Tm

TM
  • 文章类型: Journal Article
    现代远程医疗(TM)技术在增强医疗保健服务中辅助技术的获取方面发挥着至关重要的作用。然而,除非在服务用户(患者)中被广泛接受,否则这项技术的全部好处将无法实现。这项研究旨在调查患者信任和感知风险对医疗保健辅助技术接受TM的影响。
    通过专家反馈和试点研究,开发和完善了一种综合测量仪器,导致917名参与者的数据收集。指导本研究的理论框架是基于TM中的信任因素,这有助于概念化影响患者接受TM的因素。
    该研究揭示了患者对TM的信任存在显着差距,并强调了感知风险的多面性,强调需要单独考虑个别风险因素。结果还表明,对TM的技术可靠性和感知有效性的信任是影响其采用的关键因素。研究结果强调了在服务用户之间建立信任并提高TM可靠性以实现理想的医疗结果的重要性。
    总而言之,为了促进TM对辅助技术的广泛接受,涉及医疗保健提供者的多方面方法,组织,政府对于解决患者的问题至关重要,增强信任,并推广这项技术的好处。
    UNASSIGNED: Modern telemedicine (TM) technologies play a crucial role in enhancing access to Assistive Technology in healthcare services. However, the full benefits of this technology will not be realized unless it is widely accepted among service users (patients). This study aimed to investigate the impact of patient trust and perceived risk on the acceptance of TM for Assistive Technology in healthcare.
    UNASSIGNED: A comprehensive survey instrument was developed and refined through expert feedback and a pilot study, leading to data collection from 917 participants. The theoretical framework guiding this research was based on the Trust factors in TM, which helped in conceptualizing the factors influencing patient acceptance of TM.
    UNASSIGNED: The study revealed a significant gap in patient trust in TM and highlighted the multifaceted nature of perceived risk, emphasizing the need to consider individual risk factors separately. Results also indicated that trust in technological reliability and the perceived effectiveness of TM were critical factors influencing its adoption. The findings underscore the importance of building trust among service users and promoting the reliability of TM for achieving desirable medical outcomes.
    UNASSIGNED: In conclusion, to facilitate widespread acceptance of TM for Assistive Technology, a multi-faceted approach involving healthcare providers, organizations, and governments is essential to address patient concerns, enhance trust, and promote the benefits of this technology.
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  • 文章类型: Journal Article
    背景:终末期肾病(ESRD)是慢性肾病(CKD)的最后阶段。
    目的:我们旨在分析血清血栓调节蛋白(TM)的表达差异,血小板活化因子(PAF),和P-选择素(CD62P)在自体动静脉瘘(AVF)患者中的表达及与血管通路功能的相关性。
    方法:对病例资料进行回顾性分析。此外,选择160例AVF维持性血液透析患者作为AVF组,选择150例健康受试者作为健康对照组。根据血管通路的功能,将AVF组患者分为A组(n=50,在首次建立AVF后),B组(n=64,血液透析治疗后血管通路功能正常),和C组(n=46,血管通路衰竭)。进行Pearson分析以探讨血清TM,PAF,CD62P含量,和血管病理检查指标,为了评估TM的价值,PAF,和CD62P水平在预测AVF患者血管通路衰竭中的作用。
    结论:血清TM水平,PAF,CD62P分别与CD68和MCP-1的表达呈正相关(p<.001)。血清TM与PAF、CD62P水平呈正相关(p<.001),PAF与CD62P水平呈正相关(p<.001),分别。血清TM水平,PAF和CD62P是AVF患者血管通路衰竭的危险因素(p<0.05)。血清TM曲线下面积,预测AVF患者血管通路衰竭的PAF和CD62P水平为0.879。
    结论:血清TM水平,PAF,AVF患者的CD62P与AVF患者的血管通路功能相关,这对于维持血管通路功能的稳定性非常重要,对预测AVF患者血管通路衰竭/障碍有一定的价值,可以推广应用。
    BACKGROUND: End-stage renal disease (ESRD) is the final stage of chronic kidney disease (CKD).
    OBJECTIVE: We aimed to analyze the expression differences of serum thrombomodulin (TM), platelet-activating factor (PAF), and P-selectin (CD62P) in patients with autologous arteriovenous fistula (AVF) and the correlation with vascular access function.
