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Using UK Biobank data to establish population-specific atlases from whole body MRI. 利用英国生物库数据,从全身核磁共振成像中建立特定人群图谱。
IF 5.4 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-11-19 DOI: 10.1038/s43856-024-00670-0
Sophie Starck, Vasiliki Sideri-Lampretsa, Jessica J M Ritter, Veronika A Zimmer, Rickmer Braren, Tamara T Mueller, Daniel Rueckert

Background: Reliable reference data in medical imaging is largely unavailable. Developing tools that allow for the comparison of individual patient data to reference data has a high potential to improve diagnostic imaging. Population atlases are a commonly used tool in medical imaging to facilitate this. Constructing such atlases becomes particularly challenging when working with highly heterogeneous datasets, such as whole-body images, which contain significant anatomical variations.

Method: In this work, we propose a pipeline for generating a standardised whole-body atlas for a highly heterogeneous population by partitioning the population into anatomically meaningful subgroups. Using magnetic resonance images from the UK Biobank dataset, we create six whole-body atlases representing a healthy population average. We furthermore unbias them, and this way obtain a realistic representation of the population. In addition to the anatomical atlases, we generate probabilistic atlases that capture the distributions of abdominal fat (visceral and subcutaneous) and five abdominal organs across the population (liver, spleen, pancreas, left and right kidneys).

Results: Our pipeline effectively generates high-quality, realistic whole-body atlases with clinical applicability. The probabilistic atlases show differences in fat distribution between subjects with medical conditions such as diabetes and cardiovascular diseases and healthy subjects in the atlas space.

Conclusions: With this work, we make the constructed anatomical and label atlases publically available, with the expectation that they will support medical research involving whole-body MR images.

背景:医学成像中可靠的参考数据在很大程度上是不可用的。开发可将单个患者数据与参考数据进行比较的工具极有可能改进影像诊断。人群图谱是医学影像中常用的工具,可促进这一工作。在处理高度异构的数据集时,构建这样的图集尤其具有挑战性,例如包含显著解剖学差异的全身图像:在这项工作中,我们提出了一个管道,通过将人群划分为具有解剖意义的亚组,为高度异构的人群生成标准化的全身图集。利用英国生物库数据集的磁共振图像,我们创建了代表健康人群平均水平的六个全身图谱。此外,我们还对它们进行了不偏倚处理,从而获得了一个真实的人群代表。除了解剖图集外,我们还生成了概率图集,以捕捉整个人群的腹部脂肪(内脏和皮下脂肪)和五个腹部器官(肝脏、脾脏、胰腺、左肾和右肾)的分布情况:结果:我们的管道能有效生成高质量、逼真的全身图谱,具有临床应用价值。概率图集显示了患有糖尿病和心血管疾病等疾病的受试者与健康受试者在图集空间的脂肪分布差异:通过这项工作,我们公开了所构建的解剖和标签图谱,希望它们能为涉及全身磁共振图像的医学研究提供支持。
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引用次数: 0
Ursodeoxycholic acid and severe COVID-19 outcomes in a cohort study using the OpenSAFELY platform. 使用 OpenSAFELY 平台进行的队列研究中的熊去氧胆酸和严重 COVID-19 结果。
IF 5.4 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-11-19 DOI: 10.1038/s43856-024-00664-y
Ruth E Costello, Karen M J Waller, Rachel Smith, George F Mells, Angel Y S Wong, Anna Schultze, Viyaasan Mahalingasivam, Emily Herrett, Bang Zheng, Liang-Yu Lin, Brian MacKenna, Amir Mehrkar, Sebastian C J Bacon, Ben Goldacre, Laurie A Tomlinson, John Tazare, Christopher T Rentsch

Background: Biological evidence suggests ursodeoxycholic acid (UDCA)-a common treatment of cholestatic liver disease-may prevent severe COVID-19 outcomes. We aimed to compare the hazard of COVID-19 hospitalisation or death between UDCA users versus non-users in a population with primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC).

Methods: With the approval of NHS England, we conducted a population-based cohort study using primary care records between 1 March 2020 and 31 December 2022, linked to death registration data and hospital records through the OpenSAFELY-TPP platform. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between time-varying UDCA exposure and COVID-19 related hospitalisation or death, stratified by geographical region and considering models unadjusted and fully adjusted for pre-specified confounders.

