dose reduction

剂量减少
  • 文章类型: Case Reports
    背景:BrentuximabVedotin(BV)彻底改变了霍奇金淋巴瘤的治疗前景,然而,它对先前存在的自身免疫性疾病的影响仍然难以捉摸。方法:这里,我们介绍了4例并发自身免疫性疾病的患者-克罗恩病,白癜风,I型糖尿病,和微小变化疾病-接受BV治疗霍奇金淋巴瘤。由于具有高IPI评分的晚期疾病,患者用A-AVD代替ABVD治疗。结果:我们的发现揭示了BV暴露与自身免疫表现之间令人惊讶和复杂的相互作用,强调在患者管理中需要多学科合作。值得注意的是,在T细胞介导的自身免疫占优势的前3例病例中观察到自身免疫症状加重.此外,BV暴露导致白癜风患者自身免疫性血小板减少症,强调了免疫调节的深刻破坏。相反,在微小变化的疾病案例中,一种以B细胞和T细胞介导的免疫混合为特征的疾病,结果是有利的。结论:本文强调了在并发自身免疫性疾病的患者中,对BV引起的自身免疫性发作保持警惕的重要性。为量身定制的患者护理提供见解。
    Background: Brentuximab Vedotin (BV) has revolutionized the treatment landscape for Hodgkin\'s lymphoma, yet its effects on pre-existing autoimmune disorders remain elusive. Methods: Here, we present four cases of patients with concurrent autoimmune conditions-Crohn\'s disease, vitiligo, type I diabetes, and minimal change disease-undergoing BV therapy for Hodgkin\'s lymphoma. The patients were treated with A-AVD instead of ABVD due to advanced-stage disease with high IPI scores. Results: Our findings reveal the surprising and complex interplay between BV exposure and autoimmune manifestations, highlighting the need for multidisciplinary collaboration in patient management. Notably, the exacerbation of autoimmune symptoms was observed in the first three cases where T-cell-mediated autoimmunity predominated. Additionally, BV exposure precipitated autoimmune thrombocytopenia in the vitiligo patient, underscoring the profound disruptions in immune regulation. Conversely, in the minimal change disease case, a disease characterized by a blend of B- and T-cell-mediated immunity, the outcome was favorable. Conclusions: This paper underscores the critical importance of vigilance toward autoimmune flare-ups induced by BV in patients with concurrent autoimmune conditions, offering insights for tailored patient care.
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  • 文章类型: Case Reports
    背景:80%的患者将有关治疗方案的信息视为康复的重要组成部分,此外,有精神病发作史的患者感到被排除在抗精神病药物治疗的决策之外,最重要的是,精神卫生工作人员倾向于不愿意支持精神分裂症患者的共同决策和药物逐渐减少。本病例系列旨在证明抗精神病药物的逐渐减少,以及引导逐渐减少如何影响患者的自主性和精神康复。
    方法:我们介绍了6名诊断为精神分裂症的患者(国际精神和行为障碍分类-第10版代码F20.0-5,F20.7-9),他们在我们的诊所接受了专业指导的逐渐减少。该诊所旨在指导患者在安全的环境中确定最低剂量的抗精神病药物,以最大程度地减少严重复发的风险。两名患者完全停止了抗精神病药物治疗,两个人在逐渐缩小期间复发,一个人选择以低剂量停止渐缩,和一名患有难治性精神分裂症的患者,它仍在逐渐缩小。
    结论:减少抗精神病药物剂量可提高某些患者的情绪意识(n=4),帮助他们制定更好的策略来应对压力并增加康复感。在逐渐减少的过程中,患者感受到了更大的自主权和赋权感,即使停药是不可能的。提高患者的意识和在复发期间的早期干预可以防止严重复发。
    一些精神分裂症患者可能过度用药,导致不必要的副作用和减少用药的愿望。我们研究中的患者说明了与患者共同进行的抗精神病药物的指导逐渐减少如何改善情绪意识并制定有效的症状管理策略。这反过来可能会导致更大的赋权和认同感,并赋予生活更多的意义,支持个人康复的经验。
    BACKGROUND: 80% of patients value information on treatment options as an important part of recovery, further patients with a history of psychotic episodes feel excluded from decision making about their antipsychotic treatment, and on top of that, mental health staff is prone to be reluctant to support shared decision making and medication tapering for patients with schizophrenia. This case series aims to demonstrate the tapering of antipsychotic medication and how guided tapering affects the patient\'s feeling of autonomy and psychiatric rehabilitation.
    METHODS: We present six patients diagnosed with schizophrenia (International Classification of Mental and Behavioral Disorders- 10th Edition codes F20.0-5, F20.7-9) who underwent professionally guided tapering in our clinic. The clinic aims to guide the patients to identify the lowest possible dose of antipsychotic medication in a safe setting to minimise the risk of severe relapse. Two patients completely discontinued their antipsychotic medication, two suffered a relapse during tapering, one chose to stop the tapering at a low dose, and one patient with treatment resistant schizophrenia, which is still tapering down.