    METHODS: The case data were retrospectively analyzed. Moreover, 160 patients with AVF maintenance hemodialysis were selected as the AVF group, and 150 healthy participants were selected as the healthy control group. According to the function of vascular access, patients in the AVF group were divided into Group A (n = 50, after the first establishment of AVF), Group B (n = 64, normal vascular access function after hemodialysis treatment), and Group C (n = 46, vascular access failure). Pearson analysis was conducted to explore the correlation between serum TM, PAF, CD62P content, and vascular pathological examination indicators, to evaluate the value of TM, PAF, and CD62P levels in predicting vascular access failure in patients with AVF.
    CONCLUSIONS: The serum levels of TM, PAF, and CD62P were positively correlated with the expressions of CD68 and MCP-1, respectively (p < .001). Serum TM was positively correlated with the levels of PAF and CD62P (p < .001), and PAF was positively correlated with the levels of CD62P (p < .001), respectively. Serum levels of TM, PAF and CD62P were risk factors for vascular access failure in AVF patients (p < .05). The area under the curve of serum TM, PAF and CD62P levels in predicting vascular access failure in AVF patients was 0.879.
    CONCLUSIONS: The serum levels of TM, PAF, and CD62P in AVF patients were correlated with the vascular access function of AVF patients, which was very important for maintaining the stability of vascular access function, and had certain value in predicting vascular access failure/disorder in AVF patients, and could be popularized and applied.
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  • 文章类型: Journal Article
    一些作者已经报道了怀孕期间止血的生理变化。本研究旨在建立止血生物标志物凝血酶-抗凝血酶复合物(TAT)的参考区间,α2-纤溶酶抑制剂-纤溶酶复合物(PIC),血栓调节蛋白(TM)和组织纤溶酶原激活物-抑制剂复合物(tPAI-C),在健康的怀孕中。排除异常值后,共有496名健康孕妇(128名早孕期,142中期妊娠,从深圳宝安妇女儿童医院招募了107名孕晚期和119名临产前)和103名健康非孕妇。止血生物标志物,TAT,PIC,TM和tPAI-C,通过使用在HISCL自动分析仪上进行的定量化学发光酶免疫分析法进行测量。计算中位数和参考间隔(第2.5百分位数和第97.5百分位数)以建立健康孕妇的三个月特异性参考间隔。TAT的参考间隔,PIC,前三个月的TM和tPAI-C为0.7-7.61µg/L,0.2-0.9mg/L,2.8-11.0TU/ml,和1.2-6.51µg/L,分别。妊娠中期的参考间隔为1.7-12.01µg/L,0.2-1.0mg/L,3.7-11.6TU/ml,和2.8-8.81µg/L,分别。妊娠晚期的参考间隔为2.7-16.11µg/L,0.1-1.4mg/L,2.9-12.9TU/ml,和1.9-8.01µg/L,分别。在临产前,参考间隔为4.8-32.91µg/L,0.2-1.9mg/L,4.2-12.6TU/ml,和2.8-15.41µg/L,分别。TAT的妊娠参考间隔,PIC,提供健康妊娠的TM和tPAI-C,但仅限于整个怀孕期间浓度不断增加的TAT,非孕妇的参考区间不适用.
    Physiological changes in hemostasis during pregnancy have been reported by several authors. This study aimed at establishing reference intervals for the hemostasis biomarkers thrombin-antithrombin complex (TAT), α2-plasmininhibitor-plasmin complex (PIC), thrombomodulin (TM) and tissue plasminogen activator-inhibitor complex (tPAI-C), in healthy pregnancies. After excluding outliers, a total of 496 healthy pregnant women (128 first-trimester, 142 second-trimester, 107 third-trimester and 119 pre-labor) and 103 healthy nonpregnant women were enrolled from Shenzhen Bao\'an Women\'s and Children\'s Hospital. Hemostasis biomarkers, TAT, PIC, TM and tPAI-C, were measured by using a quantitative chemiluminescence enzyme immunoassay performed on HISCL automated analysers. The median and reference intervals (the 2.5th and 97.5th percentiles) were calculated to establish trimester-specific reference intervals for healthy pregnant women. The reference intervals for TAT, PIC, TM and tPAI-C in the first trimester were 0.7-7.6 1 µg/L, 0.2-0.9 mg/L, 2.8-11.0 TU/ml, and 1.2-6.5 1 µg/L, respectively. The reference intervals in the second trimester were 1.7-12.0 1 µg/L, 0.2-1.0 mg/L, 3.7-11.6 TU/ml, and 2.8-8.8 1 µg/L, respectively. The reference intervals in the third trimester were 2.7-16.1 1 µg/L, 0.1-1.4 mg/L, 2.9-12.9 TU/ml, and 1.9-8.0 1 µg/L, respectively. At pre-labor, the reference intervals were 4.8-32.9 1 µg/L, 0.2-1.9 mg/L, 4.2-12.6 TU/ml, and 2.8-15.4 1 µg/L, respectively. Gestational reference intervals for TAT, PIC, TM and tPAI-C in healthy pregnancies are provided, but only for TAT with increasing concentrations throughout pregnancy, the reference intervals for non-pregnant were not applicable.
