayesian hierarchical models to generate smoothed relative risk estimates at a fine-grained neighbourhood level.

Findings

Between 2017 and 2022, we identified 22,343 incident PD cases in a population of 19,995,771 individuals (totalling 105,027,472 person-years at risk). Overall standardized IR was relatively stable across the evaluated time at 21.8 (95% confidence interval (CI): 21.6–22.1) per 100,000 person-years at risk. Incidence increased with age (peaking at 75–85 years) and was higher in men than women, in individuals with higher socioeconomic position, and residents of the northern provinces. Spatial analysis revealed significant geographic clustering of PD risk, which did not ecologically align with major environmental indicators such as air pollution, agricultural activity, or urbanization.

Interpretation

The multifaceted algorithm offers a robust PD case ascertainment tool that allowed for a comprehensive nationwide assessment of PD incidence. In the Netherlands, this new approach uncovered regional disparities in PD risk that are not readily explained by known environmental indicators, warranting further investigation into potential environmental and socioeconomic determinants.

Funding

Woelse Waard, Gieskes-Strijbis, and Ministry of Agriculture, Fisheries, Food Security and Nature of the Netherlands.
背景:帕金森病(PD)是一个日益受到关注的公共卫生问题,其病因在很大程度上是未知的。了解PD风险的时间趋势、人口驱动因素和区域差异对于指导医疗保健计划和识别潜在的环境和社会经济风险因素至关重要。我们旨在调查2017年至2022年荷兰PD的发病率和空间分布,并检查PD风险的人口统计学和社会经济差异。方法:我们开展了一项全国性的、以人口为基础的研究,利用与人口统计和社会经济数据相关的多个独立行政健康记录的互补优势。使用一种新开发的算法,综合死亡率记录、医院数据、健康保险索赔和药物处方,确定偶发性PD病例。我们估计了总体和分层的年龄和性别内部标准化PD发病率(IRs)。使用贝叶斯分层模型评估帕金森病风险的空间变化,以在细粒度的社区水平上生成平滑的相对风险估计。研究结果:在2017年至2022年期间,我们在19,995,771人的人群中确定了22,343例PD病例(总计105,027,472人年的风险)。总体标准化IR在整个评估时间内相对稳定,为每100,000人年21.8(95%置信区间(CI): 21.6-22.1)。发病率随着年龄的增长而增加(在75-85岁达到高峰),男性高于女性、社会经济地位较高的个体和北部省份的居民。空间分析显示,PD风险具有显著的地理聚类性,与空气污染、农业活动或城市化等主要环境指标在生态上不一致。解释:多方面的算法提供了一个强大的PD病例确定工具,允许对PD发病率进行全面的全国评估。在荷兰,这种新方法揭示了PD风险的地区差异,这些差异不容易用已知的环境指标来解释,需要进一步调查潜在的环境和社会经济决定因素。资助:Woelse Waard, Gieskes-Strijbis和荷兰农业、渔业、粮食安全和自然资源部。
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引用次数: 0
Subphenotype- and complication-guided adjunctive fosfomycin versus standard monotherapy in Staphylococcus aureus bacteraemia: pooled analysis of two randomised trials 亚表型和并发症引导的辅助磷霉素与标准单药治疗金黄色葡萄球菌菌血症:两项随机试验的汇总分析
IF 13 Q1 HEALTH CARE SCIENCES & SERVICES Pub Date : 2026-03-01 Epub Date: 2026-02-17 DOI: 10.1016/j.lanepe.2026.101611
Francesc Escrihuela-Vidal , Julia García Larrauri , Joaquín López-Contreras , Gorane Euba , Andrea Vázquez , Silvia Gómez-Zorrilla , Luis Eduardo López-Cortés , Oriol Gasch , Eduardo Aparicio-Minguijón , Rosa Escudero-Sánchez , María Teresa Pérez-Rodríguez , Dolors Rodríguez-Pardo , Alfredo Jover-Sáenz , Graciano García-Pardo , Jesús Rodríguez-Baño , Miquel Pujol , Jordi Carratalà , Belén Gutiérrez-Gutiérrez
<div><h3>Background</h3><div>Randomised trials of combination therapies for <em>S. aureus</em> bacteraemia (SAB) have failed to improve clinical outcomes—likely reflecting the lack of risk-targeted patient selection. The FEN-AUREUS classification enables early risk stratification based on clinical subphenotypes. We aimed to validate this framework in a pooled trial cohort and assess whether combining subphenotypes with IDSA-defined complicated SAB could identify patients most likely to benefit from adjunctive fosfomycin.</div></div><div><h3>Methods</h3><div>We conducted a post-hoc analysis of individual-level data from two multicentre randomised trials evaluating adjunctive fosfomycin in SAB. Participants were classified according to the FEN-AUREUS framework into phenotypes and risk subphenotypes. Associations between subphenotype, complicated bacteraemia, and 60-day mortality as the primary outcome and 30-day mortality and 8-week treatment success as secondary outcomes were assessed. A DOOR analysis provided an integrated assessment of overall outcomes. This study is registered with <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>, <span><span>NCT07155590</span><svg><path></path></svg></span>.