    CONCLUSIONS: Reducing the antipsychotic dose increased emotional awareness in some patients (n = 4) helping them to develop better strategies to handle stress and increased feelings of recovery. Patients felt a greater sense of autonomy and empowerment during the tapering process, even when discontinuation was not possible. Increased awareness in patients and early intervention during relapse may prevent severe relapse.
    UNASSIGNED: Some patients with schizophrenia might be over medicated, leading to unwanted side effects and the wish to reduce their medication. The patients in our study illustrate how guided tapering of antipsychotic medication done jointly with the patient can lead to improved emotional awareness and the development of effective symptom management strategies. This may in turn lead to a greater sense of empowerment and identity and give life more meaning, supporting the experience of personal recovery.
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  • 文章类型: Journal Article
    背景:Elexacaftor/tezacaftor/ivacaftor(ETI)治疗与囊性纤维化(pwCF)患者的肺功能显着改善有关;然而,一些患者出现不良反应(AE),包括肝毒性.一种潜在的策略是降低ETI的剂量,目的是维持治疗功效,同时解决AE。我们报告了我们在ETI治疗后出现AE的个体中剂量减少的经验。我们通过探索预测的肺暴露和潜在的药代动力学-药效学(PK-PD)关系,为ETI剂量减少提供了机制支持。
    方法:本病例系列包括因AEs导致剂量减少的ETI处方成人,收集他们预测的1s用力呼气量(ppFEV1)和自我报告的呼吸道症状的百分比。建立了完整的基于生理的药代动力学(PBPK)模型,并结合了生理信息和药物依赖性参数。根据可用的药代动力学和剂量反应关系数据验证模型。然后使用模型来预测稳态下的ETI的肺浓度。
    结果:15例患者因不良事件接受ETI剂量减少。在所有患者中观察到剂量减少后ppFEV1没有显著变化的临床稳定性。15例中有13例发生了AE的消退或改善。减少剂量ETI的模型预测的肺浓度超过了体外氯化物转运测量中报告的最大有效浓度(EC50)的一半,提供了一个假设,为什么治疗功效得以维持。
    结论:尽管在少数患者中,这项研究提供的证据表明,在经历AE的pwCF中减少ETI剂量可能是有效的.PBPK模型能够通过模拟ETI的靶组织浓度来探索该发现的机理基础,所述浓度可以与体外药物功效进行比较。
    Elexacaftor/tezacaftor/ivacaftor (ETI) treatment is associated with significant improvement in lung function in people with cystic fibrosis (pwCF); however, some patients experience adverse effects (AEs) including hepatotoxicity. One potential strategy is dose reduction in ETI with the goal of maintaining therapeutic efficacy while resolving AEs. We report our experience of dose reduction in individuals who experienced AEs following ETI therapy. We provide mechanistic support for ETI dose reduction by exploring predicted lung exposures and underlying pharmacokinetics-pharmacodynamics (PK-PD) relationships.
    Adults prescribed ETI who underwent dose reduction due to the AEs were included in this case series, and their percent predicted forced expiratory volume in 1 s (ppFEV1 ) and self-reported respiratory symptoms were collected. The full physiologically based pharmacokinetic (PBPK) models of ETI were developed incorporating physiological information and drug-dependent parameters. The models were validated against available pharmacokinetic and dose-response relationship data. The models were then used to predict lung concentrations of ETI at steady-state.
    Fifteen patients underwent dose reduction in ETI due to AEs. Clinical stability without significant changes in ppFEV1 after dose reduction was observed in all patients. Resolution or improvement of AEs occurred in 13 of the 15 cases. The model-predicted lung concentrations of reduced dose ETI exceeded the reported half maximal effective concentration (EC50 ) from measurement of in vitro chloride transport, providing a hypothesis as to why therapeutic efficacy was maintained.
    Albeit in a small number of patients, this study provides evidence that reduced ETI doses in pwCF who have experienced AEs may be effective. The PBPK models enable exploration of a mechanistic basis for this finding by simulating target tissue concentrations of ETI that can be compared with drug efficacy in vitro.
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  • 文章类型: Journal Article
    背景:为了确定与标准注射剂量相比,人工智能(AI)处理的PET/CT图像是否减少了18-F-FDG活性的三分之一,不劣于原生扫描,如果是,评估商业化的潜在影响。
    方法:SubtlePET™AI被引入意大利的PET/CT中心。前瞻性纳入符合18F-FDGPET/CT标准的患者。施用的18F-FDG减少到标准剂量的三分之二。患者接受了一次低剂量CT和两次顺序PET扫描;“PET处理”,剂量减少,采集时间标准,和“PET-native”,带有模拟标准采集时间和剂量的经过时间。使用SubtlePET™重建PET处理的图像。PET天然图像被定义为参考标准。数据集是匿名化的,并由四个盲人读者以随机顺序独立评估。评估包括主观图像质量(IQ)评估,病变可检测性,和商业利益评估。
    结果:从2020年2月至4月,有61例患者被前瞻性纳入。所有扫描仪模型的主观智商在数据集(4.62±0.23,p=0.237)之间没有显着差异,与“几乎完美”的读者之间的协议。病变可检测性数据集之间没有显著差异,目标病变平均SUVmax值,和肝脏平均SUV平均值(182.75/181.75[SD:0.71],9.8/11.4[标准差:1.13],2.1/1.9[标准差:0.14])。在PET处理的检查中没有报告假阳性病变。每次检查商定的SubtlePET™价格为FDG节省的15-20%。
    结论:这是第一个真实的研究,以证明AI处理的18F-FDGPET/CT检查具有66%标准剂量和定义方法的非劣效性AI解决方案价格。
    BACKGROUND: To determine whether artificial intelligence (AI) processed PET/CT images of reduced by one-third of 18-F-FDG activity compared to the standard injected dose, were non-inferior to native scans and if so to assess the potential impact of commercialization.
