surrogate markers

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  • 文章类型: Journal Article
    全球重大健康问题,慢性乙型肝炎需要精确的预后和诊断指标来指导临床。本文重点介绍了慢性乙型肝炎的检测和预后中使用的主要标志物的临床重要性和当前问题。持续和持续感染的重要指标是乙型肝炎表面抗原。乙型肝炎病毒DNA定量监测有助于评估病毒载量和肝癌风险。虽然肝脏损害的有限证据是由丙氨酸转氨酶水平提供,乙型肝炎核心抗体证实急性感染。血清转化为乙型肝炎e抗体与较低的疾病发展风险有关,乙型肝炎e抗原状态是一个关键的预后因素。治疗选择由肝脏活检或微创肝纤维化检测指导。乙型肝炎病毒的基因型和宿主变量通过增加疾病的变异性来影响预后。血清纤维化标志物提供了评估疾病严重程度的非侵入性技术,如基于4项标准的纤维化评分和天冬氨酸转氨酶/血小板比值指数.在评估肝损伤时区分不同病毒阶段和增加特异性的指标要求是慢性乙型肝炎研究面临的挑战之一。尽管很难找到可靠的抵抗生物标志物,特别是在肝细胞癌风险估计方面,有先进的方法,其中包括成像和组学,可以帮助提高诊断和预后的准确性。早期干预措施可以使用诊断和预后来改善患者的预后,因为它们在管理慢性乙型肝炎的复杂景观方面非常有效。特别是那些将支持成功的治疗计划与慢性乙型肝炎病毒(HBV)的人的发展,是科学研究,技术进步和合作。
    A major worldwide health concern, chronic hepatitis B necessitates precise prognostic and diagnostic indicators for clinical guidance. This article highlights the clinical importance and current issues of the major markers used in both the detection and prognosis of chronic hepatitis B. An important indicator of an ongoing and persistent infection is the hepatitis B surface antigen. Hepatitis B virus DNA quantification monitoring aids in assessing viral load and hepatic cancer risk. While limited evidence of liver damage is provided by alanine aminotransferase levels, the hepatitis B core antibody verifies acute infection. Seroconversion to the hepatitis B e antibody is linked to a lower risk of disease development, and the hepatitis B e antigen status is a critical prognostic factor. Treatment choices are guided by a biopsy of the liver or minimally invasive liver fibrosis detection. Genotypes of the hepatitis B virus and host variables influence the prognosis by adding to the disease\'s variability. Noninvasive techniques to evaluate the severity of the disease are provided by serum markers of fibrosis, such as the fibrosis score based on four criteria and the aspartate aminotransferase-to-platelet ratio index. The requirement for indicators that distinguish between distinct viral phases and increase specificity in evaluating liver damage is one of the challenges facing chronic hepatitis B research. Even though it is quite difficult to find reliable biomarkers for resistance especially when it comes to hepatocellular cancer risk estimation, there are advanced methods, which include imaging and omics that can help in improving the accuracy of the diagnostics and prognosis. Interventions early point that improve patient outcomes are made possible using diagnostics and prognostics as they are quite effective in managing the complicated landscape of chronic hepatitis B. Key in addressing these challenges today and improving the diagnostic and prognostic markers in the future, particularly those that would support the development of successful treatment plans for people living with chronic hepatitis B virus (HBV), are scientific research, technological advances and collaborations.