</div></div><div><h3>Findings</h3><div>Among 369 patients (median age 68 years, IQR 56–78; 262/369 [68·8%] male), high-risk subphenotypes were associated with greater 60-day mortality (23·2% versus 6·6%; risk ratio [RR] 3·49, 95% confidence interval [CI] 1·87–6·52; adjusted hazard ratio [aHR] 3·38, 1·69–6·78), regardless of complication status. Combining risk subphenotypes with the IDSA classification showed heterogeneity in response to adjunctive fosfomycin. In patients with low-risk and uncomplicated SAB (n = 107), 60-day mortality was low with both monotherapy and adjunctive fosfomycin (2·1% versus 3·4%; risk difference [RD] −1·3% [95% CI −7·4 to 4·8]; p = 0·68), and treatment success at week 8 exceeded 89%. In the intermediate strata, 60-day mortality was 18·8% with monotherapy versus 7·4% (RD 11·3% [95% CI −5·4 to 28·1]; p = 0·20) with adjunctive fosfomycin in low-risk/complicated SAB (n = 59), and 15·0% versus 22·8% (RD −7·8% [95% CI −19·9 to 4·3]; p = 0·21) in high-risk/uncomplicated SAB (n = 159); week-8 treatment success was 78·1% versus 88·9% and 61·3% versus 54·4%, respectively. By contrast, in high-risk, complicated SAB (n = 44), adjunctive fosfomycin was associated with higher treatment success (25·8% versus 69·2%; RD −43·4% [−72·9 to −14·0]; p = 0·007) and a non-significant reduction in 60-day mortality (45·2% versus 23·1%). DOOR analysis suggested a more favourable overall outcome profile with adjunctive therapy in this subgroup.</div></div><div><h3>Interpretation</h3><div>Integrating early risk subphenotyping with IDSA complication criteria may enable more precise identification of SAB patients who may benefit from intensified therapy, while supporting monotherapy in those at lowest risk. This stratified approach provides
背景:金黄色葡萄球菌菌血症(SAB)联合治疗的随机试验未能改善临床结果,这可能反映了缺乏针对风险的患者选择。FEN-AUREUS分类能够基于临床亚表型进行早期风险分层。我们的目的是在一项合并试验队列中验证这一框架,并评估将亚表型与idsa定义的复杂SAB结合是否可以识别最有可能从辅助磷霉素中获益的患者。方法:我们对两项多中心随机试验的个体水平数据进行事后分析,以评估磷霉素在SAB中的辅助治疗作用。根据FEN-AUREUS框架将参与者分为表型和风险亚表型。评估亚表型、复杂菌血症和60天死亡率作为主要结局,以及30天死亡率和8周治疗成功作为次要结局之间的关系。DOOR分析提供了对总体结果的综合评估。本研究已在ClinicalTrials.gov注册,编号NCT07155590。结果:在369例患者(中位年龄68岁,IQR为56-78;男性为262/369[68.8%])中,高危亚表型与较高的60天死亡率相关(23.2%对6.6%;风险比[RR] 3.49, 95%可信区间[CI] 1.87 - 6.52;校正风险比[aHR] 3.38, 1.69 - 6.78),与并发症状态无关。将危险亚表型与IDSA分类相结合,发现对辅助磷霉素的反应存在异质性。在低风险、无并发症的SAB患者(n = 107)中,单药治疗和辅助使用磷霉素的60天死亡率都很低(2.1% vs . 3.4%;风险差[RD] - 1.3% [95% CI - 7.4 ~ 4.8]; p = 0.68),第8周的治疗成功率超过89%。在中间阶段,低风险/复杂SAB (n = 59)中,单药组60天死亡率为18.8%,辅助磷霉素组为7.4% (RD为11.3% [95% CI - 5.4至28.1],p = 0.20);高风险/无复杂SAB (n = 159)中,单药组60天死亡率为15.0%,辅助磷霉素组为22.8% (RD为- 7.8% [95% CI - 5.9至4.3],p = 0.21);第8周的治疗成功率分别为78.1%对88.9%和61.3%对54.4%。相比之下,在高风险,复杂的SAB (n = 44)中,辅助磷霉素与更高的治疗成功率相关(25.8%比69.2%;RD - 43.4%[- 72.9至- 14.0];p = 0.007), 60天死亡率无显著降低(45.2%比23.1%)。DOOR分析表明,在该亚组中,辅助治疗的总体结果更有利。解释:将早期风险亚表型与IDSA并发症标准相结合,可以更精确地识别可能受益于强化治疗的SAB患者,同时支持对风险最低的患者进行单药治疗。这种分层的方法提供了一个实用的框架,以完善患者选择,为未来的试验和个性化的治疗策略。资助:西班牙马德里卡洛斯三世研究所。
{"title":"Subphenotype- and complication-guided adjunctive fosfomycin versus standard monotherapy in Staphylococcus aureus bacteraemia: pooled analysis of two randomised trials","authors":"Francesc Escrihuela-Vidal ,&nbsp;Julia García Larrauri ,&nbsp;Joaquín López-Contreras ,&nbsp;Gorane Euba ,&nbsp;Andrea Vázquez ,&nbsp;Silvia Gómez-Zorrilla ,&nbsp;Luis Eduardo López-Cortés ,&nbsp;Oriol Gasch ,&nbsp;Eduardo Aparicio-Minguijón ,&nbsp;Rosa Escudero-Sánchez ,&nbsp;María Teresa Pérez-Rodríguez ,&nbsp;Dolors Rodríguez-Pardo ,&nbsp;Alfredo Jover-Sáenz ,&nbsp;Graciano García-Pardo ,&nbsp;Jesús Rodríguez-Baño ,&nbsp;Miquel Pujol ,&nbsp;Jordi Carratalà ,&nbsp;Belén Gutiérrez-Gutiérrez","doi":"10.1016/j.lanepe.2026.101611","DOIUrl":"10.1016/j.lanepe.2026.101611","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Randomised trials of combination therapies for &lt;em&gt;S. aureus&lt;/em&gt; bacteraemia (SAB) have failed to improve clinical outcomes—likely reflecting the lack of risk-targeted patient selection. The FEN-AUREUS classification enables early risk stratification based on clinical subphenotypes. We aimed to validate this framework in a pooled trial cohort and assess whether combining subphenotypes with IDSA-defined complicated SAB could identify patients most likely to benefit from adjunctive fosfomycin.