Mortality modeling of early detection programs

Summary .   Consider a group of subjects who are offered an opportunity to receive a sequence of periodic special examinations for the purpose of diagnosing a chronic disease earlier relative to usual care. The mortality for the early detection group is to be compared with a group receiving usual care. Benefit is reflected in a potential reduction in mortality. This article develops a general probability model that can be used to predict cumulative mortality for each of these groups. The elements of the model assume (i) a four-state progressive disease model in which a subject may be in a disease-free state (or a disease state that cannot be detected), preclinical disease state (capable of being diagnosed by a special exam), clinical state (diagnosis by usual care), and a death state; (ii) age-dependent transitions into the states; (iii) age-dependent examination sensitivity; (iv) age-dependent sojourn time in each state; and (v) the distribution of disease stages on diagnosis conditional on modality of detection. The model may be used to (i) compare mortality rates for different screening schedules; (ii) explore potential benefit of subpopulations; and (iii) compare relative reductions in disease-specific mortality due to advances and dissemination of both treatment and early detection screening programs.     

Simple parametric and nonparametric models for excess and relative mortality

This paper studies two classes of hazard-rate-based models for the mortality in a group of individuals taking normal life expectancy into account. In a multiplicative hazard model, the estimate for the relative mortality generalises the standardised mortality ratio, and the adequacy of a model with constant relative mortality can be tested using a type of total time on test statistic. In an additive hazard model, continuous-time generalisations of a "corrected" survival curve and a "normal" survival curve are obtained, and the adequacy of a model with constant excess mortality can again be tested using a type of total time on test statistic. A model including both the multiplicative hazard model and the additive hazard model is briefly considered. The use of the models is illustrated on a set of data concerning survival after operation for malignant melanoma.     

改良半椎板切除法建立大鼠腰神经根压迫模型

目的探讨改良半椎板切除法建立大鼠腰神经根压迫模型的优势和特点。方法选用SD大鼠40只,随机分为实验组和对照组,实验组采用改良半椎板切除法建立大鼠腰神经根压迫模型,对照组则采用全椎板切除法,通过观察两组建模手术时间、术中出血量、伤口愈合情况、死亡率、大鼠下肢神经功能、神经根组织病理改变及TNF-α及IL-1在细胞质中灰度值表达水平评估两种方法的效果。结果实验组在建模手术时间、术中出血量、伤口愈合状况、死亡率明显少于对照组(P0.01),而大鼠下肢神经功能、神经根组织病理改变及TNF-α及IL-1在细胞质中灰度值表达水平无明显差异,同时,实验组所需的切口小,脊柱后方软组织破坏少。结论采用改良半椎板切除法可保证成功建立大鼠腰神经根压迫模型,并且这一改良方法具有手术时间短,伤口愈合快,出血量少,软组织破坏少,死亡率低等优点,这一改良方法更注重动物伦理。     

Bayesian extrapolation of space-time trends in cancer registry data

We apply a full Bayesian model framework to a dataset on stomach cancer mortality in West Germany. The data are stratified by age group, year, and district. Using an age-period-cohort model with an additional spatial component, our goal is to investigate whether there is evidence for space-time interactions in these data. Furthermore, we will determine whether a period-space or a cohort-space interaction model is more appropriate to predict future mortality rates. The setup will be fully Bayesian based on a series of Gaussian Markov random field priors for each of the components. Statistical inference is based on efficient algorithms to block update Gaussian Markov random fields, which have recently been proposed in the literature.     

