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Schematic Suggestion and Results of Two-Layer Coating System for Controlling Corrosional Toxicity of Titanium Dioxide from Dental Implant Fixture 控制种植牙固定物中二氧化钛腐蚀毒性的双层涂层系统的原理建议和结果
Pub Date : 2021-01-01 DOI: 10.2139/ssrn.3898489
Bon-Suk Goo, T. Navrátil, I. Malbohan
Introduction: Titanium dioxide has been classified by the International Agency for Research on Cancer (IARC) as a Group 2B carcinogen. As indispensable material for dental implant fixture, dental patients are exposed to its toxicological reactions. Objectives: The primary aim of this research is to prevent making nanoparticle titanium dioxide from the corrosion of dental implant fixture and gain possible osseointegration. Methods: The authors introduce two-layer coating system for controlling corrosional toxicity of TiO2 from the surface of two dental implant fixtures by medronic acid and teriparatide acetate. Results: The first layer coated with medronic acid will generate phosphate bridges, functioning as a corrosion-resistant sheath layer, and will be the only connector to Forteo (Teriparatide Acetate). The second layer encloses the essential elements of teriparatide like C, N, O and H with saving the functional radicals like CNO-, C2H3O-, CHO2-, C3H3O- and C2H3O2-, for and it will stimulate the coated implant fixture with PTH receptors, osteoblasts, and osteogenesis. The first layer covers Ti-O-P, acting as a titanium grade 4 antioxidant. Conclusion: The top surface radicals in the second layer of the fixture have pharmaceutically functioning parts of the chemical structure of Teriparatide (C181H291N55O51S2) activating osteoblasts more than osteoclasts, which leads to an overall increase in bone. Though the recommended duration of use for grade 4 implant fixtures is 3 years, but these new coated fixtures are expected to use longer than 3 years by containing the stimulating effect of new alveolar bone formation by increasing the mineral density of the alveolar bone around the fixture besides preventing corrosional toxicity from the surface of preexisting titanium fixtures. Cheaper producing cost of a coated implant fixture are also suggested.
简介:二氧化钛已被国际癌症研究机构(IARC)列为2B类致癌物。作为种植牙固定物不可缺少的材料,其毒理学反应是牙科患者的直接暴露。目的:本研究的主要目的是防止纳米二氧化钛在种植体固定物的腐蚀中产生,并获得可能的骨整合。方法:采用美地膦酸和醋酸特立帕肽两层涂层体系,控制两种种植体固定物表面TiO2的腐蚀毒性。结果:第一层涂覆美地膦酸将产生磷酸盐桥,作为耐腐蚀的护套层,并将成为Forteo (Teriparatide Acetate)的唯一连接器。第二层包裹着特立帕肽的基本元素,如C、N、O和H,保留了功能自由基,如CNO-、c2h30 -、CHO2-、c3h30 -和C2H3O2-,并刺激PTH受体、成骨细胞和成骨。第一层覆盖Ti-O-P,作为钛级4抗氧化剂。结论:第二层治具的顶表面自由基具有特立帕肽(C181H291N55O51S2)化学结构的药理功能部分,对成骨细胞的激活作用大于破骨细胞,导致骨整体增加。虽然4级种植固定物的推荐使用时间为3年,但这些新的涂层固定物除了可以防止已有钛固定物表面的腐蚀毒性外,还可以通过增加固定物周围牙槽骨的矿物质密度来抑制新牙槽骨形成的刺激作用,预计使用时间将超过3年。同时提出了采用涂层种植固定装置降低生产成本的方法。
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引用次数: 0
Towards Adaptive Robust Radiotherapy to Manage Radioresistance 迈向自适应稳健放射治疗以管理放射抵抗
Pub Date : 2020-12-03 DOI: 10.2139/ssrn.3836102
A. Roy, S. Dabadghao, Ahmadreza Marandi
In radiotherapy, uncertainties in tumor radioresistance and its progression can degrade the efficacy of deterministic treatments. While a robust methodology can overcome this, it often produces overly conservative or suboptimal decisions, especially when there are changes in time. We aim to develop an adaptive radiotherapy planning framework that can reduce over-conservatism yet remain robust to the uncertainties in radioresistance. Specifically, intermediate imaging is used to update the uncertainty at each stage and curb over-conservatism. While additional imaging reduces uncertainty, it accrues costs such as extra radiation to organs, which deters continuous imaging. We probe this trade-off in uncertainty and cost of observation by computing and comparing results from two-stage, three-stage, and four-stage robust models. The three robust models are also compared to two currently practiced deterministic methods, one that does not account for radioresistance and one that assumes a constant radioresistance. All five models are evaluated on a clinical prostate case. The three robust models improve control of the tumor compared to the deterministic model ignoring radioresistance, at comparable radiation dose to critical organs. The robust models also reduce tumor overdose and organ dose compared to the deterministic model assuming a constant radioresistance. Increasing the number of intermediate imaging leads to further improvements, especially on tumor dose criteria under best-case and nominal scenarios. Under the worst-case, intermediate images provide no additional benefit as robust optimization inherently protects against the worst-case. The proposed method is generic and can include additional sources of uncertainties that reduce the effect of radiation.
