Flexible model

灵活的模型
  • 文章类型: Journal Article
    未经评估:社会经济地位对多发性硬化症患者死亡率的影响尚不清楚。目的是根据社会经济状况检查多发性硬化症的死亡率。
    UNASSIGNED:采用回顾性观察队列设计,招募来自18个法国多发性硬化症专家中心的人员参加了FrançaisdelaSclérose斑块观察。所有患者均居住在法国大都市,根据Poser或McDonald标准明确或可能诊断为多发性硬化症,并在1960年至2015年之间发病。初始表型为复发发作或原发性进行性发作。生命状态于2016年1月1日更新。社会经济地位由生态指数衡量,欧洲剥夺指数,并根据每位患者的家庭住址归因于他们。根据社会经济状况,使用带有多维惩罚样条的加性超额危险模型研究了超额死亡率。最初的假设是超额死亡率的潜在社会经济梯度。
    UNASSIGNED:共纳入34,169例多发性硬化症患者(88%复发发作(n=30,083),12%进行性发作(n=4086),复发性发作的女性/男性性别比为2.7,进行性发作为1.3)。复发发作的平均年龄为31.6(SD=9.8),进行性发作的平均年龄为42.7(SD=10.8)。在后续行动结束时,1849例患者死亡(4.4%为复发性发作(n=1311),13.2%为进行性发作(n=538))。对于复发患者发现了社会经济梯度;更贫困的患者有更高的超额死亡率。在1980年的疾病持续时间30年和症状发作一年时,被剥夺的复发发作患者(EDI=-6)和被剥夺的复发发作患者(EDI=12)之间的生存概率差异(或剥夺差距)男性为16.6%(95%置信区间(CI)[10.3%-22.9%]),女性为12.3%(95CI[7.6%-17.0%])。在进行性发作患者中未发现明确的社会经济死亡率梯度。
    UNASSIGNED:社会经济状况与复发患者多发性硬化症死亡率相关。改善更多社会经济贫困的多发性硬化症患者的整体护理可能有助于减少多发性硬化症相关死亡率的社会经济不平等。
    UNASSIGNED:本研究由ARSEP基金会资助,该基金会是“在ScléroseSclérose牌匾上的援助基金会”(授权参考编号1122)。数据收集得到了法国国家提供的赠款的支持,并由国家机构处理,在“未来投资”计划的框架内,在参考号ANR-10-COHO-002下,法国恐怖主义观察(OFSEP)。
    UNASSIGNED: The effects of socio-economic status on mortality in patients with multiple sclerosis is not well known. The objective was to examine mortality due to multiple sclerosis according to socio-economic status.
    UNASSIGNED: A retrospective observational cohort design was used with recruitment from 18 French multiple sclerosis expert centers participating in the Observatoire Français de la Sclérose en Plaques. All patients lived in metropolitan France and had a definite or probable diagnosis of multiple sclerosis according to either Poser or McDonald criteria with an onset of disease between 1960 and 2015. Initial phenotype was either relapsing-onset or primary progressive onset. Vital status was updated on January 1st 2016. Socio-economic status was measured by an ecological index, the European Deprivation Index and was attributed to each patient according to their home address. Excess death rates were studied according to socio-economic status using additive excess hazard models with multidimensional penalised splines. The initial hypothesis was a potential socio-economic gradient in excess mortality.
    UNASSIGNED: A total of 34,169 multiple sclerosis patients were included (88% relapsing onset (n = 30,083), 12% progressive onset (n = 4086)), female/male sex ratio 2.7 for relapsing-onset and 1.3 for progressive-onset). Mean age at disease onset was 31.6 (SD = 9.8) for relapsing-onset and 42.7 (SD = 10.8) for progressive-onset. At the end of follow-up, 1849 patients had died (4.4% for relapsing-onset (n = 1311) and 13.2% for progressive-onset (n = 538)). A socio-economic gradient was found for relapsing-onset patients; more deprived patients had a greater excess death rate. At thirty years of disease duration and a year of onset of symptoms of 1980, survival probability difference (or deprivation gap) between less deprived relapsing-onset patients (EDI = -6) and more deprived relapsing-onset patients (EDI = 12) was 16.6% (95% confidence interval (CI) [10.3%-22.9%]) for men and 12.3% (95%CI [7.6%-17.0%]) for women. No clear socio-economic mortality gradient was found in progressive-onset patients.