基于终末期肝病评分模型对91例乙型肝炎病毒相关性慢加急肝衰竭患者预后的评估及死亡危险因素分析

采用9种终末期肝病预后评分模型对乙型肝炎病毒相关性慢加急肝衰竭(hepatitis B virus-related acute-on-chronic liver failure,HBV-ACLF)患者进行预后评估,分析引起HBV-ACLF患者死亡的危险因素。连续收集2014年7月—2018年7月复旦大学附属华山医院确诊的HBV-ACLF患者,通过评估受试者工作特征曲线的曲线下面积(area under receiver operating characteristic curve,AUROC),判断目前9种终末期肝病预后评分模型预测HBV-ACLF患者预后的准确性。采用多因素Logistic回归分析,探讨HBV-ACLF患者死亡的危险因素。共纳入91例HBV-ACLF患者,死亡46例。COSSH-ACLFs评分对轻度、重度患者的短期和中期预后具有最佳预测能力(总体死亡率AUROC:28d为0.946,90d为0.920;按器官衰竭数量分级,0～1级:28d为0.900,90d为0.846;2～3级:28d为0.957,90d为0.917);确定COSSH-ACLFs评分的最佳临界点为6.245,生存曲线分析显示评分>6.245的患者生存率明显低于评分≤6.245的患者(10.7%vs.81.8%,P<0.000 1)。年龄、总胆红素、血小板计数、凝血系统衰竭、肝性脑病是HBV-ACLF患者死亡的独立危险因素。死亡组患者血小板计数显著低于生存组(P<0.002 2),血小板计数≤63×10~9/L与HBVACLF患者病情严重程度及预后显著相关。本研究证实COSSH-ACLFs评分模型预测HBV-ACLF患者预后的能力较其他评分模型更为准确,血小板计数与HBV-ACLF患者病情严重程度及预后显著相关。     

水合氯醛、乌拉坦及其1：1混合液在SD大鼠麻醉中的效果比较及应用

目的：比较水合氯醛、乌拉坦及其1：1混合液在SD大鼠麻醉中的效果并进一步在大鼠模型制备的麻醉中检验其效果。方法：分别采用不同剂量的水合氯醛和乌拉坦及其1：1混合液进行麻醉实验,比较其麻醉起效时间、维持时间和死亡率,并将相同剂量的1：1混合液应用于SD大鼠模型制作时的麻醉中,比较其与非模型组之间的差异。结果：水合氯醛和乌拉坦混合液麻醉大鼠的起效时间2.5±1.5分钟,与单用水合氯醛无差异（P〉0.05）,比单用乌拉坦起效时间短（P〈0.05）;维持时间107.4±4.1分钟,比单用水合氯醛、乌拉坦长（P〈0.01）;麻醉死亡率比单用水合氯醛低,总死亡率比单用水合氯醛、乌拉坦低。模型组大鼠的麻醉起效时间2.9±1.6分钟,维持时间108.9±4.4分钟,零麻醉死亡率,总死亡率为2.5%;与1：1混合液非模型组的麻醉效果没有明显差异。结论：水合氯醛＋乌拉坦1：1混合液麻醉效果好、起效快、死亡率极低,适合用于2小时左右的SD大鼠手术或模型制作。     

水合氯醛、乌拉坦及其1:1 混合液在SD 大鼠麻醉中的效果比较及应用

目的:比较水合氯醛、乌拉坦及其1:1混合液在SD大鼠麻醉中的效果并进一步在大鼠模型制备的麻醉中检验其效果。方法:分别采用不同剂量的水合氯醛和乌拉坦及其1:1混合液进行麻醉实验,比较其麻醉起效时间、维持时间和死亡率,并将相同剂量的1:1混合液应用于SD大鼠模型制作时的麻醉中,比较其与非模型组之间的差异。结果:水合氯醛和乌拉坦混合液麻醉大鼠的起效时间2.5±1.5分钟,与单用水合氯醛无差异(P>0.05),比单用乌拉坦起效时间短(P<0.05);维持时间107.4±4.1分钟,比单用水合氯醛、乌拉坦长(P<0.01);麻醉死亡率比单用水合氯醛低,总死亡率比单用水合氯醛、乌拉坦低。模型组大鼠的麻醉起效时间2.9±1.6分钟,维持时间108.9±4.4分钟,零麻醉死亡率,总死亡率为2.5%;与1:1混合液非模型组的麻醉效果没有明显差异。结论:水合氯醛+乌拉坦1:1混合液麻醉效果好、起效快、死亡率极低,适合用于2小时左右的SD大鼠手术或模型制作。     

心脏手术风险评估欧洲系统在OPCAB术后ICU中的应用

现在对于不停跳冠脉旁路移植术(OPCAB)的患者术后的预测的模型有很多种,这些模型大多用于预测术后死亡率、术后并发症,手术方式的选择、手术资源的应用价值的评估等。心脏手术风险评估欧洲系统(Euro SCORE)也是其中一种,它对于现代OPCAB术后死亡率的预测比较合理。但是随着手术外科的发展,Euro SCORE模型在中、低危组过高估计术后的死亡率,而在高危组又过低估计术后死亡率。此外,Euro SCORE模型也应用于预测术后并发症、住院费用多少、在ICU住院时间及机械通气时间,得到广泛应用,并在世界范围内得到推广,包括欧美等国家。最近在中国,也开始对心脏手术风险评估欧洲系统大量了的数据研究,并发展到对其他手术术后的预测及治疗。     