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  • 文章类型: Journal Article
    聚乙烯吡咯烷酮(PVP)可用于以有利的方式生产上转换纳米颗粒(UCNP)。即,在适度的温度下,在开放的空气条件下,使用简单的热板和烧瓶设备。然而,PVP参数对UCNPs形成的影响以前没有研究过。在这项探索性研究中,我们确定PVP的分子量和PVP的相对量可以极大地影响NaYF4:Yb的形态和直径,通过PVP辅助途径产生的ErUCNP。在标称量的PVP下,将合成中PVP的分子量在10,000g/mol(PVP10)之间变化,40,000g/mol(PVP40),和55,000g/mol(PVP55),对UCNP形态影响最小,而将反应中PVP10和PVP40的量减少到标称量的10%会产生两个显着影响:(1)产生更大范围的UCNP直径,以及(2)产生意想不到的菱形子群。形状的UCNPs。本体和单个纳米颗粒分析表明,所有UCNP形貌均为立方(α相)晶体结构,由NaYF4:Yb组成,呃。当PVP参数变化时,光发射特性仅表现出适度的绿色和红色发光发射比。然而,单独生产的PVP40NaYF4:Yb,TmUCNP表现出更强烈的双波段蓝色/红色发射。这项探索性工作表明,在UCNP的合成中调整PVP含量可以极大地改变所产生的UCNP的形态,应在实验设计中仔细考虑。然而,PVP在该合成中的作用机制尚不清楚.最终,仍然需要进一步的工作来充分阐明相关的化学以实现PVP-UCNP合成的完全控制。
    Polyvinylpyrrolidone (PVP) can be used to produce upconversion nanoparticles (UCNPs) in an advantageous manner, i.e. at modest temperatures in open-to-air conditions with simple hotplate and flask apparatus. However, the influence of PVP parameters on the formation of UCNPs has not been previously investigated. In this exploratory study, we establish that PVP molecular weight and relative amount of PVP can greatly influence the morphology and diameter of NaYF4:Yb,Er UCNPs produced via the PVP-assisted route. At nominal amounts of PVP, varying the molecular weight of PVP in synthesis between 10,000 g mol-1(PVP10), 40,000 g mol-1(PVP40), and 55,000 g mol-1(PVP55), had minimal effect on UCNP morphology, whereas reducing the quantity of PVP10 and PVP40 in the reaction to 10% of the nominal amount resulted in two notable effects: (1) the generation of a greater range of UCNP diameters and (2) the production of an unexpected sub-population of rhombus-shaped UCNPs. Bulk and individual nanoparticle analysis indicates that all UCNP morphologies were cubic (α-phase) crystal structure and consisted of NaYF4:Yb,Er. Optical emission properties exhibited only modest green and red luminescence emission ratio when PVP parameters were varied. However, separately produced PVP40 NaYF4:Yb,Tm UCNPs exhibited a much more intense and dual-band blue/red emission. This exploratory work demonstrates that tailoring PVP content in synthesis of UCNPs can greatly alter morphology of UCNPs produced and should be carefully considered in experimental design. However, the underlying mechanisms of action of the role PVP plays in this synthesis remain unclear. Ultimately, significant further work is still required to fully elucidate the relevant chemistry to achieve full control of PVP-UCNP synthesis.