在放疗中,肿瘤放射耐药及其进展的不确定性会降低确定性治疗的疗效。虽然健壮的方法可以克服这一点,但它通常会产生过于保守或次优的决策,特别是当时间发生变化时。我们的目标是开发一种自适应放疗计划框架,可以减少过度保守,但对放射抗性的不确定性保持稳健。具体而言,中间成像用于更新每个阶段的不确定度并抑制过度保守性。虽然额外的成像减少了不确定性,但它增加了成本,如对器官的额外辐射,这阻碍了连续成像。我们通过计算和比较两阶段、三阶段和四阶段鲁棒模型的结果来探讨这种不确定性和观察成本的权衡。还将这三种稳健模型与目前采用的两种确定性方法进行了比较,一种不考虑辐射阻力,另一种假设辐射阻力恒定。所有五种模式评估了临床前列腺病例。与忽略放射耐药的确定性模型相比,在对关键器官的相当辐射剂量下,这三种鲁棒模型改善了对肿瘤的控制。与假设恒定辐射阻力的确定性模型相比,鲁棒模型还减少了肿瘤过量和器官剂量。增加中间成像的次数会导致进一步的改善,特别是在最佳情况和名义情况下的肿瘤剂量标准。在最坏情况下,中间图像没有提供额外的好处,因为鲁棒优化本身就可以防止最坏情况的发生。所提出的方法是通用的,可以包括减少辐射影响的其他不确定源。
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引用次数: 0
Distribution and Prognosis of Metastatic Disease in Newly Diagnosed Stage IV Breast Cancer 新诊断的IV期乳腺癌转移灶的分布及预后
Pub Date : 2020-02-23 DOI: 10.2139/ssrn.3633992
X. Kong, Qiang Liu, R. Coleman, Yi Fang, Jing Wang
Background Thorough population-based estimates of the epidemiological features of metastatic disease in newly diagnosed stage IV breast cancer are lacking.

Methods Target patients were identified using the Surveillance, Epidemiology, and End Results (SEER) database. Logistic regression was used to estimate the odds ratios (ORs) for different metastasis patterns (bone, brain, liver and lung), stratified by sociodemographic and clinicopathological variables. Survival estimates were performed using the Kaplan-Meier method and the Cox regression.

Results A total of 356789 patients with breast cancer were included of which 18036 (5.06%) had stage IV disease. Bone metastasis had the highest composition ratio (42.6%). Patients with HR-/HER2+ subtype had the highest metastasis at diagnosis incidence proportions (1310/15062 [8.7%] of the entire cohort). Female breast cancer patients were more susceptible to bone metastasis, lung metastasis, and liver metastasis than male patients (all P<0.01). Hispanics were the most likely to have brain metastases (P<0.01). Compared with other subtypes, HR-/HER2- patients was the most likely to have lung metastases. Patients with bone metastasis displayed the longest median survival (27 months). Among patients with brain or liver metastases, Grade III patients had the worst prognosis (P<0.01). Among patients with lung metastasis, infiltrating duct mixed with other types of carcinoma (IDM) had a better prognosis than infiltrating duct carcinoma (IDC) (P<0.01). For liver metastases, TNM N0 stage patients had the highest risk of death, followed by N2 (P<0.01).