链脲佐菌素诱导SD和Wistar大鼠糖尿病模型的影响因素

目的通过注射链脲佐菌素（STZ）制作SD和Wistar大鼠糖尿病模型,观察大鼠品系、给药剂量、给药次数对大鼠成模率、死亡率的影响,同时研究利用口服葡萄糖耐量试验（OGTT）判断大鼠糖尿病成模率的意义。方法设置共同的正常对照组,①Wistar大鼠随机分为中剂量组（55 mg/kg）和高剂量组（65 mg/kg）;②SD大鼠一次性腹腔注射STZ（55 mg/kg）,与①中的Wistar大鼠作对比;③SD大鼠随机分为一次给药组和两次给药组,注射剂量均为55 mg/kg,观察期间进行OGTT。结果①Wistar大鼠成模率和死亡率均高于SD大鼠;②采用SD大鼠、中剂量给药和两次给药的方式可提高成模率,并降低死亡率;③在有明确胰岛病理改变的模型组大鼠,其OGTT异常阳性率显著高于空腹血糖异常阳性率。结论用STZ诱导糖尿病模型是一种稳定可靠的方法。Wistar大鼠成模率和死亡率均高于SD大鼠;选用中剂量给药及两次给药的方式可提高SD大鼠成模率,并降低死亡率,维持时间较长。在动物实验中OGTT比空腹血糖监测更有诊断意义,不易造成漏诊。     

Differential mortality in Turkana agriculturalists and pastoralists

Nomadic pastoral populations appear to have much lower rates of growth than the otherwise very high growth rates now characteristic of populations in developing nations. Because dramatic declines in infant mortality have been a primary contributor to increased population growth rates in these countries, it has been assumed that nomadic pastoral populations are still characterized by high levels of mortality in the first few years of life. Few studies, however, have been undertaken to estimate demographic parameters for nomadic pastoral populations, and even fewer of a comparative nature have been undertaken to document the impact of subsistence strategy on demographic processes. This study compares indirect childhood mortality estimates for Turkana nomadic pastoralists with childhood mortality in a settled agricultural group within the same population and finds that pastoralists have substantially higher levels of mortality. Based on the childhood mortality estimates, model life tables are selected for pastoral and agricultural groups from which values for mean life expectancy and infant mortality are estimated and compared. Recent improvements in primary health care for the settled agricultural group are ruled out as being an important cause of their lower mortality levels, and some aspects of life-style associated with subsistence strategy are discussed as likely determinants of the mortality differences.     

Decreased mortality in a rat model of acute postinfarction heart failure

INTRODUCTION: The rat model of postinfarction heart failure (HF) has been very valuable in experimental cardiology. One disadvantage of this model is the very high acute mortality (70-80%). The aim of this study was to evaluate whether measures of intensive cardiac care applied to rats with acute myocardial infarction (MI) would reduce mortality. METHODS: Male Sprague-Dawley rats weighing approximately 300 g were used. The animals were randomized into two groups. The intensive care group (IC) n=20 and conventional care group (CC) n=20. Experimental MI was induced by ligation of the left coronary artery producing large anterolateral MI. Animals in the IC group received isoflurane anesthesia and respiratory support postoperatively. The heart rhythm was monitored continuously and ventricular arrhythmias were treated with amiodarone and cardioversion. RESULTS: Mortality rate within 24 h was 4/20 (20%) in the IC group and 14/20 (70%) in the CC group (p<0.01). This represents a 3.5-fold reduction in acute mortality rate. CONCLUSIONS: The use of amiodarone, respiratory support, isoflurane gas anesthesia, and electrical cardioversion of malignant arrhythmias are simple and effective measures to reduce mortality in rats with acute MI and HF. Improving survival rates increases cost-efficiency and ethical acceptance of this important experimental HF model.     

Anti-TNF antibody treatment reduces mortality in experimental dengue virus infection

Here we describe a lethal mouse model infected with dengue virus type 2 with several similarities to human DEN-2 infection. Clinically animals demonstrated anemia, thrombocytopenia, pre-terminal paralysis and shock. The most impressive changes were seen with tumor necrosis factor (TNF)-alpha, which abruptly and steeply increased 24 h before the exitus (mean at day 6). Serum levels of IL-1beta, IL-6, IL-10, IL-1 receptor antagonist and soluble TNF receptor I continuously increased during the time of infection. A 100% mortality rate was noted in that group of animals. Treating animals with anti-TNF-alpha serum reduced mortality rate down to 40% (P<0.05). Our model supports the view that activation of innate immune response is at least partially responsible for mortality in DEN-2 infection, and in line with this concept, anti-TNF treatment significantly reduces mortality rates.     