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  • 文章类型: Journal Article
    阳离子聚合材料和细胞穿透肽(CPP)通常用作核酸治疗剂评估中的递送载体。10-23DNAzyme是一种潜在的通过催化裂解疾病相关RNA的反义治疗剂。这里,评估了脂转染胺2000和Tat肽对10-23DNA酶催化活性的影响,根据观察到的速率常数,热稳定性,CD光谱,和PAGE分析,以模拟DNA酶底物的双链DNA作为对照。结果表明,阳离子载体对10-23DNA酶的催化性能有负面影响。重要的是,阳离子载体对双链体形成的不稳定作用值得注意,作为双链体的形成是反义和RNAi沉默机制的必要条件。
    Cationic polymeric materials and cell-penetrating peptides (CPPs) were often used as the delivery vectors in the evaluation of nucleic acid therapeutics. 10-23 DNAzyme is a kind of potential antisense therapeutics by catalytic cleavage of the disease-related RNAs. Here, lipofectamine 2000 and Tat peptide were evaluated for their effect on the catalytic activity of 10-23 DNAzyme, with the observed rate constant, thermal stability, CD spectra, and PAGE analysis, with a duplex DNA mimicking DNAzyme-substrate as a control. It was shown that the cationic carriers had a negative effect on the catalytic performance of the 10-23 DNAzyme. Significantly, the destabilizing effect of the cationic carriers on the duplex formation was noteworthy, as a duplex formation is an essential prerequisite in the silencing mechanisms of antisense and RNAi.
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  • 文章类型: Journal Article
    该方法论文提出了使用Rtm包进行科学文献文本挖掘的模板解决方案。可以使用本文提供的代码手动或自动收集要分析的文献。一旦文献被收集,进行文本挖掘的三个步骤可以如下所述执行:•加载和清除文章中的文本,•processing,统计分析,和聚类,和•使用广义和量身定制的可视化呈现结果。文本挖掘步骤可以应用于单个,多个,或文档的时间序列组。提供了对三篇已发表的同行评审文章的引用,这些文章使用了所介绍的文本挖掘方法。我们的方法的主要优点是:(1)它适用于研究和教育目的,(2)符合可察觉的可互操作和可复制(FAIR)原则,和(3)代码和示例数据在GitHub上根据开源ApacheV2许可证提供。
    This method paper presents a template solution for text mining of scientific literature using the R tm package. Literature to be analyzed can be collected manually or automatically using the code provided with this paper. Once the literature is collected, the three steps for conducting text mining can be performed as outlined below: •loading and cleaning of text from articles,•processing, statistical analysis, and clustering, and•presentation of results using generalized and tailor-made visualizations. The text mining steps can be applied to a single, multiple, or time series groups of documents. References are provided to three published peer reviewed articles that use the presented text mining methodology. The main advantages of our method are: (1) Its suitability for both research and educational purposes, (2) Compliance with the Findable Accessible Interoperable and Reproducible (FAIR) principles, and (3) Code and example data are made available on GitHub under the open-source Apache V2 license.
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  • 文章类型: Journal Article
    为了对抗COVID-19大流行,潜在的疗法已经以前所未有的速度开发并进入临床试验。一些最有希望的疗法是针对SARS-CoV-2的中和抗体。为了使这类中和抗体的治疗效果最大化,需要Fc工程化以调节效应子功能和延长半衰期。然而,至关重要的是,Fc工程不会对抗体的可显影性产生负面影响,由于这些属性在确保快速发展中起着关键作用,成功的制造,并提高了临床成功的总体机会。在这项研究中,我们描述了一组Fc工程(“TM-YTE”)SARS-CoV-2中和抗体的生物物理表征,与阿斯利康的Evushold(AZD7442;tixagevimab和西加维玛)中发现的Fc修饰相同,其中TM修饰(L234F/L235E/P331S)减少了与FcγR和C1q的结合,而YTE修饰(M252Y/S254T/T256E)延长了血清半衰期。我们先前已经表明,组合TM和YTEFc修饰两者可以降低CH2结构域的热稳定性,并且可能导致可显影性挑战。在这里我们展示,使用一组不同的TM-YTESARS-CoV-2中和抗体,尽管降低了FcCH2结构域的热稳定性,TM-YTE平台不具有任何固有的可发育性,并且在人FcRn转基因小鼠中显示出与充分表征的YTE平台相似的体内药代动力学特征。因此,TM-YTE是一种可开发的,效应器功能减少,半衰期延长抗体平台。
    To combat the COVID-19 pandemic, potential therapies have been developed and moved into clinical trials at an unprecedented pace. Some of the most promising therapies are neutralizing antibodies against SARS-CoV-2. In order to maximize the therapeutic effectiveness of such neutralizing antibodies, Fc engineering to modulate effector functions and to extend half-life is desirable. However, it is critical that Fc engineering does not negatively impact the developability properties of the antibodies, as these properties play a key role in ensuring rapid development, successful manufacturing, and improved overall chances of clinical success. In this study, we describe the biophysical characterization of