Results: We identify 11,305 eligible individuals, 640 were hospitalised or died with COVID-19 during follow-up, 400 (63%) events among UDCA users. After confounder adjustment, UDCA is associated with a 21% relative reduction in the hazard of COVID-19 hospitalisation or death (HR 0.79, 95% CI 0.67-0.93), consistent with an absolute risk reduction of 1.35% (95% CI 1.07%-1.69%).

Conclusions: We found evidence that UDCA is associated with a lower hazard of COVID-19 related hospitalisation and death, support calls for clinical trials investigating UDCA as a preventative measure for severe COVID-19 outcomes.

背景:生物学证据表明,熊去氧胆酸(UDCA)--胆汁淤积性肝病的一种常见治疗方法--可预防严重的 COVID-19 结果。我们旨在比较原发性胆汁性胆管炎(PBC)或原发性硬化性胆管炎(PSC)人群中使用 UDCA 与不使用 UDCA 者 COVID-19 住院或死亡的风险:经英格兰国家医疗服务体系(NHS)批准,我们利用 2020 年 3 月 1 日至 2022 年 12 月 31 日期间的初级保健记录开展了一项基于人群的队列研究,并通过 OpenSAFELY-TPP 平台将这些记录与死亡登记数据和医院记录连接起来。研究采用 Cox 比例危险度回归法估算随时间变化的 UDCA 暴露与 COVID-19 相关住院或死亡之间的危险度比 (HR) 和 95% 置信区间 (CI),按地理区域进行分层,并考虑未调整和完全调整预设混杂因素的模型:我们确定了11305名符合条件的患者,其中640人在随访期间因COVID-19住院或死亡,400人(63%)为UDCA使用者。经混杂因素调整后,UDCA可使COVID-19住院或死亡风险相对降低21%(HR 0.79,95% CI 0.67-0.93),绝对风险降低1.35%(95% CI 1.07%-1.69%):我们发现有证据表明,UDCA 与 COVID-19 相关的住院和死亡风险较低,这支持了将 UDCA 作为严重 COVID-19 结果预防措施进行临床试验的呼吁。
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引用次数: 0
Predicting individual patient and hospital-level discharge using machine learning. 利用机器学习预测患者个人和医院层面的出院情况。
IF 5.4 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-11-18 DOI: 10.1038/s43856-024-00673-x
Jia Wei, Jiandong Zhou, Zizheng Zhang, Kevin Yuan, Qingze Gu, Augustine Luk, Andrew J Brent, David A Clifton, A Sarah Walker, David W Eyre

Background: Accurately predicting hospital discharge events could help improve patient flow and the efficiency of healthcare delivery. However, using machine learning and diverse electronic health record (EHR) data for this task remains incompletely explored.

Methods: We used EHR data from February-2017 to January-2020 from Oxfordshire, UK to predict hospital discharges in the next 24 h. We fitted separate extreme gradient boosting models for elective and emergency admissions, trained on the first two years of data and tested on the final year of data. We examined individual-level and hospital-level model performance and evaluated the impact of training data size and recency, prediction time, and performance in subgroups.

Results: Our models achieve AUROCs of 0.87 and 0.86, AUPRCs of 0.66 and 0.64, and F1 scores of 0.61 and 0.59 for elective and emergency admissions, respectively. These models outperform a logistic regression model using the same features and are substantially better than a baseline logistic regression model with more limited features. Notably, the relative performance increase from adding additional features is greater than the increase from using a sophisticated model. Aggregating individual probabilities, daily total discharge estimates are accurate with mean absolute errors of 8.9% (elective) and 4.9% (emergency). The most informative predictors include antibiotic prescriptions, medications, and hospital capacity factors. Performance remains robust across patient subgroups and different training strategies, but is lower in patients with longer admissions and those who died in hospital.

Conclusions: Our findings highlight the potential of machine learning in optimising hospital patient flow and facilitating patient care and recovery.