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We conducted a post-hoc analysis of individual-level data from two multicentre randomised trials evaluating adjunctive fosfomycin in SAB. Participants were classified according to the FEN-AUREUS framework into phenotypes and risk subphenotypes. Associations between subphenotype, complicated bacteraemia, and 60-day mortality as the primary outcome and 30-day mortality and 8-week treatment success as secondary outcomes were assessed. A DOOR analysis provided an integrated assessment of overall outcomes. This study is registered with &lt;span&gt;&lt;span&gt;ClinicalTrials.gov&lt;/span&gt;&lt;svg&gt;&lt;path&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;NCT07155590&lt;/span&gt;&lt;svg&gt;&lt;path&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Findings&lt;/h3&gt;&lt;div&gt;Among 369 patients (median age 68 years, IQR 56–78; 262/369 [68·8%] male), high-risk subphenotypes were associated with greater 60-day mortality (23·2% versus 6·6%; risk ratio [RR] 3·49, 95% confidence interval [CI] 1·87–6·52; adjusted hazard ratio [aHR] 3·38, 1·69–6·78), regardless of complication status. Combining risk subphenotypes with the IDSA classification showed heterogeneity in response to adjunctive fosfomycin. In patients with low-risk and uncomplicated SAB (n = 107), 60-day mortality was low with both monotherapy and adjunctive fosfomycin (2·1% versus 3·4%; risk difference [RD] −1·3% [95% CI −7·4 to 4·8]; p = 0·68), and treatment success at week 8 exceeded 89%. In the intermediate strata, 60-day mortality was 18·8% with monotherapy versus 7·4% (RD 11·3% [95% CI −5·4 to 28·1]; p = 0·20) with adjunctive fosfomycin in low-risk/complicated SAB (n = 59), and 15·0% versus 22·8% (RD −7·8% [95% CI −19·9 to 4·3]; p = 0·21) in high-risk/uncomplicated SAB (n = 159); week-8 treatment success was 78·1% versus 88·9% and 61·3% versus 54·4%, respectively. By contrast, in high-risk, complicated SAB (n = 44), adjunctive fosfomycin was associated with higher treatment success (25·8% versus 69·2%; RD −43·4% [−72·9 to −14·0]; p = 0·007) and a non-significant reduction in 60-day mortality (45·2% versus 23·1%). DOOR analysis suggested a more favourable overall outcome profile with adjunctive therapy in this subgroup.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Interpretation&lt;/h3&gt;&lt;div&gt;Integrating early risk subphenotyping with IDSA complication criteria may enable more precise identification of SAB patients who may benefit from intensified therapy, while supporting monotherapy in those at lowest risk. This stratified approach provides","PeriodicalId":53223,"journal":{"name":"Lancet Regional Health-Europe","volume":"62 ","pages":"Article 101611"},"PeriodicalIF":13.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147367181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Anterior cruciate ligament reconstruction combined with anterolateral ligament reconstruction using hamstring autograft versus anterior cruciate ligament reconstruction using bone–patellar tendon–bone autograft: a randomised controlled trial with 5-year follow-up 前交叉韧带重建联合前外侧韧带重建采用腘绳肌腱自体移植物与前交叉韧带重建采用骨-髌腱-骨自体移植物:一项5年随访的随机对照试验
IF 13 Q1 HEALTH CARE SCIENCES & SERVICES Pub Date : 2026-03-01 Epub Date: 2025-12-20 DOI: 10.1016/j.lanepe.2025.101561
Bertrand Sonnery-Cottet , Alessandro Carrozzo , Hervé Poilvache , Jean-Marie Fayard , Benjamin Freychet , Mathieu Thaunat , Thais Dutra Vieira , Adnan Saithna