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  • 文章类型: Journal Article
    肝脏脂肪变性伴炎症,膨胀的肝细胞,和潜在的纤维化定义非酒精性脂肪性肝炎(NASH),可能会导致肝硬化.虽然肝活检仍是诊断NASH的金标准,已经研究了许多非侵入性替代标记以减少对这种侵入性技术的需求。在这篇综述中,我们提出了几种目前评估的生物标志物,分数,和评估NASH的指标。
    在主要医学文献数据库中进行搜索。我们搜索了评估非侵入性标志物的观察性研究,分数,和面板预测NASH。
    几种促炎标志物,炎症和凋亡生物标志物,以及复杂模型在预测NASH方面的研究。促炎标志物包括C反应蛋白,铁蛋白,肿瘤坏死因子-α,白细胞介素-6,五聚素-3和中性粒细胞胞外陷阱。炎症和凋亡生物标志物包括细胞分裂素-18,脂肪细胞因子,脂质氧化面板,纤溶酶原激活剂抑制剂-1,以及自由基介导的亚油酸氧化产物。此外,几个研究的复杂模型,如纳什测试,NashTest-2,将CK18片段与其他生物标志物如ALT和MetS的存在配对,头发模型,acNASH,NAFIC得分,还研究了内脏脂肪指数。
    各种诊断小组显示出诊断NASH的良好预测值。然而,非侵入性替代标记目前无法取代肝活检。然而,其临床意义主要在于对患者进行肝活检,减少与程序相关的财务负担。
    UNASSIGNED: Hepatic steatosis with inflammation, inflated hepatocytes, and potential fibrosis defines non-alcoholic steatohepatitis (NASH), which can possibly lead to liver cirrhosis. Although liver biopsy is still the gold standard for diagnosing NASH, numerous non-invasive surrogate markers have been investigated to reduce the need for this invasive technique. In this review we present several currently assessed biomarkers, scores, and indexes in assessing NASH.
    UNASSIGNED: A search in the main medical literature databases was conducted. We searched for observational studies evaluating non-invasive markers, scores, and panels in predicting NASH.
    UNASSIGNED: Several proinflammatory markers, inflammation and apoptosis biomarkers, as well as complex models have been studied in predicting NASH. Proinflammatory markers include C-reactive protein, ferritin, tumor necrosis factor-α, interleukin-6, pentraxin-3, and neutrophil extracellular traps. Inflammation and apoptosis biomarkers include cytokineratin-18, adipocytokines, lipid oxidation panels, plasminogen activator inhibitor-1, and products of free radical-mediated oxidation of linoleic acid. Moreover, several studied complex models such as NashTest, NashTest-2, pairing CK18 fragments with other biomarkers such as ALT and the presence of MetS, the HAIR model, acNASH, NAFIC score, Visceral Adiposity Index have also been studied.
    UNASSIGNED: A variety of diagnostic panels have shown good predictive values for diagnosing NASH. Nevertheless, non-invasive surrogate markers are currently unable to replace liver biopsy. However, their clinical significance is mainly in triaging patients for liver biopsy, reducing the financial burden associated with the procedure.
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  • 文章类型: Journal Article
    一些研究表明,HTLV-1感染可能与不符合HAM诊断标准的更广泛的神经系统和临床表现有关。这些情况可能会在以后发展为HAM或构成中间临床形式:中间综合征(IS),无症状的HTLV-1携带者和患有完全脊髓病的中间点。因此,我们确定了HAM病例在HTLV-1无症状和IS患者中的发生率,和临床/实验室相关标志物。本研究共纳入204例HTLV-1阳性患者,分为两组:第1组,包括145名无症状的HTLV-1受试者(ASY),和第2组,包括59例患者在三个以上的系统中具有炎性临床症状和高的前病毒负荷(PVL)。在60个月的随访期间,年龄从47岁到79岁,59例最初诊断为IS发展为HAM(iHAM)的患者中有10例,最初的145例ASY的两名患者直接发展了HAM。妇女在所有群体中更为普遍。对于iHAM患者来说,年龄从20岁到72岁,平均值为53(±15标准差)。年龄较大与HAM的发展有关,较高的PVL和IS;然而,没有任何具体的症状或临床体征,这与iHAM的风险有关。总之,IS病例可能是HAM发展的早期阶段。这些发现表明,我们队列中的发病率比以前报道的要高。
    Several studies suggest that HTLV-1 infection may be associated with a wider spectrum of neurological and clinical manifestations that do not meet diagnostic criteria for HAM. These conditions may later progress to HAM or constitute an intermediate clinical form: intermediate syndrome (IS), a mid-point between asymptomatic HTLV-1 carriers and those with full myelopathy. Thus, we determined the incidence of HAM cases in the HTLV-1-asymptomatic and IS patients, and the clinical/laboratory associated markers. A total of 204 HTLV-1-positive patients were included in this study, divided into two groups: Group 1, including 145 asymptomatic HTLV-1 subjects (ASY), and Group 2, including 59 patients with inflammatory clinical symptoms in more than three systems and a high proviral load (PVL). During a 60-month follow-up time, with the age ranging from 47 to 79 years, ten patients of the fifty-nine initially diagnosed as IS developed HAM (iHAM), and two patients of the initial 145 ASY developed HAM directly. Women were more prevalent in all groups. For the iHAM patients, the age ranged from 20 to 72 years, with a mean of 53 (±15 SD). Older age was associated with the development of HAM, higher PVL and IS; however, there was no any specific symptom or clinical sign, that was associated with risk for iHAM. In conclusion, IS cases could be an early phase of development of HAM. These findings show the presence of higher incidence probabilities in our cohort than previously reported.