    UNASSIGNED: Socio-economic status was associated with mortality due to multiple sclerosis in relapsing-onset patients. Improvements in overall care of more socio-economically deprived patients with multiple sclerosis could help reduce these socio-economic inequalities in multiple sclerosis-related mortality.
    UNASSIGNED: This study was funded by the ARSEP foundation \"Fondation pour l\'aide à la recherche sur la Sclérose en Plaques\" (Grant Reference Number 1122). Data collection has been supported by a grant provided by the French State and handled by the \"Agence Nationale de la Recherche,\" within the framework of the \"Investments for the Future\" programme, under the reference ANR-10-COHO-002, Observatoire Français de la Sclérose en Plaques (OFSEP).
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  • 文章类型: Journal Article
    在法国,对于高度活跃的复发缓解型多发性硬化症(RRMS)患者,芬戈莫德(FNG)停药后可提供两种治疗策略:那他珠单抗(NTZ)或抗CD20.我们比较了这两种策略在OFSEP数据库中作为FNG开关的有效性。主要终点是首次复发的时间。其他结果是3个月内的复发率,是时候恶化EDSS分数了,24个月MRI恶化的患者比例,停止治疗的时间,严重不良事件的发生率。使用多维惩罚样条对事件速率随时间的动态进行建模,允许以灵活的方式对协变量的影响进行建模的可能性,考虑非线性和相互作用。总共包括740名患者(337名在抗CD20下和403名在NTZ下)。关于首次复发的动态,两种治疗方法之间没有差异,开始时的每月概率为5.0%,6个月后为1.0%。两组的EDSS恶化率增加至6个月,然后下降。在24个月时没有观察到新的T2病变的患者比例的差异。经过18个月的随访,与抗CD20相比,NTZ停药的风险更大.这项研究显示,在FNG转换后,NTZ和抗CD20之间的临床和放射学活性没有差异。这些治疗的效果在6个月后是最佳的,并且在18个月后停药NTZ更频繁。可能主要与JC病毒血清转化有关。
    In France, two therapeutic strategies can be offered after fingolimod (FNG) withdrawal to highly active relapsing-remitting multiple sclerosis (RRMS) patients: natalizumab (NTZ) or anti-CD20. We compared the effectiveness of these two strategies as a switch for FNG within the OFSEP database. The primary endpoint was the time to first relapse. Other outcomes were the relapse rates over 3-month periods, time to worsening the EDSS score, proportion of patients with worsened 24-month MRI, time to treatment discontinuation, and incidence rates of serious adverse events. The dynamics of event rates over time were modeled using multidimensional penalized splines, allowing the possibility to model the effects of covariates in a flexible way, considering non-linearity and interactions. A total of 740 patients were included (337 under anti-CD20 and 403 under NTZ). There was no difference between the two treatments regarding the dynamic of the first occurrence of relapse, with a monthly probability of 5.0% at initiation and 1.0% after 6 months. The rate of EDSS worsening increased in both groups until 6 months and then decreased. No difference in the proportion of patients with new T2 lesions at 24 months was observed. After 18 months of follow-up, a greater risk of NTZ discontinuation was found compared to anti-CD20. This study showed no difference between NTZ and anti-CD20 after the FNG switch regarding the clinical and radiological activity. The effect of these treatments was optimal after 6 months and there was more frequent discontinuation of NTZ after 18 months, probably mainly related to JC virus seroconversions.
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  • 文章类型: Journal Article
    With improvements in acute myeloid leukemia (AML) diagnosis and treatment, more patients are surviving for longer periods. A French population of 9453 AML patients aged ≥15 years diagnosed from 1995 to 2015 was studied to quantify the proportion cured (P), time to cure (TTC) and median survival of patients who are not cured (MedS). Net survival (NS) was estimated using a flexible model adjusted for age and sex in sixteen AML subtypes. When cure assumption was acceptable, the flexible cure model was used to estimate P, TTC and MedS for the uncured patients. The 5-year NS varied from 68% to 9% in men and from 77% to 11% in women in acute promyelocytic leukemia (AML-APL) and in therapy-related AML (t-AML), respectively. Major age-differenced survival was observed for patients with a diagnosis of AML with recurrent cytogenetic abnormalities. A poorer survival in younger patients was found in t-AML and AML with minimal differentiation. An atypical survival profile was found for acute myelomonocytic leukemia and AML without maturation in both sexes and for AML not otherwise specified (only for men) according to age, with a better prognosis for middle-aged compared to younger patients. Sex disparity regarding survival was observed in younger patients with t-AML diagnosed at 25 years of age (+28% at 5 years in men compared to women) and in AML with minimal differentiation (+23% at 5 years in women compared to men). All AML subtypes included an age group for which the assumption of cure was acceptable, although P varied from 90% in younger women with AML-APL to 3% in older men with acute monoblastic and monocytic leukemia. Increased P was associated with shorter TTC. A sizeable proportion of AML patients do not achieve cure, and MedS for these did not exceed 23 months. We identify AML subsets where cure assumption is negative, thus pointing to priority areas for future research efforts.