Background

Anterior Cruciate Ligament (ACL) rupture is common knee injury. Although ACL reconstruction (ACLR) is standard, graft failure rates remain high in young active patients. This study investigated whether combining ACLR with anterolateral ligament (ALL) reconstruction (ALLR) reduces grafts failure compared with ACLR.

Methods

In this prospective, single-centre, randomised controlled trial conducted at the Santy Orthopedic Center in Lyon, France, patients aged 18–35 years with symptomatic ACL rupture were randomly allocated (1:1) to ACL + ALL reconstruction using hamstring tendon autograft (ACLR + ALLR) or ACLR with bone-patellar tendon-bone autograft (ACLR). Randomisation was performed with a block size of four using telematic software by an independent study coordinator, with concealed allocation. Surgeons were informed of the assigned procedure on the morning of surgery. Outcome assessors were not blinded. The primary outcome was graft failure at 5 years, assessed clinically and by magnetic resonance imaging (MRI) by an independent sports medicine physicians not involved in the index surgery. Efficacy analyses were performed on the Full Analysis Set in accordance with the intention-to-treat principle, while safety analyses were conducted on the Safety Set. Trial registration: ClinicalTrials.gov, ID NCT03740022. The trial has been completed.

Findings

Between November 11, 2016, and January 20, 2020, 593 patients were randomized (297 assigned to ACLR + ALLR and 296 to ACLR). The mean age was 25.0 years (SD 4.5); 447 (75%) participants were male and 146 (25%) female. Of these 593 patients, 556 (94%) completed a mean 5-year follow-up. Graft failure occurred in 12/283 (4.2%) with ACLR + ALLR versus 28/273 (10.3%) with ACLR (p = 0.006; adjusted odds ratio 2.54 [95% CI 1.27; 5.36]—p = 0.008). The number needed to treat was 17 overall, and 9 in patients younger than 25 years.

Interpretation

In our study of young, active adults with ACL rupture, who are considered high-risk for graft failure, combining ACL reconstruction with anterolateral ligament reconstruction (ACLR + ALLR) significantly decreased graft failure compared with ACLR. These results suggest that ACLR + ALLR might be beneficial for young or highly active individuals and provide a basis for future research to refine patient selection, evaluate long-term outcomes beyond five years, and explore benefits in other subgroups of patients with ACL injuries.

Funding

GCS Ramsay Santé pour l'Enseignement et la Recherche funds the scientific activity at the Santy center.
前交叉韧带(ACL)断裂是常见的膝关节损伤。虽然前交叉韧带重建(ACLR)是标准的,但在年轻的活跃患者中移植物失败率仍然很高。本研究探讨与ACLR相比,ACLR联合前外侧韧带(ALL)重建(ALLR)是否能减少移植物衰竭。方法在法国里昂的Santy骨科中心进行的这项前瞻性、单中心、随机对照试验中,年龄在18-35岁的有症状的ACL断裂患者被随机分配(1:1)到ACL + ALL重建使用腘绳肌腱自体移植物(ACLR + ALLR)或ACLR结合骨-髌骨肌腱-骨自体移植物(ACLR)。随机分组由独立研究协调员使用远程信息处理软件进行,分组大小为4个,并进行隐蔽分配。外科医生在手术当天早上被告知指定的手术程序。结果评估者没有采用盲法。主要结果是5年时移植物失败,由独立的运动医学医生通过临床和磁共振成像(MRI)评估,该医生没有参与指数手术。根据意向治疗原则对全分析集进行疗效分析,对安全集进行安全性分析。试验注册:ClinicalTrials.gov,编号NCT03740022。审判已经结束。在2016年11月11日至2020年1月20日期间,593例患者被随机分配(297例分配到ACLR + ALLR, 296例分配到ACLR)。平均年龄25.0岁(SD 4.5);447名(75%)参与者为男性,146名(25%)参与者为女性。在这593例患者中,556例(94%)完成了平均5年的随访。ACLR + ALLR组的移植失败发生率为12/283(4.2%),而ACLR组的移植失败发生率为28/273 (10.3%)(p = 0.006;校正优势比2.54 [95% CI 1.27; 5.36] -p = 0.008)。需要治疗的总人数为17人,25岁以下的患者为9人。在我们的研究中,年轻、活跃的成年ACL破裂患者被认为是移植物失败的高危人群,与ACLR相比,ACL重建联合前外侧韧带重建(ACLR + ALLR)可显著减少移植物失败。这些结果表明,ACLR + ALLR可能对年轻或高度活跃的个体有益,并为未来的研究提供基础,以完善患者选择,评估5年以上的长期结果,并探索其他亚组ACL损伤患者的益处。gcs Ramsay sant pour l’enseignement et la Recherche为圣中心的科学活动提供资金。
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引用次数: 0
30-day postoperative mortality and the effects of hospital preparedness during the COVID-19 pandemic: a pooled analysis of prospective international cohort studies COVID-19大流行期间30天术后死亡率和医院防范措施的影响:前瞻性国际队列研究的汇总分析
IF 13 Q1 HEALTH CARE SCIENCES & SERVICES Pub Date : 2026-03-01 Epub Date: 2026-01-29 DOI: 10.1016/j.lanepe.2025.101566

Background

Surgical services were poorly prepared for the COVID-19 pandemic, leading to widescale disruption to elective activity. This study aimed to identify actionable priorities to strengthen pandemic preparedness of surgical and hospital systems.

Methods

This study pooled data from three international, prospective cohort studies including patients who had a positive SARS-CoV-2 test result in the seven days before or within 30 days after surgery. Patients were included across four pandemic time periods: Period 1 (January–May 2020), Period 2 (June–July 2020), Period 3 (October 2020), and Period 4 (December–March 2022). The primary outcome measure was 30-day postoperative mortality. Hierarchical logistic regression models were developed to explore association between pandemic periods (primary analysis) and hospital-level preparedness (secondary analysis) on 30-day postoperative mortality. Hospital preparedness was classified in to poorly-, moderately-, and highly-prepared tertiles based on Surgical Preparedness Index (SPI) score.