Conclusion We believe this is the most comprehensive analysis of the distribution and prognosis of metastatic disease in newly diagnosed stage IV breast cancer. It lends support to consideration of further studies evaluating the utility of modern screening strategies of the bone, brain, liver and lung among patient subsets at high risk for metastasis.
背景对新诊断的IV期乳腺癌转移性疾病的流行病学特征缺乏全面的基于人群的估计。方法使用监测、流行病学和最终结果(SEER)数据库确定目标患者。采用Logistic回归估计不同转移模式(骨、脑、肝和肺)的优势比(ORs),并按社会人口统计学和临床病理变量分层。使用Kaplan-Meier法和Cox回归进行生存估计。结果共纳入356789例乳腺癌患者,其中ⅳ期18036例(5.06%)。骨转移的构成比例最高(42.6%)。HR-/HER2+亚型患者在诊断时的转移发生率最高(占整个队列的1310/15062[8.7%])。女性乳腺癌患者更易发生骨转移、肺转移和肝转移(p < 0.01)。西班牙裔患者发生脑转移的可能性最大(P<0.01)。与其他亚型相比,HR-/HER2-患者最容易发生肺转移。骨转移患者的中位生存期最长(27个月)。在脑或肝转移患者中,III级患者预后最差(P<0.01)。在肺转移患者中,浸润性导管混合其他类型癌(IDM)预后优于浸润性导管癌(IDC) (P<0.01)。对于肝转移,TNM N0期患者死亡风险最高,N2期次之(P<0.01)。结论我们认为这是对新诊断的IV期乳腺癌转移灶分布和预后最全面的分析。它支持进一步研究评估骨、脑、肝和肺的现代筛查策略在转移高风险患者亚群中的效用。
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引用次数: 0
Preventative Cancer Treatments Through Optimizing Tissue Structure 通过优化组织结构来预防癌症
Pub Date : 2020-02-10 DOI: 10.2139/ssrn.3542732
C. Graser
The likelihood of cancer emergence is highly dependent on the underlying tissue structure. This article gives evolutionary explanations for why natural selection fails to select for tissue structures that would minimize the likelihood of cancer. In a second step, a mathematical framework is proposed, within which the risk of cancer emergence can be expressed and calculated dependent on a given tissue structure. This can be used to identify optimal structures and strategies for improvement. Lastly, the article explores both, ways to identify target areas for such intervention, as well as avenues towards developing treatment options.
癌症发生的可能性高度依赖于潜在的组织结构。这篇文章从进化论的角度解释了为什么自然选择不能选择使癌症可能性最小化的组织结构。在第二步中,提出了一个数学框架,在这个框架中,癌症发生的风险可以根据给定的组织结构来表达和计算。这可以用来确定最优的结构和改进策略。最后,本文探讨了确定此类干预目标区域的方法,以及开发治疗方案的途径。
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引用次数: 0
Bioengineered Cancer-Fibroblast Interactions in Patient-Derived Colorectal Cancer Organoid Models 生物工程癌症成纤维细胞在患者来源的结肠直肠癌类器官模型中的相互作用
Pub Date : 2020-01-01 DOI: 10.2139/ssrn.3687917
Xiaobei Luo, E. Fong, Chaojun Zhu, Quy Xiao Xuan Lin, Man Xiong, Aimin Li, Tingting Li, T. Benoukraf, Hanry Yu, Side Liu
The development of patient-derived organoid (PDO) technologies has greatly expanded the toolbox for drug discovery and personalized drug screening for several cancer types. While PDO models more closely represent the molecular characteristics and heterogeneity of patient tumors than traditional immortalized cancer cell lines, they are inherently limited in their ability to reflect the tumor microenvironment in vitro as they comprise exclusively of epithelial cells. The lack of stromal cells in PDO models, such as cancer-associated fibroblasts (CAFs), poses a major problem as these tumor microenvironmental components contribute to the various hallmarks of cancer and response to therapy. Particularly for colorectal cancer, CAFs comprise the majority of the tumor microenvironment and play important roles in cancer progression and drug resistance. In this study, we addressed this problem by establishing in vitro conditions that robustly enable the co-culture of CRC PDO with patient-derived CAFs. We report the development of an engineered tumor microenvironment consisting of CRC PDO encapsulated within a well-defined three-dimensional (3D) hyaluronan-gelatin hydrogel and co-cultured with patient-derived CAFs. Basement membrane extracts conventionally used for PDO culture exhibit batch-to-batch variability. Considering that the CRC