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  • 文章类型: Journal Article
    炎症性肠病(IBD)包括两种类型的慢性肠道疾病:克罗恩病和溃疡性结肠炎。在长期的溃疡性结肠炎疾病活动中,组织学持续性炎症与复发风险增加有关,长期使用皮质类固醇,即使达到内镜缓解。在克罗恩病,病变的不连续性质和透壁性炎症限制了标准化的组织学评估.目前的研究证据表明,除了临床和内窥镜治疗外,在IBD患者中,实现组织学愈合是评估疾病活动性和缓解情况的终点,该终点涉及更好的长期疾病结局.即使在没有内窥镜病变的情况下,组织学改变也可能持续存在。由于这些原因,新的先进技术有望通过改善内窥镜和组织学评估来彻底改变IBD领域,疾病表征,以及最终的病人护理,在日常实践中具有客观评估病变的既定作用。这篇综述概述了在IBD中纳入微观评估的重要性,使用经过验证的诊断方法和日常临床实践的评分系统,强调深度疾病缓解状态的临床益处。
    Inflammatory bowel disease (IBD) comprises two types of chronic intestinal disorders: Crohn\'s disease and ulcerative colitis. In long-standing ulcerative colitis disease activity, histological persistent inflammation has been linked to an increased risk of relapse, and long-term corticosteroid use, even when endoscopic remission is reached. In Crohn\'s disease, the discontinuous nature of lesions and transmural inflammation have limited the standardized histological assessment. The current evidence from research proposes that besides clinical and endoscopic healing, the achievement of histological healing constitutes an endpoint to assess disease activity and remission in IBD patients concerning better long-term disease outcomes. Histological alterations may persist even in the absence of endoscopic lesions. For these reasons, new advanced techniques promise to revolutionize the field of IBD by improving the endoscopic and histologic assessment, disease characterization, and ultimately patient care, with an established role in daily practice for objective assessment of lesions. This review outlines the importance of including microscopic evaluation in IBD, highlighting the clinical benefits of a deep state of disease remission using validated diagnostic methods and scoring systems for daily clinical practice.
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  • 文章类型: Journal Article
    临床试验通常收集中间或替代终点,而不是真正的目标终点。重要的是,对替代终点的治疗效果准确地预测对真实终点的治疗效果。在某些设置中,建议的替代端点与真实端点呈正相关,但是治疗对替代终点和真实终点有相反的影响,一种标有“替代悖论”的现象。协变量信息可能有助于预测个体的替代悖论风险。在这项工作中,我们提出了使用meta分析因果关联框架将协变量纳入评估替代悖论风险的方法.这些措施计算治疗对替代终点和真实终点产生相反影响的概率,并确定对替代终点的积极治疗效果的大小,这将降低对真实终点产生负面治疗影响的风险,作为协变量的函数,允许协变量对替代终点和真实终点的影响因试验而异。
    Clinical trials often collect intermediate or surrogate endpoints other than their true endpoint of interest. It is important that the treatment effect on the surrogate endpoint accurately predicts the treatment effect on the true endpoint. There are settings in which the proposed surrogate endpoint is positively correlated with the true endpoint, but the treatment has opposite effects on the surrogate and true endpoints, a phenomenon labeled \"surrogate paradox\". Covariate information may be useful in predicting an individual\'s risk of surrogate paradox. In this work, we propose methods for incorporating covariates into measures of assessing the risk of surrogate paradox using the meta-analytic causal association framework. The measures calculate the probability that a treatment will have opposite effects on the surrogate and true endpoints and determine the size of a positive treatment effect on the surrogate endpoint that would reduce the risk of a negative treatment effect on the true endpoint as a function of covariates, allowing the effects of covariates on the surrogate and true endpoint to vary across trials.