Findings

A total of 31,751 patients were included from 1589 hospitals and 102 countries. From Period 1 through to Period 4 there was a decrease in the proportion of patients aged ≥70 years and with ASA grades 3–5.30-day postoperative mortality fell from Period 1 (18.4% [1378/7502]), Period 2 (9.9% [219/2234], adjusted odds ratio (aOR) 0.65, 95% confidence interval (CI) 0.53–0.78), Period 3 (10.5% [246/2427], aOR 0.60, 95% CI 0.50–0.71), through to Period 4 (5.8% [1132/19,588], aOR 0.33, 95% CI 0.30–0.37). During Period 4, SARS-CoV-2 vaccinated patients had lower mortality compared to unvaccinated patients (4.9% [603/12,361] versus 7.4% [529/7178], aOR 0.49, 95% CI 0.42–0.57). Compared to poorly-prepared hospitals (11.2% [1019/9071]), moderately-prepared (9.4% [857/9071], aOR 0.84, 95% CI 0.75–0.94) and highly-prepared hospitals (5.8% [530/9071], aOR 0.70, 95% CI 0.62–0.80) had lower mortality.

Interpretation

Postoperative mortality decreased over the course of the COVID-19 pandemic and was lower in better prepared hospitals. Hospitals are critical national infrastructure and strengthening their preparedness by developing formal pandemic plans, establishing patient and procedure prioritisation protocols, and ring-fencing surgical beds would ensure safer surgical care during future pandemics.

Funding

National Institute for Health and Care Research, United Kingdom.
外科服务部门对COVID-19大流行准备不足,导致选择性活动大面积中断。本研究旨在确定可采取行动的优先事项,以加强外科和医院系统的大流行防范。方法本研究汇集了三项国际前瞻性队列研究的数据,这些研究包括术前7天或术后30天内SARS-CoV-2检测结果阳性的患者。患者被纳入四个大流行时期:第一阶段(2020年1月至5月)、第二阶段(2020年6月至7月)、第三阶段(2020年10月)和第四阶段(2022年12月至3月)。主要结局指标为术后30天死亡率。建立了层次逻辑回归模型,探讨大流行时期(初级分析)和医院层面的防范(二级分析)与术后30天死亡率之间的关系。根据手术准备指数(SPI)评分,将医院准备分为低准备、中等准备和高度准备。来自102个国家1589家医院的31751名患者被纳入研究。从第1期到第4期,年龄≥70岁、ASA等级为3 - 5.30天的患者术后死亡率从第1期(18.4%[1378/7502])、第2期(9.9%[219/2234],调整优势比(aOR) 0.65, 95%可信区间(CI) 0.53-0.78)、第3期(10.5% [246/2427],aOR 0.60, 95% CI 0.50-0.71)到第4期(5.8% [1132/ 19588],aOR 0.33, 95% CI 0.30-0.37)下降。在第4期,接种SARS-CoV-2疫苗的患者死亡率低于未接种疫苗的患者(4.9%[603/12,361]对7.4% [529/7178],aOR 0.49, 95% CI 0.42-0.57)。与准备不足的医院(11.2%[1019/9071])相比,准备适度的医院(9.4% [857/9071],aOR 0.84, 95% CI 0.75 ~ 0.94)和准备充分的医院(5.8% [5.3 /9071],aOR 0.70, 95% CI 0.62 ~ 0.80)的死亡率较低。在COVID-19大流行期间,术后死亡率有所下降,在准备较好的医院中死亡率更低。医院是至关重要的国家基础设施,通过制定正式的大流行计划、建立病人和手术优先次序协议以及围篱手术床来加强医院的防范,将确保在未来大流行期间更安全的手术护理。英国国家卫生和保健研究所。
{"title":"30-day postoperative mortality and the effects of hospital preparedness during the COVID-19 pandemic: a pooled analysis of prospective international cohort studies","authors":"","doi":"10.1016/j.lanepe.2025.101566","DOIUrl":"10.1016/j.lanepe.2025.101566","url":null,"abstract":"<div><h3>Background</h3><div>Surgical services were poorly prepared for the COVID-19 pandemic, leading to widescale disruption to elective activity. This study aimed to identify actionable priorities to strengthen pandemic preparedness of surgical and hospital systems.</div></div><div><h3>Methods</h3><div>This study pooled data from three international, prospective cohort studies including patients who had a positive SARS-CoV-2 test result in the seven days before or within 30 days after surgery. Patients were included across four pandemic time periods: Period 1 (January–May 2020), Period 2 (June–July 2020), Period 3 (October 2020), and Period 4 (December–March 2022). The primary outcome measure was 30-day postoperative mortality. Hierarchical logistic regression models were developed to explore association between pandemic periods (primary analysis) and hospital-level preparedness (secondary analysis) on 30-day postoperative mortality. Hospital preparedness was classified in to poorly-, moderately-, and highly-prepared tertiles based on Surgical Preparedness Index (SPI) score.</div></div><div><h3>Findings</h3><div>A total of 31,751 patients were included from 1589 hospitals and 102 countries. From Period 1 through to Period 4 there was a decrease in the proportion of patients aged ≥70 years and with ASA grades 3–5.30-day postoperative mortality fell from Period 1 (18.4% [1378/7502]), Period 2 (9.9% [219/2234], adjusted odds ratio (aOR) 0.65, 95% confidence interval (CI) 0.53–0.78), Period 3 (10.5% [246/2427], aOR 0.60, 95% CI 0.50–0.71), through to Period 4 (5.8% [1132/19,588], aOR 0.33, 95% CI 0.30–0.37). During Period 4, SARS-CoV-2 vaccinated patients had lower mortality compared to unvaccinated patients (4.9% [603/12,361] versus 7.4% [529/7178], aOR 0.49, 95% CI 0.42–0.57). Compared to poorly-prepared hospitals (11.2% [1019/9071]), moderately-prepared (9.4% [857/9071], aOR 0.84, 95% CI 0.75–0.94) and highly-prepared hospitals (5.8% [530/9071], aOR 0.70, 95% CI 0.62–0.80) had lower mortality.</div></div><div><h3>Interpretation</h3><div>Postoperative mortality decreased over the course of the COVID-19 pandemic and was lower in better prepared hospitals. Hospitals are critical national infrastructure and strengthening their preparedness by developing formal pandemic plans, establishing patient and procedure prioritisation protocols, and ring-fencing surgical beds would ensure safer surgical care during future pandemics.</div></div><div><h3>Funding</h3><div><span>National Institute for Health and Care Research</span>, United Kingdom.</div></div>","PeriodicalId":53223,"journal":{"name":"Lancet Regional Health-Europe","volume":"62 ","pages":"Article 101566"},"PeriodicalIF":13.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Breast cancer incidence, by stage at diagnosis, and mortality in 21 European countries in the era of mammography screening: an international population-based study 在乳房x线摄影筛查时代,21个欧洲国家按诊断阶段划分的乳腺癌发病率和死亡率:一项基于国际人群的研究
IF 13 Q1 HEALTH CARE SCIENCES & SERVICES Pub Date : 2026-03-01 Epub Date: 2025-12-29 DOI: 10.1016/j.lanepe.2025.101574
Rafael Cardoso , Idris Ola , Lina Jansen , Monika Hackl , Petra Ihle , Julie Francart , Nancy Van Damme , Zdravka Valerianova , Trayan Atanasov , Ondřej Májek , Ondřej Ngo , Kaire Innos , Margit Mägi , Sandrine Dabakuyo Yonli , Anne-Sophie Woronoff , Brigitte Tretarre , Florence Poncet , Alexander Katalinic , Paul M. Walsh , Ieva Vincerževskienė , Hermann Brenner