extracellular matrix is high in hyaluronan and collagen I, and that hyaluronan-based matrices have been shown to be conducive for the culture of various human cancers, we hypothesized that hyaluronan-gelatin hydrogels may serve as a suitable alternative 3D matrix to support the co-culture of CRC PDO and CAFs. Through RNA- and whole-exome sequencing, we first show that these hydrogels are capable of maintaining key molecular characteristics of the original patient tumors in CRC PDO but not support the culture of CAFs. Further, based on our findings that CRC PDO culture medium poorly supports CAF viability, we developed a co-culture strategy that maintains the viability of both CRC PDO and CAFs. We found that in the absence of growth factors added to the co-culture, CAFs were able to maintain the proliferation of the cultured CRC PDO in the hydrogels and restore distinct biological pathways absent in the PDO culture alone but present in patient tissues. Lastly, we demonstrate that these CRC PDO-CAFs models are suitable for evaluating standard-of-care drugs, making them potentially very useful for realizing personalized cancer medicine.
患者源性类器官(PDO)技术的发展极大地扩展了针对几种癌症类型的药物发现和个性化药物筛选的工具箱。虽然PDO模型比传统的永生化癌细胞系更能代表患者肿瘤的分子特征和异质性,但由于它们仅由上皮细胞组成,因此在体外反映肿瘤微环境的能力上存在固有的局限性。PDO模型中缺乏基质细胞,如癌症相关成纤维细胞(CAFs),这是一个主要问题,因为这些肿瘤微环境成分有助于癌症的各种特征和对治疗的反应。特别是在结直肠癌中,CAFs构成了肿瘤微环境的大部分,在癌症进展和耐药中发挥着重要作用。在这项研究中,我们通过建立体外条件来解决这个问题,该条件可以使CRC PDO与患者来源的CAFs共同培养。我们报道了一种工程肿瘤微环境的发展,该微环境由CRC PDO封装在明确定义的三维(3D)透明质酸-明胶水凝胶中,并与患者来源的CAFs共培养。通常用于PDO培养的基膜提取物表现出批次间的可变性。考虑到结直肠癌细胞外基质富含透明质酸和胶原I,并且基于透明质酸的基质已被证明有利于各种人类癌症的培养,我们假设透明质酸明胶水凝胶可以作为一种合适的替代3D基质来支持结直肠癌PDO和CAFs的共培养。通过RNA和全外显子组测序,我们首次发现这些水凝胶能够维持CRC PDO中原始患者肿瘤的关键分子特征,但不支持CAFs的培养。此外,基于我们的研究结果,CRC PDO培养基不支持CAF的活力,我们开发了一种维持CRC PDO和CAF活力的共培养策略。我们发现,在共培养中没有添加生长因子的情况下,CAFs能够维持水凝胶中培养的CRC PDO的增殖,并恢复PDO单独培养中缺失的、但存在于患者组织中的独特生物途径。最后,我们证明了这些CRC PDO-CAFs模型适用于评估标准护理药物,使它们对实现个性化癌症药物非常有用。
{"title":"Bioengineered Cancer-Fibroblast Interactions in Patient-Derived Colorectal Cancer Organoid Models","authors":"Xiaobei Luo, E. Fong, Chaojun Zhu, Quy Xiao Xuan Lin, Man Xiong, Aimin Li, Tingting Li, T. Benoukraf, Hanry Yu, Side Liu","doi":"10.2139/ssrn.3687917","DOIUrl":"https://doi.org/10.2139/ssrn.3687917","url":null,"abstract":"The development of patient-derived organoid (PDO) technologies has greatly expanded the toolbox for drug discovery and personalized drug screening for several cancer types. While PDO models more closely represent the molecular characteristics and heterogeneity of patient tumors than traditional immortalized cancer cell lines, they are inherently limited in their ability to reflect the tumor microenvironment in vitro as they comprise exclusively of epithelial cells. The lack of stromal cells in PDO models, such as cancer-associated fibroblasts (CAFs), poses a major problem as these tumor microenvironmental components contribute to the various hallmarks of cancer and response to therapy. Particularly for colorectal cancer, CAFs comprise the majority of the tumor microenvironment and play important roles in cancer progression and drug resistance. In this study, we addressed this problem by establishing in vitro conditions that robustly enable the co-culture of CRC PDO with patient-derived CAFs. We report the development of an engineered tumor microenvironment consisting of CRC PDO encapsulated within a well-defined three-dimensional (3D) hyaluronan-gelatin hydrogel and co-cultured with patient-derived CAFs. Basement membrane extracts conventionally used for PDO culture exhibit batch-to-batch variability. Considering that the CRC extracellular matrix is high in hyaluronan and