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  • 文章类型: Editorial
    暂无摘要。
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  • 文章类型: Journal Article
    针对丁型肝炎的流行病学研究和最近的荟萃分析报告了该疾病的患病率差异很大。在所有乙型肝炎表面抗原(HBsAg)阳性患者的4.5%至15%之间被认为藏有丁型肝炎病毒。患病率的突然变化可归因于几个因素。毫不奇怪,已发表的文献表明,在合并病毒性肝炎流行的地区以及具有促进水平转移的高风险做法的人群中,该疾病的患病率更高。同时,该疾病的自然史受病毒基因型的影响,丁型肝炎病毒(HDV)RNA水平,HBV-HDV共优势,HBsAg滴度,HBV基因型,营养状况,艾滋病毒共同感染,和事先治疗。这些因素共同导致纤维化的加速发展和肝细胞癌的风险增加。基因型1的过度感染导致快速进展为肝硬化,缓解率较低。基因型3遵循积极的过程,但显示出对干扰素治疗的良好反应。其他基因型有更好的结果。导致这些结果的疾病过程可以通过HDV特异性模型来跟踪,该模型整合了临床替代标记和流行病学因素,如年龄,区域,丙氨酸氨基转移酶(ALT),γ-谷氨酰转移酶,白蛋白,血小板和胆碱酯酶,和肝脏僵硬。
    Epidemiological studies and recent metanalyses addressing hepatitis D have reported a wide variation in the prevalence of the disease. Between 4.5% to 15% of all hepatitis B surface antigen (HBsAg) positive patients are thought to harbor the hepatitis D virus. The emergent variation in prevalence can be attributed to several factors. Unsurprisingly, published literature shows that the prevalence of the disease is higher in areas where aggregate viral hepatitis infections are endemic and amongst groups with high-risk practices facilitating the horizontal transfer. Meanwhile, the natural history of the disease is influenced by the genotype of the virus, the hepatitis D virus (HDV) RNA levels, HBV-HDV codominance, HBsAg titers, HBV genotype, nutritional status, HIV co-infection, and prior treatment. Together these factors contribute to the accelerated development of fibrosis and the increased risk of hepatocellular carcinoma. Superinfection with genotype 1 results in rapid progression to cirrhosis with lower rates of remission. Genotype 3 follows an aggressive course but shows a good response to interferon therapy. Other genotypes have better outcomes. The course of the disease leading to these outcomes can be tracked by HDV-specific models integrating clinical surrogate markers and epidemiological factors such as age, region, alanine aminotransferase (ALT), gamma-glutamyl transferase, albumin, platelets and cholinesterase, and liver stiffness.
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  • 文章类型: Journal Article
    背景:尽管尿动力学评估是诊断和治疗后尿道瓣膜(PUV)膀胱功能障碍的基石,然而,了解是否有任何非侵入性的替代成像标记可能会有所帮助。
    目的:研究PUV患者尿动力学证实膀胱功能障碍的各种影像替代标记物的诊断准确性。
    方法:这项为期两年的横断面研究包括38名经内窥镜检查证实为PUV的儿童。根据膀胱功能对尿动力学的影响,将患者分为2组:第1组:膀胱功能正常的PUV(n:17,44.7%);第2组:膀胱功能受损的PUV(n:21,55.3%)。排尿功能障碍,复发性尿路感染(UTI)的发生率,多尿,肾积水等级,比较两组膀胱后输尿管直径(mm)和逼尿肌壁厚度(DWTmm)。研究了初次就诊和最终治疗后的MCU,并为每位患者分配了膀胱敌意评分(BHS),并在两组中进行了比较。使用SpearmanRank相关性进行膀胱功能受损与临床和放射学变量之间的相关性,并绘制数据接受者工作曲线(ROC)以确定预测PUV中膀胱功能障碍概率的临界值。
    结果:评估时的平均年龄为6.1±4.2岁,平均随访时间为5±3.9年(中位数:3.5年)。排尿功能障碍,持续或恶化的III级和IV级肾盂积水,膀胱后输尿管直径≥13.1mm(诊断准确率:68.4%,AUC:0.738),全膀胱DWT≥1.85mm(诊断准确率:81.6%,AUC:0.846)和预处理BHS≥5.5(诊断准确率:71.4%,AUC:0.763)是膀胱功能受损的临床和影像学预测因子。两组比较分析如表所示。
    结论:临床和影像学参数无法令人信服地确定膀胱功能障碍的类型,这通常是适当管理PUV患者所需的。逼尿肌壁厚增加提示潜在的膀胱功能障碍,而容量小的高渗性膀胱的逼尿肌平均壁厚高于肌源性衰竭的患者,差异无统计学意义(p:0.41)。在近三分之一的患者中,尝试通过MCU成像来预测潜在的膀胱功能障碍可能是错误的。因此,这些成像参数与尿动力学是互补和连续的,这当然仍然是评估PUV膀胱功能障碍的金标准研究。
    Although urodynamic evaluation forms the cornerstone of diagnosis and management of bladder dysfunction in posterior urethral valves (PUV), yet it could be helpful to learn if there are any non-invasive surrogate imaging markers for the same.