Background

Mammography screening programmes have been widely implemented across European countries over the past 40 years with the main aim to detect breast cancer earlier and thereby reduce breast cancer mortality. This study aimed to analyse and compare changes over time in breast cancer incidence, by stage at diagnosis, and breast cancer mortality across countries in relation to the timing of screening implementation and age at diagnosis.

Methods

In this population-based study conducted in 21 European countries, data from cancer registries covering over 3 million female patients diagnosed with breast cancer, along with data from national statistical offices from 1978 to 2019 were analysed. Annual age-standardised breast cancer incidence rates (by stage and age at diagnosis) and age-standardised breast cancer mortality rates were calculated. Average annual percent changes (AAPCs) in these metrics within 10 years before and 10 years after screening implementation were estimated.

Findings

Overall, breast cancer incidence rates increased over the study period, with the largest increases observed in the first two decades (1978–1987 and 1988–1997), and AAPCs of up to 4.55 (95% confidence interval, CI, 2.56–6.57). In contrast, breast cancer mortality rates decreased most predominantly in the last two decades (1998–2007 and 2008–2018/19), with AAPCs down to −5.40 (95% CI, −9.70 to −0.89). The largest increases in incidence were seen for in situ and stage I cancers (AAPCs ranging from non-significant to 12.03 (95% CI, 7.40–16.86) following screening implementation). Incidence of stage IV cancer declined or remained stable in most countries, with AAPCs down to −6.16 (95% CI, −8.28 to −4.00) after screening introduction. These trends were particularly pronounced among age groups targeted by screening (mostly 50–69 years). Breast cancer mortality rates declined by up to 3 percent annually after screening initiation (lowest AAPC estimate −3.29 (95% CI, −6.26 to −0.23); yet, AAPCs as low as −2.54 (95% CI, −3.15 to −1.93) were also observed before introduction of screening programmes in countries where implementation occurred later, in the 2000s.

Interpretation

This study suggests that mammography screening has influenced trends in breast cancer incidence and mortality in European countries. The results point to the contribution of mammography screening, alongside advances in diagnostics and treatment, to the observed reductions in breast cancer mortality.