背景:准确预测出院事件有助于改善患者流程和提高医疗服务效率。然而,利用机器学习和多样化的电子健康记录(EHR)数据来完成这项任务的探索仍未完成:我们使用了英国牛津郡 2017 年 2 月至 2020 年 1 月的电子病历数据来预测未来 24 小时内的出院情况。我们为择期入院和急诊入院分别拟合了极端梯度提升模型,在前两年的数据上进行了训练,并在最后一年的数据上进行了测试。我们检查了个人层面和医院层面的模型性能,并评估了训练数据大小和重复性、预测时间以及分组性能的影响:我们的模型在择期入院和急诊入院方面的 AUROC 分别为 0.87 和 0.86,AUPRC 分别为 0.66 和 0.64,F1 分别为 0.61 和 0.59。这些模型优于使用相同特征的逻辑回归模型,也大大优于使用更有限特征的基线逻辑回归模型。值得注意的是,增加额外特征所带来的相对性能提升要大于使用复杂模型所带来的提升。汇总单个概率后,每日总出院率估计值准确,平均绝对误差为 8.9%(择期)和 4.9%(急诊)。最有参考价值的预测因素包括抗生素处方、药物和医院容量因素。在不同的患者亚群和不同的训练策略下,预测结果仍然保持稳定,但在入院时间较长的患者和在医院死亡的患者中,预测结果较低:我们的研究结果凸显了机器学习在优化医院患者流程、促进患者护理和康复方面的潜力。
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引用次数: 0
Restoring brain connectivity by phrenic nerve stimulation in sedated and mechanically ventilated patients. 通过刺激膈神经恢复镇静和机械通气患者的大脑连接。
IF 5.4 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-11-18 DOI: 10.1038/s43856-024-00662-0
Thiago Bassi, Elizabeth Rohrs E, Melodie Parfait, Brett C Hannigan, Steven Reynolds, Julien Mayaux, Maxens Decavèle, Jose Herrero, Alexandre Demoule, Thomas Similowski, Martin Dres

Background: In critically ill patients, deep sedation and mechanical ventilation suppress the brain-diaphragm-lung axis and are associated with cognitive issues in survivors.

Methods: This exploratory crossover design study investigates whether phrenic nerve stimulation can enhance brain activity and connectivity in six deeply sedated, mechanically ventilated patients with acute respiratory distress syndrome.

Results: Our findings indicate that adding phrenic stimulation on top of invasive mechanical ventilation in deeply sedated, critically ill, moderate acute respiratory distress syndrome patients increases cortical activity, connectivity, and synchronization in the frontal-temporal-parietal cortices.

Conclusions: Adding phrenic stimulation on top of invasive mechanical ventilation in deeply sedated, critically ill, moderate acute respiratory distress syndrome patients increases cortical activity, connectivity, and synchronization. The observed changes resemble those during diaphragmatic breathing in awake humans. These results suggest that phrenic nerve stimulation has the potential to restore the brain-diaphragm-lung crosstalk when it has been shut down or impaired by mechanical ventilation and sedation. Further research should evaluate the clinical significance of these results.