collagen I, and that hyaluronan-based matrices have been shown to be conducive for the culture of various human cancers, we hypothesized that hyaluronan-gelatin hydrogels may serve as a suitable alternative 3D matrix to support the co-culture of CRC PDO and CAFs. Through RNA- and whole-exome sequencing, we first show that these hydrogels are capable of maintaining key molecular characteristics of the original patient tumors in CRC PDO but not support the culture of CAFs. Further, based on our findings that CRC PDO culture medium poorly supports CAF viability, we developed a co-culture strategy that maintains the viability of both CRC PDO and CAFs. We found that in the absence of growth factors added to the co-culture, CAFs were able to maintain the proliferation of the cultured CRC PDO in the hydrogels and restore distinct biological pathways absent in the PDO culture alone but present in patient tissues. Lastly, we demonstrate that these CRC PDO-CAFs models are suitable for evaluating standard-of-care drugs, making them potentially very useful for realizing personalized cancer medicine.","PeriodicalId":19714,"journal":{"name":"Oncology eJournal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81297883","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
Mammography: Case Histories of Significant Medical Advances 乳房x光检查:重大医学进展的病例史
Pub Date : 2019-07-19 DOI: 10.2139/SSRN.3424129
A. Bhide, S. Datar, K. Stebbins
We describe how the development of x-ray-based techniques and equipment (“mammography”) lead to widespread screening for breast cancer and enabled “minimally invasive” biopsies of breast tumors. Specifically, we chronicle how: 1) new protocols and equipment catalyzed the first widespread screening programs and minimally invasive biopsies in the 1960s and 1970s; 2) concerns about safety and accuracy spurred technological advance in the 1980s; and, 3) digitization further improved the safety and accuracy of mammography in the 1990s and 2000s.
我们描述了基于x射线的技术和设备(“乳房x光摄影”)的发展如何导致乳腺癌的广泛筛查,并使乳腺肿瘤的“微创”活检成为可能。具体来说,我们记录了:1)在20世纪60年代和70年代,新的方案和设备催化了第一次广泛的筛查项目和微创活检;2) 20世纪80年代,对安全性和准确性的担忧刺激了技术进步;3)数字化在20世纪90年代和21世纪初进一步提高了乳房x光检查的安全性和准确性。
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引用次数: 3
Identification of Cancer: Mesothelioma’s Disease Using Logistic Regression and Association Rule 使用逻辑回归和关联规则识别癌症:间皮瘤疾病
Pub Date : 2018-12-02 DOI: 10.3844/ajeassp.2018.1310.1319
Avishek Choudhury
Malignant Pleural Mesothelioma (MPM) or malignant mesothelioma (MM) is an atypical, aggressive tumor that matures into cancer in the pleura, a stratum of tissue bordering the lungs. Diagnosis of MPM is difficult and it accounts for about seventy-five percent of all mesothelioma diagnosed yearly in the United States of America. Being a fatal disease, early identification of MPM is crucial for patient survival. Our study implements logistic regression and develops association rules to identify early stage symptoms of MM. We retrieved medical reports generated by Dicle University and implemented logistic regression to measure the model accuracy. We conducted (a) logistic correlation, (b) Omnibus test and (c) Hosmer and Lemeshow test for model evaluation. Moreover, we also developed association rules by confidence, rule support, lift, condition support and deployability. Categorical logistic regression increases the training accuracy from 72.30% to 81.40% with a testing accuracy of 63.46%. The study also shows the top 5 symptoms that is mostly likely indicates the presence in MM. This study concludes that using predictive modeling can enhance primary presentation and diagnosis of MM.