    To study the diagnostic accuracy of various imaging surrogate markers of urodynamic proven bladder dysfunction in PUV.
    This cross-sectional study over two years included 38 children of endoscopically proven PUV. Based on bladder function on Urodynamics the patients were divided into 2 groups: Group 1: PUV with normal bladder function (n: 17, 44.7%); Group 2: PUV with impaired bladder function (n: 21, 55.3%). Voiding dysfunction, incidence of recurrent urinary tract infection (UTI), polyuria, grade of hydronephrosis, retrovesical ureteric diameter (mm) and detrusor wall thickness (DWT mm) was compared in the two groups. MCU at initial presentation and post definitive treatment was studied and a bladder hostility score (BHS) was assigned to each patient and compared in the two groups. Correlation between impaired bladder function and clinical and radiological variables was performed by using Spearman Rank correlation and data receiver operating curves (ROC) were plotted to identify the critical values predicting the probability of bladder dysfunction in PUV.
    Mean age at evaluation was 6.1 ± 4.2 years with a mean follow-up of 5 ± 3.9 years (median: 3.5 years). Voiding dysfunction, persistent or worsening grade III and IV hydroureteronephrosis, retrovesical ureter diameter ≥13.1 mm (diagnostic accuracy: 68.4%, AUC: 0.738), DWT on full bladder ≥1.85 mm (diagnostic accuracy: 81.6%, AUC: 0.846) and pretreatment BHS ≥5.5 (diagnostic accuracy: 71.4%, AUC: 0.763) were the clinical and imaging predictors of impaired bladder function. Comparative analysis of the two groups is as shown in table.
    Clinical and imaging parameters are unable to convincingly identify the type of bladder dysfunction which is often required to manage PUV patients appropriately. Increased detrusor wall thickness suggests underlying bladder dysfunction and while those with small capacity hypertonic bladders have higher mean detrusor wall thickness than those with myogenic failure, the difference was not statistically significant (p: 0.41). Attempts to predict underlying bladder dysfunction by MCU imaging may be erroneous in nearly one-third of the patients. Thus, these imaging parameters are complementary and sequential to urodynamic, which certainly continues to be the gold standard investigation to assess bladder dysfunction in PUV.
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  • 文章类型: Journal Article
    皮肤自发荧光(SAF)是晚期糖基化终产物(AGEs)积累的标志,并与糖尿病大血管病变有关。然而,SAF在检测大血管病变方面是否优于动脉粥样硬化的常规标志物,如颈动脉内中膜厚度(IMT)和脉搏波传导速度(PWV),目前尚不清楚.
    我们招募了845名患有SAF的2型糖尿病患者,IMT,和在基线测量的PWV。研究了基线时大血管病变的发生率和2年随访期间的新心血管事件。使用AGE读数器测量SAF。通过计算机断层扫描对485例患者进行了冠状动脉钙化(CAC)测量。外周动脉疾病(PAD)定义为踝肱血压比值≤0.9。
    SAF,IMT,和PWV之间存在显着相关,和年龄,糖尿病持续时间,和估计的肾小球滤过率是它们的强混杂因素。调整混杂因素后,SAF与基线卒中和新卒中相关,但不是冠状动脉疾病(CAD)或PAD。SAF与CAD之间的关系与SAF与CAC之间的关系一致。多变量分析显示,独立于IMT和PWV,SAF与基线和新卒中显著相关。最大IMT与基线CAD显著相关,PAD,和中风,但不是新的中风,而PWV与新卒中相关。
    在糖尿病性大血管病变中,SAF是一种很好的卒中生物标志物,但不适用于CAD和PAD。
    在线版本包含补充材料,可在10.1007/s13340-022-00608-8获得。
    UNASSIGNED: Skin autofluorescence (SAF) is a marker for the accumulation of advanced glycation end products (AGEs), and is associated with diabetic macroangiopathy. However, whether SAF is superior to conventional markers of atherosclerosis such as carotid intima-media thickness (IMT) and pulse wave velocity (PWV) in detecting macroangiopathy remains unclear.