a panel of Fc engineered (\"TM-YTE\") SARS-CoV-2 neutralizing antibodies, the same Fc modifications as those found in AstraZeneca\'s Evusheld (AZD7442; tixagevimab and cilgavimab), in which the TM modification (L234F/L235E/P331S) reduce binding to FcγR and C1q and the YTE modification (M252Y/S254T/T256E) extends serum half-life. We have previously shown that combining both the TM and YTE Fc modifications can reduce the thermal stability of the CH2 domain and possibly lead to developability challenges. Here we show, using a diverse panel of TM-YTE SARS-CoV-2 neutralizing antibodies, that despite lowering the thermal stability of the Fc CH2 domain, the TM-YTE platform does not have any inherent developability liabilities and shows an in vivo pharmacokinetic profile in human FcRn transgenic mice similar to the well-characterized YTE platform. The TM-YTE is therefore a developable, effector function reduced, half-life extended antibody platform.
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  • 文章类型: Journal Article
    将增加的稳定性工程化到抗体中可以改善它们的可显影性。虽然一系列属性需要优化,热稳定性和聚集是影响抗体产量的两个关键因素,纯度,以及整个开发和制造管道的特殊性。因此,一个理想的目标是早期应用蛋白质工程方法,例如与亲和力成熟平行,筛选出具有所需构象和胶体稳定性的潜在药物分子。本章介绍了我们的方法来计算表征抗体Fab片段,提出稳定的变体,然后通过实验验证这些预测。
    Engineering increased stability into antibodies can improve their developability. While a range of properties need to be optimized, thermal stability and aggregation are two key factors that affect the antibody yield, purity, and specificity throughout the development and manufacturing pipeline. Therefore, an ideal goal would be to apply protein engineering methods early-on, such as in parallel to affinity maturation, to screen out potential drug molecules with the desired conformational and colloidal stability. This chapter introduces our methods to computationally characterize an antibody Fab fragment, propose stabilizing variants, and then experimentally verify these predictions.
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  • 文章类型: Journal Article
    药物产品的所有起始材料和活性药物成分(API)必须进行分析鉴定(ID)测试,作为释放的一部分,然后将其引入药物制造过程。一般来说,这是优选的质量控制(QC)实验室进行ID测试使用简单和快速执行,但高度具体的分析方法。这种偏好也适用于寡核苷酸,一类新兴的API,其中应应用组合ID测试策略,包括完整的质量测定和序列特异性方法。在这项工作中,我们研究了在药物常规QC中,寡核苷酸的解链温度(Tm)的UV-光谱测定是否是这些物质的合适的序列特异性ID测试。因此,评估了该方法对偏离寡核苷酸序列的特异性。为此,设计了模型寡核苷酸序列及其变体,综合和分析,产生精确和具体的数据。甚至序列中的单碱基交换或单核苷酸缺失和插入也导致相应寡核苷酸双链体的测量Tm的显著变化。这些结果表明该方法对寡核苷酸序列的细微变化的一般高特异性,并且证实了分析方法作为药物QC环境中寡核苷酸的ID测试策略的一部分的适用性。
    All starting materials and the active pharmaceutical ingredient (API) of a drug product must be subjected to analytical identity (ID) testing as part of the release prior to their introduction into the pharmaceutical manufacturing process. Generally, it is preferable for Quality Control (QC) laboratories to perform ID tests using a simple and fast to perform, yet highly specific, analytical method. This preference also applies to oligonucleotides, an emerging class of APIs, where a combined ID testing strategy should be applied, including intact mass determination and a sequence-specific method. Within this work, we investigated whether ultravioloet (UV)-spectrometric determination of the melting temperature (Tm) of oligonucleotides is a suitable sequence-specific ID test for these substances in the pharmaceutical routine QC. Therefore, this method was evaluated for its specificity toward deviating oligonucleotide sequences. For this, model oligonucleotide sequences and variants thereof were designed, synthesized, and analyzed, resulting in precise and specific data. Even single base exchanges or single nucleotide deletions and insertions in the sequences led to significant changes in the measured Tm of the corresponding oligonucleotide duplexes. These results indicate a generally high specificity of the method toward subtle changes in oligonucleotide sequences and confirm the applicability of the analytical method as part of the ID testing strategy for oligonucleotides in the pharmaceutical QC environment.