背景:在重症患者中,深度镇静和机械通气会抑制脑-膈-肺轴,并与幸存者的认知问题有关:在重症患者中,深度镇静和机械通气会抑制脑-膈-肺轴,并与幸存者的认知问题有关:这项探索性交叉设计研究调查了膈神经刺激是否能增强六名深度镇静、机械通气的急性呼吸窘迫综合征患者的大脑活动和连通性:我们的研究结果表明,在对深度镇静、重症、中度急性呼吸窘迫综合征患者进行有创机械通气的基础上进行膈神经刺激,可以增强大脑皮层的活动、连通性以及额颞顶叶皮层的同步性:在对深度镇静的中度急性呼吸窘迫综合征重症患者进行有创机械通气的基础上增加膈肌刺激,可增加大脑皮层的活动、连通性和同步性。观察到的变化类似于清醒状态下人类横膈膜呼吸时的变化。这些结果表明,当大脑-膈肌-肺的串联因机械通气和镇静而关闭或受损时,刺激膈神经有可能恢复这种串联。进一步的研究应评估这些结果的临床意义。
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引用次数: 0
Multiomics biomarkers were not superior to clinical variables for pan-cancer screening 在泛癌症筛查中,多组学生物标记物并不优于临床变量
IF 5.4 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-11-17 DOI: 10.1038/s43856-024-00671-z
Martin Smelik, Yelin Zhao, Dina Mansour Aly, AKM Firoj Mahmud, Oleg Sysoev, Xinxiu Li, Mikael Benson
Cancer screening tests are considered pivotal for early diagnosis and survival. However, the efficacy of these tests for improving survival has recently been questioned. This study aims to test if cancer screening could be improved by biomarkers in peripheral blood based on multi-omics data. We utilize multi-omics data from 500,000 participants in the UK Biobank. Machine learning is applied to search for proteins, metabolites, genetic variants, or clinical variables to diagnose cancers collectively and individually. Here we show that the overall performance of the potential blood biomarkers do not outperform clinical variables for collective diagnosis. However, we observe promising results for individual cancers in close proximity to peripheral blood, with an Area Under the Curve (AUC) greater than 0.8. Our findings suggest that the identification of blood biomarkers for cancer might be complicated by variable overlap between molecular changes in tumor tissues and peripheral blood. This explanation is supported by local proteomics analyses of different tumors, which all show high AUCs, greater than 0.9. Thus, multi-omics biomarkers for the diagnosis of individual cancers may potentially be effective, but not for groups of cancers. This study aimed to find out if we could improve cancer screening tests by looking for signs of cancer in blood samples. We used computer and mathematical models to analyze data from 500,000 people. We found that these blood tests were not better than existing methods for diagnosing multiple types of cancer at once. However, they did show promise for diagnosing individual types of cancer that are close to the bloodstream. This suggests that finding blood markers for cancer is complex and depends on how much the cancer affects the blood. These findings could help in the development of more effective tests for individual types of cancer in the future. Smelik et al. investigate the effectiveness of using multi-omics biomarkers in blood for cancer screening. The results indicate that while these biomarkers show promise for diagnosing individual cancers in close proximity to the blood stream, they do not surpass clinical variables for diagnosing multiple cancers.
癌症筛查测试被认为是早期诊断和生存的关键。然而,这些检测对提高生存率的功效最近受到了质疑。本研究旨在基于多组学数据,检验外周血中的生物标记物是否能改善癌症筛查。我们利用了英国生物库中 50 万名参与者的多组学数据。应用机器学习搜索蛋白质、代谢物、遗传变异或临床变量,以诊断癌症的集体和个体。我们在此表明,在集体诊断方面,潜在血液生物标记物的整体表现并不优于临床变量。不过,我们观察到,对于与外周血关系密切的单个癌症,结果很有希望,曲线下面积(AUC)大于 0.8。我们的研究结果表明,由于肿瘤组织和外周血分子变化之间存在不同程度的重叠,癌症血液生物标记物的鉴定可能会变得复杂。对不同肿瘤进行的局部蛋白质组学分析也支持这一解释,这些分析均显示出大于 0.9 的高 AUC。因此,多组学生物标志物对单个癌症的诊断可能有效,但对癌症组的诊断则无效。这项研究的目的是了解我们能否通过在血液样本中寻找癌症迹象来改进癌症筛查测试。我们使用计算机和数学模型分析了 50 万人的数据。我们发现,在一次性诊断多种类型的癌症方面,这些血液检测并不比现有方法更好。不过,它们确实有望诊断出接近血液的个别癌症类型。这表明,寻找癌症的血液标记非常复杂,取决于癌症对血液的影响程度。这些发现可能有助于将来针对个别类型的癌症开发出更有效的检测方法。Smelik 等人研究了使用血液中的多组学生物标记物进行癌症筛查的有效性。结果表明,虽然这些生物标志物在诊断与血流接近的个别癌症方面显示出前景,但它们在诊断多种癌症方面并没有超过临床变量。
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引用次数: 0
Discriminating Parkinson’s disease patients from healthy controls using nasal respiratory airflow 利用鼻腔呼吸气流区分帕金森病患者和健康对照组
IF 5.4 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-11-14 DOI: 10.1038/s43856-024-00660-2