    UNASSIGNED: We recruited 845 patients with type 2 diabetes enrolled in a community diabetes cohort (ViNA cohort) who had SAF, IMT, and PWV measured at baseline. The prevalence of macroangiopathy at baseline and new cardiovascular events during the 2-year follow-up period was investigated. SAF was measured using an AGE reader. Coronary artery calcification (CAC) was measured by computed tomography in 485 patients. Peripheral artery disease (PAD) was defined as the ankle-brachial blood pressure ratio of ≤ 0.9.
    UNASSIGNED: SAF, IMT, and PWV were significantly correlated with each other, and age, diabetes duration, and estimated glomerular filtration rate were their strong confounders. SAF was associated with baseline stroke and new stroke after adjusting for confounders, but not with coronary artery disease (CAD) or PAD. The nonsignificant relationship between SAF and CAD was consistent with the relationship between SAF and CAC. Multivariate analysis showed a significant association of SAF with baseline and new stroke independent of IMT and PWV. Maximum-IMT was significantly associated with baseline CAD, PAD, and stroke, but not with a new stroke, whereas PWV was associated with a new stroke.
    UNASSIGNED: Among diabetic macroangiopathies, SAF is a good stroke biomarker, but not for CAD and PAD.
    UNASSIGNED: The online version contains supplementary material available at 10.1007/s13340-022-00608-8.
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  • 文章类型: Journal Article
    在临床背景下,沟通能力不足的患者的疼痛评估通常由训练有素的医务人员在外部进行。自动疼痛识别(APR)可以在这方面做出重大贡献。特此,主要使用视频摄像头和生物信号传感器捕获疼痛反应。Primary,在重症监护医学中,在镇痛镇静开始期间自动监测疼痛具有最高的相关性。在这种情况下,在数据安全性方面,面部肌电图(EMG)代表了通过视频记录面部表情的替代方法。在本研究中,分析特定的生理信号以确定,是否可以区分术后镇痛前后给药。明确,测试了面部肌电图对镇痛效果的影响。
    N=38名计划进行手术干预的患者。手术后,患者被转移到中间护理。记录生物信号,并仔细记录所有剂量的镇痛剂,直到将其转移回普通病房。
    几乎每个生物信号特征都能够在止痛药之前和之后之间进行明显区分。我们发现面部肌电图的效果最大(r=0.56)。
    本研究的结果,基于BioVid和X-ITE疼痛数据集的研究结果,工作人员和患者的接受表明,现在开发APR原型是合适的.
    UNASSIGNED: In the clinical context, the assessment of pain in patients with inadequate communication skills is standardly performed externally by trained medical staff. Automated pain recognition (APR) could make a significant contribution here. Hereby, pain responses are captured using mainly video cams and biosignal sensors. Primary, the automated monitoring of pain during the onset of analgesic sedation has the highest relevance in intensive care medicine. In this context, facial electromyography (EMG) represents an alternative to recording facial expressions via video in terms of data security. In the present study, specific physiological signals were analyzed to determine, whether a distinction can be made between pre-and post-analgesic administration in a postoperative setting. Explicitly, the significance of the facial EMG regarding the operationalization of the effect of analgesia was tested.
    UNASSIGNED: N = 38 patients scheduled for surgical intervention where prospectively recruited. After the procedure the patients were transferred to intermediate care. Biosignals were recorded and all doses of analgesic sedations were carefully documented until they were transferred back to the general ward.
    UNASSIGNED: Almost every biosignal feature is able to distinguish significantly between \'before\' and \'after\' pain medication. We found the highest effect sizes (r = 0.56) for the facial EMG.
    UNASSIGNED: The results of the present study, findings from research based on the BioVid and X-ITE pain datasets, staff and patient acceptance indicate that it would now be appropriate to develop an APR prototype.
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