改良线栓法大鼠大脑中动脉阻塞模型的建立

目的对大鼠大脑中动脉阻塞（MCAO）再灌注模型进行改良,通过比较再灌注24h时大鼠神经功能评分、梗死率、模型制作时间、成功率和死亡率等指标评价改良线栓法大鼠MCAO再灌注模型的有效性。方法12只SD大鼠随机分为对照和模型两组,对照组采用分离结扎翼腭动脉,从颈外动脉插入线栓至大脑中动脉。模型组采用不分离结扎翼腭动脉,从颈总动脉分叉处插入线栓至大脑中动脉。阻断大脑中动脉血供2h后将线栓拔出实现再灌注。于再灌注24h时观察脑组织组织病理学改变,计算比较两组大鼠神经功能评分、模型制作时间、模型成功率和死亡率以及鼠脑切片TTC染色测量脑梗死率。结果两组MCAO模型在再灌注24h后大鼠神经功能评分、梗死率、模型成功率和死亡率等方面没有显著差异;模型组的模型制作时间显著少于对照组（P〈0．05）。结论采用不分离结扎翼腭动脉,由颈总动脉插入线栓的改良线栓法是稳定和可靠的MCAO造模方法。     

Model life table for captive chimpanzees

Mortality statistics from three captive populations of chimpanzees (Pan troglodytes) were combined to generate standard model life tables for each sex in this species. The model is compared to an estimate of survivorship of a group of wild animals, and is applied to an incomplete data set to illustrate how the model may be used to extend estimates of mortality statistics to missing older ages. © 1995 Wiley-Liss, Inc.     

Estimating and modeling the cure fraction in population-based cancer survival analysis

In population-based cancer studies, cure is said to occur when the mortality (hazard) rate in the diseased group of individuals returns to the same level as that expected in the general population. The cure fraction (the proportion of patients cured of disease) is of interest to patients and is a useful measure to monitor trends in survival of curable disease. There are 2 main types of cure fraction model, the mixture cure fraction model and the non-mixture cure fraction model, with most previous work concentrating on the mixture cure fraction model. In this paper, we extend the parametric non-mixture cure fraction model to incorporate background mortality, thus providing estimates of the cure fraction in population-based cancer studies. We compare the estimates of relative survival and the cure fraction between the 2 types of model and also investigate the importance of modeling the ancillary parameters in the selected parametric distribution for both types of model.     

The Influential Roles of Antibiotics Prophylaxis in Cirrhotic Patients with Peptic Ulcer Bleeding after Initial Endoscopic Treatments

The influential roles of antibiotic prophylaxis on cirrhotic patients with peptic ulcer bleeding are still not well documented. The purpose of this study is to clarify these influential roles and to identify the risk factors associated with rebleeding, bacterial infection and in-hospital mortality. A cross-sectional, chart review study was conducted on 210 cirrhotic patients with acute peptic ulcer hemorrhage who underwent therapeutic endoscopic procedures. Patients were divided into group A (with prophylactic intravenous ceftriaxone, n = 74) and group B (without antibiotics, n = 136). The outcomes were length of hospital days, prevention of infection, rebleeding rate and in-hospital mortality. Our results showed that more patients suffered from rebleeding and infection in group B than group A (31.6% vs. 5.4%; p<0.001 and 25% vs. 10.8%; p = 0.014 respectively). The risk factors for rebleeding were active alcoholism, unit of blood transfusion, Rockall score, model for end-stage liver disease score and antibiotic prophylaxis. The risk factors for infection were active alcoholism, Child-Pugh C, Rockall score and antibiotic prophylaxis. Rockall score was the predictive factor for in-hospital mortality. In conclusions, antibiotic prophylaxis in cirrhotic patients after endoscopic interventions for acute peptic ulcer hemorrhage reduced infections and rebleeding rate but not in-hospital mortality. Rockall score was the predictive factor of in-hospital mortality.     

Proteinuria: value as predictor of cardiovascular mortality in insulin dependent diabetes mellitus.