Michal Andelman-Gur, Kobi Snitz, Danielle Honigstein, Aharon Weissbrod, Timna Soroka, Aharon Ravia, Lior Gorodisky, Liron Pinchover, Adi Ezra, Neomi Hezi, Tanya Gurevich, Noam Sobel
Breathing patterns may inform on health. We note that the sites of earliest brain damage in Parkinson’s disease (PD) house the neural pace-makers of respiration. We therefore hypothesized that ongoing long-term temporal dynamics of respiration may be altered in PD. We applied a wearable device that precisely logs nasal airflow over time in 28 PD patients (mostly H&Y stage-II) and 33 matched healthy controls. Each participant wore the device for 24 h of otherwise routine daily living. We observe significantly altered temporal patterns of nasal airflow in PD, where inhalations are longer and less variable than in matched controls (mean PD = −1.22 ± 1.9 (combined respiratory features score), Control = 1.04 ± 2.16, Wilcoxon rank-sum test, z = −4.1, effect size Cliff’s δ = −0.61, 95% confidence interval = −0.79 – (−0.34), P = 4.3 × 10−5). The extent of alteration is such that using only 30 min of recording we detect PD at 87% accuracy (AUC = 0.85, 79% sensitivity (22 of 28), 94% specificity (31 of 33), z = 5.7, p = 3.5 × 10−9), and also predict disease severity (correlation with UPDRS-Total score: r = 0.49; P = 0.008). We conclude that breathing patterns are altered by H&Y stage-II in the disease cascade, and our methods may be further refined in the future to provide an indication with diagnostic and prognostic value. Andelman-Gur et al. use a nasal airflow monitoring device to detect alterations of respiratory dynamics in patients with Parkinson’s Disease. They reveal longer, but less variable, inhalations and show that changes in airflow dynamics are correlated with disease severity, plus 30 min of data is adequate to discriminate patients from controls. In its earliest stages, Parkinson’s disease damages the parts of the brain that control breathing. We built a small device that measures airflow patterns through the nose over time. People with Parkinson’s disease and healthy individuals wore this device for 24 h. We found that nasal inhalations in Parkinson’s patients were longer and less variable than in healthy individuals. This difference was so pronounced that, using only 30 min of recording, we could accurately determine most people who had Parkinson’s disease and how severe their disease was. Future studies will determine whether this tool can contribute to early diagnosis, and it may be useful to monitor disease progression.
背景:呼吸模式可为健康提供信息。我们注意到,帕金森病(PD)最早的脑损伤部位是呼吸的神经起搏器。因此,我们假设帕金森病患者呼吸的长期时间动态可能会发生改变:我们在 28 名帕金森氏症患者(多数为 H&Y II 期)和 33 名匹配的健康对照者身上应用了一种可穿戴设备,该设备可精确记录鼻腔气流的时间变化。结果:我们观察到鼻气流的时间模式发生了显著变化:我们观察到,与匹配的对照组相比,帕金森病患者鼻腔气流的时间模式发生了明显改变,吸气时间更长,变化更少(平均帕金森病患者 = -1.22 ± 1.9(呼吸特征综合评分),对照组 = 1.04 ± 2.16,Wilcoxon 秩和检验,z = -4.1,效应大小 Cliff's δ = -0.61,95% 置信区间 = -0.79 - (-0.34),P = 4.3 × 10-5)。这种改变的程度使我们仅用 30 分钟的记录就能以 87% 的准确率(AUC = 0.85,79% 的灵敏度(28 例中的 22 例),94% 的特异性(33 例中的 31 例),z = 5.7,P = 3.5 × 10-9)检测出帕金森病,并预测疾病的严重程度(与 UPDRS-Total 评分的相关性:r = 0.49;P = 0.008):我们的结论是,呼吸模式在疾病级联过程中会因 H&Y II 期而改变,我们的方法将来可能会进一步改进,以提供具有诊断和预后价值的指示。
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引用次数: 0
Machine learning for early dynamic prediction of functional outcome after stroke 机器学习用于中风后功能预后的早期动态预测。
IF 5.4 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-11-13 DOI: 10.1038/s43856-024-00666-w
Julian Klug, Guillaume Leclerc, Elisabeth Dirren, Emmanuel Carrera