恶性胸膜间皮瘤(Malignant Pleural Mesothelioma, MPM)或恶性间皮瘤(Malignant Mesothelioma, MM)是一种非典型的侵袭性肿瘤,在胸膜(与肺交界的组织层)成熟为癌症。MPM的诊断是困难的,它占美国每年诊断的所有间皮瘤的75%。作为一种致命的疾病,早期发现对患者的生存至关重要。我们的研究采用逻辑回归并开发关联规则来识别MM的早期症状。我们检索了Dicle大学生成的医学报告,并采用逻辑回归来衡量模型的准确性。我们对模型进行了(a) logistic相关,(b) Omnibus检验和(c) Hosmer and Lemeshow检验。此外,我们还通过置信度、规则支持、提升、条件支持和可部署性开发了关联规则。分类逻辑回归将训练准确率从72.30%提高到81.40%,测试准确率为63.46%。该研究还显示了最可能提示MM存在的前5种症状。本研究得出结论,使用预测模型可以增强MM的原发性表现和诊断。
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引用次数: 15
The Effects of Cost Sharing on Cancer Screening and Price Shopping: Evidence from the Affordable Care Act 费用分摊对癌症筛查和价格购物的影响:来自平价医疗法案的证据
Pub Date : 2018-07-01 DOI: 10.2139/ssrn.3264607
C. Whaley
Colorectal cancer is the second leading cause of cancer-related mortality, but the cost-sharing environment for colonoscopies, the preferred form of screening, is complex. This paper combines a machine learning-based double-selection algorithm to perform principled covariate selection with differential exposure to the Affordable Care Act’s requirement that insurers fully cover cancer screening services as an instrumental variable to estimate the effect of cost sharing on colonoscopy utilization and price-shopping. The reduced form results show that the ACA’s requirements increased the use of colonoscopies by 1.7% and the IV results imply a price elasticity of 0.09. I do not find a price shopping response.
结直肠癌是癌症相关死亡的第二大原因,但结肠镜检查的费用分摊环境是复杂的,结肠镜检查是首选的筛查形式。本文结合了基于机器学习的双重选择算法来执行原则性的共变量选择,并对《平价医疗法案》(Affordable Care Act)的要求进行差异暴露,该法案要求保险公司完全覆盖癌症筛查服务,作为评估成本分摊对结肠镜检查使用率和价格购物的影响的工具变量。简化形式的结果表明,ACA的要求使结肠镜检查的使用增加了1.7%,IV结果意味着价格弹性为0.09。我没有发现价格购物的回应。
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引用次数: 1
Optimal M-Switch Surveillance Policies for Liver Cancer in Hepatitis C-Infected Population 丙型肝炎感染者肝癌最优m开关监测策略
Pub Date : 2017-05-10 DOI: 10.2139/ssrn.2966381
Qiushi Chen, T. Ayer, J. Chhatwal
Hepatocellular carcinoma (HCC) is the most common type of liver cancer and the fastest-growing cause of cancer-related deaths in the United States. Most HCC cases are attributed to chronic hepatitis C virus infection, which affects nearly 3 million Americans and 170 million globally. Although surveillance for HCC in hepatitis C patients can improve survival, the optimal surveillance policies remain unknown. In this study, we develop a mixed-integer programming (MIP)-based framework to systematically analyze a rich set of policies and determine the optimal HCC surveillance policies with the maximum societal net benefit. Our MIP-based framework captures two problem features that make dynamic programming-based formulation computationally intractable. In particular, our proposed framework allows to (1) explicitly formulate M-switch policies that are practical for implementation, and (2) tailor surveillance policies for each subpopulation by stratifying surveillance intervals based on the observable disease states. We theoretically analyze the HCC surveillance problem, characterize when the surveillance policies should be adapted to populations with different disease progression rates, and quantify the trade-off between decreasing HCC incidence and increasing treatment outcomes. We carefully parameterize our model using clinical trial data, a previously validated simulation model, and published clinical studies. Our numerical analyses lead to three main results with important policy implications. First, we find that, in addition to cirrhotic patients, expanding surveillance to patients in earlier stage of hepatitis C infection improves the cost-effectiveness of HCC surveillance. Second, compared with the one-size-fits-all type routine policies, we find that it is cost-effective to stratify surveillance strategies based on the stage of hepatitis C infection with less frequent cancer surveillance in earlier stages of infection. Lastly, we find that a little flexibility in the policy structure as captured by M-switch policies is sufficient to capture almost as much benefit as complex fully dynamic policies.