Funding

There was no funding source for this study.
在过去的40年里,乳房x线摄影筛查项目在欧洲国家广泛实施,主要目的是早期发现乳腺癌,从而降低乳腺癌死亡率。本研究旨在分析和比较各国乳腺癌发病率、诊断阶段和乳腺癌死亡率随时间的变化,这些变化与筛查实施时间和诊断年龄有关。在这项在21个欧洲国家进行的基于人群的研究中,研究人员分析了来自癌症登记处的数据,这些数据涵盖了300多万名被诊断患有乳腺癌的女性患者,以及1978年至2019年各国统计局的数据。计算了年度年龄标准化乳腺癌发病率(按诊断时的分期和年龄划分)和年龄标准化乳腺癌死亡率。这些指标在筛选实施前后10年内的平均年变化百分比(AAPCs)进行了估计。总体而言,乳腺癌发病率在研究期间呈上升趋势,前20年(1978-1987年和1988-1997年)的增幅最大,AAPCs高达4.55(95%可信区间,CI, 2.56-6.57)。相比之下,乳腺癌死亡率在过去二十年(1998-2007年和2008-2018/19年)下降最为显著,aapc降至- 5.40 (95% CI, - 9.70至- 0.89)。原位癌和I期癌的发病率增幅最大(筛查实施后,AAPCs从无显著性到12.03 (95% CI, 7.40-16.86))。在大多数国家,IV期癌症的发病率下降或保持稳定,在引入筛查后,aapc降至- 6.16 (95% CI, - 8.28至- 4.00)。这些趋势在筛查的目标年龄组(主要是50-69岁)中尤为明显。筛查开始后,乳腺癌死亡率每年下降3%(最低AAPC估计值为- 3.29 (95% CI, - 6.26至- 0.23);然而,在21世纪初实施筛查计划较晚的国家,在引入筛查计划之前,aapc也低至- 2.54 (95% CI, - 3.15至- 1.93)。本研究表明,乳房x光检查影响了欧洲国家乳腺癌发病率和死亡率的趋势。研究结果表明,乳房x光检查以及诊断和治疗方面的进步,对观察到的乳腺癌死亡率的降低做出了贡献。本研究没有资金来源。
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引用次数: 0
Efficacy of anakinra in reducing progression to organ dysfunction in patients with pneumonia (INSPIRE): a randomised, double-blind, placebo-controlled, phase IIa trial anakinra减少肺炎患者器官功能障碍进展的疗效(INSPIRE):一项随机、双盲、安慰剂对照的IIa期试验
IF 13 Q1 HEALTH CARE SCIENCES & SERVICES Pub Date : 2026-03-01 Epub Date: 2025-12-29 DOI: 10.1016/j.lanepe.2025.101573
Georgios Tavoulareas , Olga Kontakou-Zoniou , Nikolaos Antonakos , Elisavet Tasouli , George Adamis , Nikolaos Kakavoulis , Evangelos Michelakis , Ilias Skopelitis , Konstantina Dakou , Christos Psarrakis , Panagiotis Koufargyris , Myrto Astriti , Styliani Sympardi , Evangelos J. Giamarellos-Bourboulis

Background

Early recognition of risk of death in pneumonia and start of precision immunotherapy to improve outcomes is an unmet need. We hypothesized that a precision strategy approach combining early recognition of interleukin (IL)-1 activation coupled with Anakinra treatment may improve pneumonia outcome.

Methods

INSPIRE is a prospective, double-blind randomized placebo-controlled trial which recruited hospitalized adults with community-acquired or hospital-acquired pneumonia, with qSOFA (quick sequential organ failure assessment) equal to 1 and plasma presepsin (soluble CD14) more than 350 pg/ml. Patients were 1:1 randomised to standard-of-care medication plus either subcutaneous placebo or subcutaneous Anakinra 100 mg once daily for 10 days. The primary endpoint was progression into organ dysfunction defined as meeting at least one of the following two conditions; (i) at least 2-point increase of the baseline SOFA score by day 7 and/or (ii) death by day 90. This was analyzed in the intention-to-treat (ITT) population. This trial is registered with the EU Clinical Trials Register (2022-002390-28) and ClinicalTrials.gov (NCT05785442).

Findings

Patients were enrolled between March 2023 and June 2024; 30 patients in the placebo arm and 30 patients in the Anakinra arm were the ITT population. The primary endpoint was met in 50·0% (15 patients) of placebo-treated and in 20·0% (6 patients) of Anakinra-treated patients (difference 30·0% [5·9 to 49%]; p: 0·011). 90-day mortality was 43·3% (13 patients) and 20·0% (6 patients) (difference 23·3% [0 to 43·7%]; p: 0·029). The overall incidence of serious treatment-emergent adverse events (TEAEs) in the placebo group was 50% and in the Anakinra group 33·3%. None of the serious TEAEs was judged to be related to treatment assignment. Production of TNFα and ΙFNγ by blood mononuclear cells was decreased.

Interpretation

Presepsin-guided Anakinra treatment prevents progression of pneumonia to organ dysfunction and death. The mechanism of benefit is associated with attenuation of cytokine production.