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  • 文章类型: Journal Article
    BACKGROUND: In recent years, a variety of clinical decision-support systems (CDSS) have been developed to monitor the health of patients with chronic disease from far away. These systems are effective in overcoming human resource limitation and analyzing information generated by Tele-monitoring systems. These systems, however, are limited to monitoring a particular disease, which allows them to be used only in one specific disease. In reuses of these systems to monitor other diseases, we need to re-establish a new system with a new knowledge base. However, this type of healthcare system faces many challenges, including low scalability for change, so that, if we want to modify a health monitoring system designed for a specific disease to be used for another disease, these changes will be very substantial, meaning that, most components of that system should be changed. The lack of scalability in these systems has led to the creation of multiple health monitoring systems, while many of these systems share a common structure.
    OBJECTIVE: In this paper, to solve the scalability problem, architecture has been presented that allows a set of CDSSs to be placed on a common platform for Tele-monitoring.
    METHODS: In order to provide the proposed architecture in this study, we extracted the related concepts from the literature. The anatomical concepts used in these studies are as follow: users, transmitted data, patient data storage databases, data transfer network, and medical setting and the work is done in this setting. Finally, to design the proposed architecture, UML has been used.
    RESULTS: The innovation of this research is to provide a scalable and flexible architecture, which as a platform, is able to monitor multiple diseases with a common infrastructure. In this architecture, all components are commonly used simultaneously without the interference of several CDSSs.
    CONCLUSIONS: Utilizing the proposed model in this paper, while reducing the setup costs and speeding up the launch of various remote monitoring systems, many rework in the implementation of these systems is also reduced.
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  • 文章类型: Journal Article
    基于汇总数据估计非线性剂量反应曲线的标准两阶段方法通常排除那些少于三个暴露组的研究。我们将一阶段方法开发为线性混合模型,并介绍了该方法的主要方面,包括型号规格,估计,测试,预测,拟合优度,模型比较,以及研究间异质性的量化。使用已发布的荟萃分析中的虚构和真实数据,我们说明了所提出的方法的主要特点,并将其与传统的两阶段分析进行了比较。在一个阶段的方法中,研究间异质性的合并曲线和估计值基于整套研究,没有任何排除.因此,甚至复杂的曲线(样条,可以估计由几个参数定义的零曝光处的尖峰)。我们展示了一阶段方法如何促进几个应用程序,特别是对暴露范围内的异质性的量化,边际曲线和条件曲线的预测,以及替代模型的比较。非线性曲线荟萃分析的一阶段方法在dosresmetaR包中实现。它特别适合于聚合的剂量反应荟萃分析,其中通过包括所有研究来更好地解决研究问题的复杂性。
    The standard two-stage approach for estimating non-linear dose-response curves based on aggregated data typically excludes those studies with less than three exposure groups. We develop the one-stage method as a linear mixed model and present the main aspects of the methodology, including model specification, estimation, testing, prediction, goodness-of-fit, model comparison, and quantification of between-studies heterogeneity. Using both fictitious and real data from a published meta-analysis, we illustrated the main features of the proposed methodology and compared it to a traditional two-stage analysis. In a one-stage approach, the pooled curve and estimates of the between-studies heterogeneity are based on the whole set of studies without any exclusion. Thus, even complex curves (splines, spike at zero exposure) defined by several parameters can be estimated. We showed how the one-stage method may facilitate several applications, in particular quantification of heterogeneity over the exposure range, prediction of marginal and conditional curves, and comparison of alternative models. The one-stage method for meta-analysis of non-linear curves is implemented in the dosresmeta R package. It is particularly suited for dose-response meta-analyses of aggregated where the complexity of the research question is better addressed by including all the studies.
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