肝细胞癌(HCC)是最常见的肝癌类型,也是美国癌症相关死亡人数增长最快的原因。大多数HCC病例归因于慢性丙型肝炎病毒感染,该病毒影响了近300万美国人和全球1.7亿人。尽管监测丙型肝炎患者的肝细胞癌可以提高生存率,但最佳的监测政策仍然未知。在本研究中,我们开发了一个基于混合整数规划(MIP)的框架,系统地分析了一套丰富的政策,并确定了具有最大社会净效益的最佳HCC监测政策。我们基于mip的框架捕获了两个问题特征,使基于动态规划的公式在计算上难以处理。特别是,我们提出的框架允许(1)明确制定可实施的m开关政策,以及(2)根据可观察到的疾病状态对监测间隔进行分层,从而为每个亚人群量身定制监测政策。我们从理论上分析了HCC监测问题,描述了监测政策何时应适应不同疾病进展率的人群,并量化了降低HCC发病率和提高治疗结果之间的权衡。我们使用临床试验数据、先前验证的模拟模型和已发表的临床研究仔细地参数化了我们的模型。我们的数值分析得出了三个具有重要政策意义的主要结果。首先,我们发现,除了肝硬化患者外,将监测扩大到早期丙型肝炎感染患者可以提高HCC监测的成本效益。第二,与“一刀切”的常规政策相比,我们发现基于丙型肝炎感染阶段分层监测策略,在感染早期较少进行癌症监测具有成本效益。最后,我们发现M-switch策略捕获的策略结构中的一点灵活性足以获得几乎与复杂的全动态策略一样多的收益。
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引用次数: 1
The Use of Community-Based Primary Care Clinics for the Prevention of Skin Cancers: A Model Proposal 以社区为基础的初级保健诊所预防皮肤癌:一个模型建议
Pub Date : 2015-12-26 DOI: 10.2139/SSRN.3043054
Brian P. Mangum, Paul O. Dacanay, T. Mangum
Given the global, national, and local impact of skin cancer in terms of morbidity/mortality as well as direct economic cost to treat, and the fact that skin cancer development in adulthood is mediated by exposure to ultraviolet radiation in youth and adolescence, the development of a skin cancer prevention program is of primary public health importance. This program will build upon the success of a similar program developed by MD Anderson Cancer Centre, which focused on the day-care environment and which has been shown to raise the capacity of parents, caregivers and children to engage in preventative sun exposure behaviour. This prevention programme will utilize the Health Belief Model (HBM) to increase sunscreen and protective clothing usage among pre/school age children of the patients of a primary care paediatrics practice in Las Vegas, Nevada, by providing their caregivers the knowledge/capacity to recognize the risks of sun exposure and adopt healthy sun protection habits for their children.
鉴于皮肤癌在发病率/死亡率以及治疗的直接经济成本方面对全球、国家和地方的影响,以及成年期皮肤癌的发展是由青年和青春期暴露于紫外线辐射介导的事实,制定皮肤癌预防计划对公共卫生具有重要意义。该项目将以MD安德森癌症中心开发的一个类似项目的成功为基础,该项目侧重于日托环境,并已被证明可以提高父母、照顾者和儿童参与预防阳光照射行为的能力。这一预防方案将利用健康信念模型(HBM),通过向护理人员提供认识日晒风险的知识/能力,并为其子女养成健康的防晒习惯,在内华达州拉斯维加斯一家初级儿科诊所的病人的学龄前儿童中增加防晒霜和防护服的使用。
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Oncology eJournal
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