Funding

Hellenic Institute for the Study of Sepsis; PHC Europe BV; Swedish Orphan Biovitrum AB.
背景:认识到肺炎的死亡风险并开始精确免疫治疗以改善预后是一个尚未满足的需求。我们假设一种精确的策略方法结合早期识别白细胞介素(IL)-1激活加上Anakinra治疗可能改善肺炎的预后。方法sinspire是一项前瞻性、双盲随机安慰剂对照试验,招募qSOFA(快速顺序器官衰竭评估)等于1、血浆前压素(可溶性CD14)大于350pg /ml的社区获得性或医院获得性肺炎住院成人患者。患者按1:1随机分配至标准护理药物加皮下安慰剂或皮下阿那金100 mg,每天一次,持续10天。主要终点是进展为器官功能障碍,定义为满足以下两个条件中的至少一个;(i)到第7天基线SOFA评分至少增加2个点和/或(ii)到第90天死亡。这是在意向治疗(ITT)人群中分析的。该试验已在EU临床试验注册(2022-002390-28)和ClinicalTrials.gov (NCT05785442)注册。患者在2023年3月至2024年6月期间入组;安慰剂组的30名患者和Anakinra组的30名患者是ITT人群。安慰剂治疗组的主要终点达到50.0%(15例),anakinra治疗组的主要终点达到20.0%(6例)(差异30.0% [5.9 ~ 49%];p: 0.011)。90天死亡率分别为43.3%(13例)和20.0%(6例)(差异为23.3% [0 ~ 43.7%];p: 0.029)。安慰剂组的严重治疗不良事件(teae)总发生率为50%,阿那金组为33.3%。没有一个严重的teae被认为与治疗分配有关。血单个核细胞产生TNFα和ΙFNγ减少。presepin引导的Anakinra治疗可预防肺炎进展到器官功能障碍和死亡。其作用机制与抑制细胞因子的产生有关。希腊败血症研究所;PHC Europe BV;瑞典孤儿Biovitrum AB。
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引用次数: 0
Long-term effect of discontinuing anticholinesterase treatment on cognitive decline and mortality in Alzheimer's disease in France: a quasi-experiment and target trial emulation study 停止抗胆碱酯酶治疗对法国阿尔茨海默病认知能力下降和死亡率的长期影响:一项准实验和目标试验模拟研究
IF 13 Q1 HEALTH CARE SCIENCES & SERVICES Pub Date : 2026-03-01 Epub Date: 2026-02-12 DOI: 10.1016/j.lanepe.2026.101607
Simon Lecerf , Octave Guinebretiere , Raphaël Bentegeac , Victoria Gauthier , Estelle Aymes , Chaymae Mekkaoui , Julien Dumurgier , Philippe Amouyel , Stanley Durrleman , Thomas Nedelec , Thibaud Lebouvier

Background

In 2018, France withdrew reimbursement for cholinesterase inhibitors (ChEIs) in Alzheimer's disease, citing modest efficacy, lack of long-term benefit, and safety concerns. This policy shift provided a unique opportunity to assess ChEI effectiveness in real-world settings, by evaluating, among patients treated with ChEI between 01/08/2017 and 01/08/2018, the impact of treatment discontinuation on cognitive decline (MMSE score) and survival.

Methods

Using the French National Alzheimer's Database (BNA) and Meotis databases, we emulated a pragmatic, intention-to-treat trial comparing patients who discontinued ChEIs after delisting to those who continued treatment, under quasi-experimental conditions. To model cognitive trajectories, we used the inverse probability treatment-weighted (IPTW) cohort and applied mixed-effects models with random intercepts across all follow-up visits. Survival was estimated with a pooled logistic regression including treatment group, follow-up time, and an interaction between treatment and time.

Findings

The mean difference in MMSE decline between discontinuers and continuers after one year was 0·97 points (95% CI 0·68–1·27, p < 0·001), reaching 1·81 points (0·91–2·71, p < 0·001), after four years. No significant difference in mortality (RR 1·10, 95% CI [0·95–1·29]) was observed over a five-year period.

Interpretation

Our findings confirm and extend prior trials by demonstrating the sustained cognitive benefits of ChEIs in a real-world setting. While acknowledging the limitations associated with its retrospective nature, our study argues for reconsidering the 2018 delisting decision, as ChEIs remain safe and clinically relevant for mild-to-moderate Alzheimer's disease.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
2018年,法国撤销了针对阿尔茨海默病的胆碱酯酶抑制剂(ChEIs)的报销,理由是疗效一般、缺乏长期获益和安全性问题。这一政策转变提供了一个独特的机会,通过评估在2017年8月1日至2018年8月1日期间接受ChEI治疗的患者中,停止治疗对认知能力下降(MMSE评分)和生存的影响,来评估现实环境中ChEI的有效性。方法利用法国国家阿尔茨海默病数据库(BNA)和Meotis数据库,在准实验条件下,我们模拟了一项实用的意向治疗试验,比较了在退市后停用ChEIs的患者和继续治疗的患者。为了模拟认知轨迹,我们使用了逆概率治疗加权(IPTW)队列,并在所有随访中采用随机截距的混合效应模型。生存率通过合并逻辑回归估计,包括治疗组、随访时间以及治疗和时间之间的相互作用。结果:停止治疗与继续治疗一年后MMSE下降的平均差异为0.97点(95% CI 0.68 ~ 1.27, p < 0.001),四年后达到1.81点(0.91 ~ 1.71,p < 0.001)。5年期间死亡率无显著差异(RR为1.10,95% CI[0.95 - 0.29])。解释:我们的研究结果证实并扩展了之前的试验,证明了chei在现实世界中持续的认知益处。在承认其回顾性的局限性的同时,我们的研究主张重新考虑2018年的退市决定,因为chei仍然是安全的,并且与轻度至中度阿尔茨海默病具有临床相关性。本研究未获得任何公共、商业或非营利部门的资助机构的特别资助。
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Lancet Regional Health-Europe
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