    METHODS: SubtlePET™ AI was introduced in a PET/CT center in Italy. Eligible patients referred for 18F-FDG PET/CT were prospectively enrolled. Administered 18F-FDG was reduced to two-thirds of standard dose. Patients underwent one low-dose CT and two sequential PET scans; \"PET-processed\" with reduced dose and standard acquisition time, and \"PET-native\" with an elapsed time to simulate standard acquisition time and dose. PET-processed images were reconstructed using SubtlePET™. PET-native images were defined as the standard of reference. The datasets were anonymized and independently evaluated in random order by four blinded readers. The evaluation included subjective image quality (IQ) assessment, lesion detectability, and assessment of business benefits.
    RESULTS: From February to April 2020, 61 patients were prospectively enrolled. Subjective IQ was not significantly different between datasets (4.62±0.23, p=0.237) for all scanner models, with \"almost perfect\" inter-reader agreement. There was no significant difference between datasets in lesions\' detectability, target lesion mean SUVmax value, and liver mean SUVmean value (182.75/181.75 [SD:0.71], 9.8/11.4 [SD:1.13], 2.1/1.9 [SD:0.14] respectively). No false-positive lesions were reported in PET-processed examinations. Agreed SubtlePET™ price per examination was 15-20% of FDG savings.
    CONCLUSIONS: This is the first real-world study to demonstrate the non-inferiority of AI processed 18F-FDG PET/CT examinations obtained with 66% standard dose and a methodology to define the AI solution price.
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  • 文章类型: Journal Article
    OBJECTIVE: The purpose of this study was to determine if CT for appendicitis can be abbreviated to begin at the top of the L2 vertebral body level and still maintain the detection rate of appendicitis and other symptomatic pathology without omitting significant incidental findings.
    METHODS: Retrospective review of CT abdomen-pelvis exams for suspected appendicitis over a 5-month period was performed. The Z-axis scan length of the original full scans and theoretical limited scans from the top of L2 were recorded and calculated. Images were reviewed for incidental findings above the L2 vertebral body level and categorized by severity per American College of Radiology (ACR) white paper guidelines. Final diagnoses based on imaging findings were also recorded.
    RESULTS: One hundred nineteen patients (46 males, 73 females, mean age 29 ± 14) were included. Appendicitis was present in 26 cases (22%). Using a theoretical scan beginning at the top of the L2 vertebral body, none of the findings leading to diagnosis of appendicitis would have been missed. A total of 30 incidental findings were found above the L2 vertebral body. Per ACR white paper guidelines, 26 of these findings did not require additional imaging follow-up. Additional follow-up imaging was recommended for 3 of the findings above L2, and 1 right adrenal metastasis was found above L2 in a patient with previously undiagnosed NSCLC. This patient coincidentally also had appendicitis. No symptomatic pathology would have been missed had the scans begun at the top of the L2 vertebral body. Such an abbreviated scan would have resulted in a mean Z-axis reduction of 12.9 cm (30.3%).
    CONCLUSIONS: CT using abbreviated Z-axis scan length can reduce radiation dose and provide necessary imaging needed to diagnose appendicitis or other symptomatic pathology without omitting significant incidental findings.
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  • 文章类型: Journal Article
    Epidermal growth factor receptor (EGFR) mutation is a favorable prognostic factor of non-small cell lung cancer (NSCLC). In the majority of patients with EGFR mutations, clinical benefits of EGFR-tyrosine kinase inhibitors (TKIs) have been reported. One of the TKIs, gefitinib, appears to be less toxic to the skin than other TKIs. The present study reports a case of NSCLC with EGFR mutation (exon 19 deletion) in which dose-reduced gefitinib was effective against recurrence. Due to development of a grade 3 skin adverse event (AE) after 2 months of daily administration of gefitinib, the frequency of administration of gefitinib was reduced to every other day for 2 weeks. As the AE continued, the frequency of administration was reduced to once every 3 days. The patient has been in remission for 27 months since treatment with 250 mg gefitinib once every 3 days was initiated, which is the lowest dose to be reported in a successfully treated case of NSCLC with EGFR mutation. Dose reduction of gefitinib might be appropriate for patients with severe AEs and should be considered as a treatment option after 1 or 2 months of regular daily dosing of gefitinib if there is no other satisfactory treatment option.
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