Prediction of outcome after stroke is critical for treatment planning and resource allocation but is complicated by fluctuations during the first days after onset. We propose a machine learning model that can provide hourly predictions based on the integration of continuous variables acquired within 72 h of hospital admission. We analyzed 2492 admissions for ischemic stroke in the Geneva University Hospital from 01.01.2018 to 31.12.2021, amounting to 2’131’752 unique data points. We developed a transformer model that continuously included clinical, physiological, imaging, and biological data recorded within 72 h of admission. This model was trained to generate hourly predictions of mortality and morbidity. Shapley additive explanations were used to identify the most relevant predictors to explain outcomes for each patient. The MIMIC-III database was used for external validation. Our transformer model predicts mortality, with an area under the receiver operating characteristic curve of 0.830 (95% CI 0.763–0.885) on admission, reaching 0.893 (95% CI 0.839–0.933) 72 h later for a 3-month outcome. Validated in an independent cohort, it outperforms all static models. Based on their mean explanatory weights, the top predictors included continuous clinical evaluation, baseline patient characteristics, timing from admission to acute treatment, and markers of inflammation and organ dysfunction. The performance of our transformer model demonstrates the potential of machine learning models integrating clinical, physiological, imaging, and biological variables over time after stroke. The clinical applicability of our model is further strengthened by access to hourly updated predictions along with accompanying explanations. Stroke is the most frequent cause of disability in industrialized countries. To determine the best treatment and allocate resources, an early and accurate prediction of outcome is essential. Although modern stroke units gather a continuous stream of data, existing tools for outcome prediction are rarely used as they are static and fail to adapt to the evolving condition of the patient. We developed a machine learning model, a computer system learning from existing data, to provide real-time predictions of in-hospital mortality and 3-month outcomes. Our model was able to provide accurate hourly prediction of outcome based on regularly updated clinical data obtained from the patient. This study demonstrates the potential of integrating the continuous data stream recorded in the electronic health record after stroke. Similar predictive models could help personalize treatment planning, empower patients and their families through counseling, and facilitate resource allocation. Klug et al. present a machine learning model for continuous monitoring and prediction of functional outcome after acute ischemic stroke. Integrating clinical, physiological, and biological variables over time, the system detects patients at risk as well as potential cause
背景:中风后的预后预测对治疗计划和资源分配至关重要,但由于发病后最初几天的波动而变得复杂。我们提出了一种机器学习模型,该模型可在整合入院 72 小时内获得的连续变量的基础上提供每小时的预测结果:我们分析了日内瓦大学医院从 2018 年 1 月 1 日至 2021 年 12 月 31 日期间收治的 2492 例缺血性中风患者,共计 2'131'752 个独特的数据点。我们开发了一个转换器模型,该模型持续包含入院 72 小时内记录的临床、生理、影像和生物数据。我们对该模型进行了训练,以生成每小时的死亡率和发病率预测。沙普利加法解释用于识别最相关的预测因素,以解释每位患者的预后。MIMIC-III 数据库用于外部验证:结果:我们的变压器模型可预测死亡率,入院时的接收者操作特征曲线下面积为 0.830(95% CI 0.763-0.885),72 小时后 3 个月结果的接收者操作特征曲线下面积达到 0.893(95% CI 0.839-0.933)。经独立队列验证,该模型优于所有静态模型。根据其平均解释权重,最主要的预测因素包括连续临床评估、患者基线特征、从入院到急性期治疗的时间以及炎症和器官功能障碍标志物:我们的变压器模型的表现证明了机器学习模型整合了中风后一段时间内的临床、生理、影像和生物变量的潜力。通过获取每小时更新的预测结果及相关解释,我们的模型的临床适用性得到了进一步加强。
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引用次数: 0
The effects of remdesivir on long-term symptoms in patients hospitalised for COVID-19: a pre-specified exploratory analysis 雷米替韦对 COVID-19 住院患者长期症状的影响:一项预先指定的探索性分析。
IF 5.4 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-11-12 DOI: 10.1038/s43856-024-00650-4
Thale D. J. Hovdun Patrick-Brown, Andreas Barratt-Due, Marius Trøseid, Anne Ma Dyrhol-Riise, Katerina Nezvalova-Henriksen, Trine Kåsine, Pål Aukrust, Inge C. Olsen, NOR Solidarity consortium