The relation between diabetic microangiopathy and macroangiopathy was studied by analysing the relative mortality from cardiovascular disease in patients with insulin dependent diabetes mellitus with and without persistent proteinuria. The study group comprised 2890 diabetics diagnosed between 1933 and 1972 before the age of 31, and the study was conducted by using the linear logistic discrete failure time model. In patients with proteinuria the relative mortality from cardiovascular disease was 37 times that in the general population; in patients without proteinuria it was 4.2 times that in the general population. In both groups women had a relative mortality twice to 2.6 times that of men. In neither group was relative mortality correlated with duration of diabetes, suggesting that the association between diabetes and cardiovascular disease may be conferred by factors other than hyperglycaemia and hyperinsulinaemia. The high relative mortality from cardiovascular disease in diabetics with proteinuria indicates a strong association between diabetic microangiopathy and macroangiopathy, suggesting a common (pathogenetic?) mechanism for these two late diabetic complications.     

Population dynamics of obligate cooperators

Obligate cooperative breeding species demonstrate a high rate of group extinction, which may be due to the existence of a critical number of helpers below which the group cannot subsist. Through a simple model, we study the population dynamics of obligate cooperative breeding species, taking into account the existence of a lower threshold below which the instantaneous growth rate becomes negative. The model successively incorporates (i) a distinction between species that need helpers for reproduction, survival or both, (ii) the existence of a migration rate accounting for dispersal, and (iii) stochastic mortality to simulate the effects of random catastrophic events. Our results suggest that the need for a minimum number of helpers increases the risk of extinction for obligate cooperative breeding species. The constraint imposed by this threshold is higher when helpers are needed for reproduction only or for both reproduction and survival. By driving them below this lower threshold, stochastic mortality of lower amplitude and/or lower frequency than for non-cooperative breeders may be sufficient to cause the extinction of obligate cooperative breeding groups. Migration may have a buffering effect only for groups where immigration is higher than emigration; otherwise (when immigrants from nearby groups are not available) it lowers the difference between actual group size and critical threshold, thereby constituting a higher constraint.     

Surgical porcine myocardial infarction model through permanent coronary occlusion

Using domestic pigs as an animal model, we here validated a reproducible and standardized myocardial infarction (MI) surgical model, to achieve the largest possible infarct extent with the lowest morbidity and mortality. To this end, we included several anesthetic and perisurgical precautions to minimize surgical complications. Mortality and morbidity rates were compared among groups of pigs that underwent permanent occlusion at different locations of either the left circumflex or left anterior descending artery. In addition, to compare the resulting MI between groups, data were collected by using cardiac biomarkers (including troponin I), electrocardiography, and echocardiography. These data were correlated to the final mean infarct size calculated by microscopic studies. Proximal occlusions lead to high mortality rates, whereas distal occlusions induced rather small MI areas. The optimal occlusion site in terms of morbidity, mortality, and lesion extent was the midpoint of the left anterior descending artery. In this group, only one pig died, and group cardiac data showed a rise in biomarker levels, marked left ventricular dysfunction on electrocardiography and echocardiography, and well-defined transmural MI in both ventricles. Infarct size quantitated through histologic studies revealed an average 15% ventricular lesion. Because interanimal variability in results from this group was negligible, we consider that the induced myocardial injury of this model is reliable.     

Increasing pre-term and low-birth-weight rates over time and their impact on infant mortality in south-east Brazil

This study investigates the possible effects of pre-term births and low birth weight on infant mortality rates (IMRs) over a 15-year period in Ribeir?o Preto, Brazil, based on surveys carried out in 1978/79 and 1994. The 1978/79 survey included 6750 births over a 12-month period and the 1994 survey 2846 births over a 4-month period. Infant deaths were retrieved monthly from the city register. Infant mortality rate decreased from 36.6 to 16.9 deaths per 1000 over 15 years. The decrease in IMR was larger in the 2500-2999 g group than in any other group. The observed falls in IMR were attributable to decreases in birth-weight-specific mortality rates. Likewise, there was a general decrease in IMR in mild, moderate and severe pre-term births. The incidence rate ratio of infant mortality between surveys was 0.46 (95% CI 0.34-0.63); it increased to 0.57 (95% CI 0.35-0.75) when adjusted for birth weight and other factors in the model and rose to 0.69 (95% CI 0.49-0.97) when adjusted for length of gestation and other variables. The increase in pre-term births and low birth weight may have had, at most, a marginal effect on the IMR. Progress in the care of newborns may have decreased the mortality risk, but even mild pre-term birth still has an impact on infant mortality. There is room for further improvement in IMR by tackling the high rates of pre-term birth.