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  • 文章类型: Journal Article
    背景:就单一疾病护理模式中的整体可行性和采用而言,远程监护(TM)的实施取得了成功。然而,现有研究的缺乏集中在护士主导的TM实施,该TM针对患有多种和复杂慢性疾病(CCC)的患者,阻碍了规模和传播到这些患者人群.特别是,对门诊CCC患者实施TM的临床观点知之甚少。
    目的:本研究旨在更好地了解临床团队(一线临床医生和行政职务人员)对护士主导的临床模式中复杂患者TM的实施和规范化的看法。
    方法:务实,进行了为期6个月的实施研究,以嵌入多条件TM,包括心力衰竭,高血压,糖尿病,成为护士主导的综合护理模式。在整个研究过程中,观察临床团队成员,并对这段时间提供的护理进行了图表审查。在研究结束时,临床团队成员参加了定性访谈,并完成了经调整的规范化测量开发问卷.归一化过程理论指导了演绎数据分析。
    结果:总体而言,9名团队成员参加了这项研究,作为TM计划的更大可行性研究的一部分,其中26例患者入组。团队成员对TM作为其实践中的干预措施的目的和价值有着共同的理解,以满足CCC患者的多样化需求。TM在几个方面与现有的慢性护理实践很好地吻合,但它改变了护理提供的过程(即,交互工作性子结构)。在护士主导的护理中有效的TM正常化需要重新思考临床工作流程以纳入TM,临床医生和患者之间的关系发展,与跨学科团队的沟通,和频繁的临床护理监督。这通过技能集可操作性的子结构得到了很好的体现,关系集成,规范化过程理论的语境整合。
    结论:临床医生成功地将TM应用到他们的日常实践中,因此一些提供者认为,如果没有TM,他们的角色将受到显着负面影响。这项研究表明,基于智能手机的TM系统在综合护士主导的护理模式中补充了照顾CCC患者的常规和具有挑战性的临床工作。
    The implementation of telemonitoring (TM) has been successful in terms of the overall feasibility and adoption in single disease care models. However, a lack of available research focused on nurse-led implementations of TM that targets patients with multiple and complex chronic conditions (CCC) hinders the scale and spread to these patient populations. In particular, little is known about the clinical perspective on the implementation of TM for patients with CCC in outpatient care.
    This study aims to better understand the perspective of the clinical team (both frontline clinicians and those in administrative positions) on the implementation and normalization of TM for complex patients in a nurse-led clinic model.
    A pragmatic, 6-month implementation study was conducted to embed multicondition TM, including heart failure, hypertension, and diabetes, into an integrated nurse-led model of care. Throughout the study, clinical team members were observed, and a chart review was conducted of the care provided during this time. At the end of the study, clinical team members participated in qualitative interviews and completed the adapted Normalization Measure Development questionnaires. The Normalization Process Theory guided the deductive data analysis.
    Overall, 9 team members participated in the study as part of a larger feasibility study of the TM program, of which 26 patients were enrolled. Team members had a shared understanding of the purpose and value of TM as an intervention embedded within their practice to meet the diverse needs of their patients with CCC. TM aligned well with existing chronic care practices in several ways, yet it changed the process of care delivery (ie, interactional workability subconstruct). Effective TM normalization in nurse-led care requires rethinking of clinical workflows to incorporate TM, relationship development between the clinicians and their patients, communication with the interdisciplinary team, and frequent clinical care oversight. This was captured well through the subconstructs of skill set workability, relational integration, and contextual integration of the Normalization Process Theory.
    Clinicians successfully adopted TM into their everyday practice such that some providers felt their role would be significantly and negatively affected without TM. This study demonstrated that smartphone-based TM systems complemented the routine and challenging clinical work caring for patients with CCC in an integrated nurse-led care model.
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