There is an unmet need for treatment of long-term symptoms following COVID-19. Remdesivir is currently the only antiviral approved by the European Medicines Agency for hospitalised patients. Here, we report on the effect of remdesivir in addition to standard of care on long-term symptoms and quality of life in hospitalised patients with COVID-19 as part of the open-label randomised NOR-Solidarity trial (NCT04321616). A total of 185 patients were included in the main trial, of which 118 (60%) were randomised to either remdesivir (n = 42; 36%) or a post-hoc defined control group composed of patients who received standard of care alone or standard of care with hydroxychloroquine (n = 76; 64%). Participants were given quality of life surveys to fill out to gauge their self-reported health over time (the COPD assessment test, the EQ-5D-5L and the RAND SF-36). Here we show that after three months, patients treated with remdesivir do not show significant improvements in stated health compared to those who were not. There are self-reported symptoms of fatigue [mean remdesivir group 2.6 (standard deviation 1.5) v control 2.1 (1.6), 95% confidence interval(CI) −1.17 to 0.15, p = 0.129], shortness of breath [3.0 (1.7) v 2.1 (1.8), 95% CI −1.53 to 0.16, p = 0.110] and coughing [1.8 (1.6) v 1.2 (1.5), 95% CI −1.3 to 0.33, p = 0.237] 3 months after randomisation assessed via the COPD Assessment Test. Our findings indicate that treatment with remdesivir during hospitalisation does not provide any clinically relevant long-term benefit. Remdesivir is a medicine that is used to treat people with COVID-19. It has been found to help people get better faster, but we did not know whether it also relieved them of long-term symptoms such as persistent coughing, fatigue, or shortness of breath. To research this, we randomly assigned hospitalised patients with COVID-19 to either remdesivir on top of their normal care, or only normal care, with or without hydroxychloroquine (a drug later found to have no effect on COVID-19). We then compared participant’s symptoms after 3 months. Our results show that there is probably no benefit of using remdesivir during hospitalisation for long-term symptom relief. Patrick-Brown et al report the findings of a secondary study adjunct to the Nor-Solidarity trial that evaluated remdesivir versus standard of care for the treatment of COVID-19. While remdesivir appears to be safe for use in these patients, there does not appear to be any long-term clinical benefit to its use in terms of long-COVID symptoms.
背景:治疗 COVID-19 后长期症状的需求尚未得到满足。雷米替韦是目前欧洲药品管理局批准用于住院患者的唯一抗病毒药物。在此,我们报告了雷米替韦在标准护理基础上对 COVID-19 住院患者长期症状和生活质量的影响,这是开放标签随机 NOR-Solidarity 试验(NCT04321616)的一部分:主要试验共纳入了185名患者,其中118人(60%)被随机分配到雷米地韦组(n = 42;36%)或由单独接受标准护理或标准护理加羟氯喹的患者组成的事后定义对照组(n = 76;64%)。参试者需填写生活质量调查表,以评估其自我健康状况(慢性阻塞性肺病评估测试、EQ-5D-5L 和 RAND SF-36):结果:我们在此表明,与未接受治疗的患者相比,接受雷米替韦治疗三个月后,患者的健康状况并没有明显改善。自我报告的症状包括疲劳[平均雷米替韦组 2.6(标准差 1.5)v 对照组 2.1(1.6),95% 置信区间(CI)-1.17 至 0.15,p = 0.129]、气短[3.0(1.7) v 2.1 (1.8), 95% CI -1.53 to 0.16, p = 0.110]和咳嗽[1.8 (1.6) v 1.2 (1.5), 95% CI -1.3 to 0.33, p = 0.237]:我们的研究结果表明,住院期间使用雷米替韦治疗不会带来任何临床相关的长期益处。
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引用次数: 0
Author Correction: A cross-sectional and population-based study from primary care on post-COVID-19 conditions in non-hospitalized patients 作者更正:一项关于非住院病人 COVID-19 后病情的初级保健横断面人群研究
IF 5.4 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-11-11 DOI: 10.1038/s43856-024-00661-1
Dominik J. Ose, Elena Gardner, Morgan Millar, Andrew Curtin, Jiqiang Wu, Mingyuan Zhang, Camie Schaefer, Jing Wang, Jennifer Leiser, Kirsten Stoesser, Bernadette Kiraly
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引用次数: 0
An integrated empirical and computational study to decipher help-seeking behaviors and vocal stigma 通过实证和计算综合研究,解读求助行为和声音耻辱感
IF 5.4 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-11-09 DOI: 10.1038/s43856-024-00651-3
Aaron R. Glick, Colin Jones, Lisa Martignetti, Lisa Blanchette, Theresa Tova, Allen Henderson, Marc D. Pell, Nicole Y. K. Li-Jessen
Professional voice users often experience stigma associated with voice disorders and are reluctant to seek medical help. This study deployed empirical and computational tools to (1) quantify the experience of vocal stigma and help-seeking behaviors in performers; and (2) predict their modulations with peer influences in social networks. Experience of vocal stigma and information-motivation-behavioral (IMB) skills were prospectively profiled using online surveys from a total of 403 Canadians (200 singers and actors and 203 controls). Data were used to formulate an agent-based network model of social interactions on vocal stigma (self-stigma and social-stigma) and help-seeking behaviors. Network analysis was performed to evaluate the effect of social network structure on the flow of IMB among virtual agents. Larger social networks are more likely to contribute to an increase in vocal stigma. For small social networks, total stigma is reduced with higher total IMB but not much so for large networks. For agents with high social-stigma and risk for voice disorder, their vocal stigma is resistant to large changes in IMB ( > 2 standard deviations). Agents with extreme IMB and stigma values are likely to polarize their networks faster in larger social groups. We integrated empirical surveys and computational techniques to contextualize vocal stigma and IMB beyond theory and to quantify the interaction among stigma, health-seeking behavior and influence of social interactions. This work establishes an effective, predictable experimental platform to provide scientific evidence in developing interventions to reduce health stigma in voice disorders and other medical conditions. Voice professionals such as singers and actors can experience stigma if they have a voice disorder. This stigma can result from their personal experience and knowledge (internalized) or be based on input from their peers, employment, and healthcare providers (externalized). To understand how negative vocal stigma spreads, we surveyed the stigma experience of voice professionals and developed computational models. We find that people tend to have more polarized stigma experiences when they are in larger social groups. Vocal stigma is not changed by a person’s knowledge, beliefs, and tendency to seek help. Our method could be used to study other stigmatized health conditions. Our research could also be used to reduce stigma and promote more equitable health care for vocal professionals with a voice disorder. Glick et al. investigate the stigma experience and help-seeking behavior in professional singers and actors using de novo data and social simulation. They find that vocal performers experience greater discrimination against their vocal injury with simulation data also predicting that vocal stigma could be worsened with larger social groups.
职业嗓音使用者经常会遭遇与嗓音疾病相关的耻辱,并且不愿寻求医疗帮助。本研究利用实证和计算工具:(1) 量化表演者的嗓音污名化体验和求助行为;(2) 预测社交网络中同伴影响对这些体验和行为的调节作用。这项研究利用在线调查对 403 名加拿大人(200 名歌手和演员以及 203 名对照组)的声带成见经历和信息激励行为(IMB)技能进行了前瞻性分析。数据被用于建立一个基于代理的网络模型,该模型用于分析声带成见(自我成见和社会成见)与求助行为之间的社会互动。通过网络分析,评估了社会网络结构对虚拟代理之间 IMB 流动的影响。较大的社交网络更有可能导致声誉成见的增加。对于小型社交网络而言,总鄙视度会随着总 IMB 的增加而降低,但对于大型网络而言,情况并非如此。对于具有较高社会污名和嗓音障碍风险的代理人来说,他们的嗓音污名对 IMB 的大幅变化(2 个标准差)具有抵抗力。在较大的社会群体中,具有极端 IMB 值和污名值的代理人可能会更快地极化其网络。我们将实证调查和计算技术结合起来,对声誉成见和 IMB 进行了理论之外的背景分析,并量化了成见、健康寻求行为和社会互动影响之间的相互作用。这项工作建立了一个有效、可预测的实验平台,为制定干预措施提供科学依据,以减少嗓音疾病和其他病症的健康成见。歌手和演员等嗓音专业人士如果患有嗓音疾病,可能会遭受成见。这种成见可能来自他们的个人经历和知识(内化),也可能来自他们的同行、就业和医疗服务提供者的意见(外化)。为了了解负面嗓音成见是如何传播的,我们对嗓音专业人员的成见经历进行了调查,并开发了计算模型。我们发现,当人们处于较大的社会群体中时,往往会有更多两极分化的鄙视经历。一个人的知识、信仰和求助倾向并不会改变声带烙印。我们的方法可用于研究其他被污名化的健康状况。我们的研究还可用于减少耻辱感,促进嗓音疾病患者获得更公平的医疗保健。Glick 等人利用新数据和社会模拟研究了专业歌手和演员的成见经历和求助行为。他们发现,声乐表演者在声带损伤方面受到的歧视更大,模拟数据还预测,声带成见可能会随着社会群体的扩大而加剧。
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引用次数: 0
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Communications medicine
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