The XGTDL family of survival distributions

AbstractNon-PH parametric survival modelling is developed within the framework of the multiple logistic function. The family considered comprises three basic models: (a) a PH model, (b) an accelerated life model and (c) a model which is non-proportional hazards and non-accelerated life. The last model, the generalised time-dependent logistic model was described first by the author in 1996 and this model gives its name to the entire family. The family is generalised by means of a Gamma frailty extension which is shown to accommodate crossing hazards data. A further generalisation is the inclusion of a dispersion model. These extensions lead naturally to the concept of a multi-parameter regression model described by Burke and MacKenzie in which the scale and shape parameters are modelled simultaneously as functions of covariates. Where possible, we include the MPR extension in the XGTDL family. Following a simulation study, the new models are used to analyse two sets survival data and the methods are discussed.

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A Brief Overview of Restricted Mean Survival Time Estimators and Associated Variances

Stats ◽

10.3390/stats3020010 ◽

2020 ◽

Vol 3 (2) ◽

pp. 107-119 ◽

Cited By ~ 1

Author(s):

Szilárd Nemes ◽

Erik Bülow ◽

Andreas Gustavsson

Keyword(s):

Survival Time ◽

Survival Data ◽

Proportional Hazards ◽

Survival Times ◽

Mean Survival Time ◽

Model Free ◽

Kaplan Meier ◽

Restricted Mean Survival Time ◽

Parametric Survival ◽

Method Analysis

Restricted Mean Survival Time ( R M S T ) experiences a renaissance and is advocated as a model-free, easy to interpret alternative to proportional hazards regression and hazard rates with implication in causal inference. Estimation of R M S T and associated variance is mainly done by numerical integration of Kaplan–Meier curves. In this paper we briefly review the two main alternatives to the Kaplan–Meier method; analysis based on pseudo-observations, and the flexible parametric survival method. Using computer simulations, we assess the efficacy of the three methods compared to a fully parametric approach where the distribution of survival times is known. Thereafter, the three methods are directly compared without any distributional assumption for the survival data. Generally, flexible parametric survival methods outperform both competitors, however the differences are small.

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Multi-state network meta-analysis of cause-specific survival data

10.1101/2020.11.13.20231332 ◽

2020 ◽

Author(s):

Jeroen P. Jansen ◽

Devin Incerti ◽

Thomas Trikalinos

Keyword(s):

Survival Data ◽

Treatment Effects ◽

Proportional Hazards ◽

Treatment Effectiveness ◽

Meta Analysis ◽

Progression Free Survival ◽

Evidence Base ◽

Free Survival ◽

Parametric Survival ◽

Cause Specific Survival

AbstractMultiple randomized controlled trials, each comparing a subset of competing interventions, can be synthesized by means of a network meta-analysis to estimate relative treatment effects between all interventions in the evidence base. Often there is an interest in estimating the relative treatment effects regarding time-to-event outcomes. Cancer treatment effectiveness is frequently quantified by analyzing overall survival (OS) and progression-free survival (PFS). In this paper we introduce a method for the joint network meta-analysis of PFS and OS that is based on a time-inhomogeneous tri-state (stable, progression, and death) Markov model where time-varying transition rates and relative treatment effects are modeled with known parametric survival functions or fractional polynomials. The data needed to run these analyses can be extracted directly from published survival curves. We demonstrate use by applying the methodology to a network of trials for the treatment of non-small-cell lung cancer. The proposed approach allows the joint synthesis of OS and PFS, relaxes the proportional hazards assumption, extends to a network of more than two treatments, and simplifies the parameterization of decision and cost-effectiveness analyses.

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Social and Familial Factors in the Development of Early Childhood Asthma

PEDIATRICS ◽

10.1542/peds.75.5.859 ◽

1985 ◽

Vol 75 (5) ◽

pp. 859-868 ◽

Cited By ~ 1

Author(s):

L. J. Horwood ◽

D. M. Fergusson ◽

F. T. Shannon

Keyword(s):

Early Childhood ◽

Birth Cohort ◽

Childhood Asthma ◽

Proportional Hazards ◽

Large Range ◽

Significant Risk ◽

Social Background ◽

Familial Factors ◽

The Family

The role of social and familial factors in the development of childhood asthma by age 6 years was studied in a birth cohort of New Zealand children. Rates of asthma varied markedly with the child's sex; boys had twice the rate of asthma as girls. In addition, the factors associated with asthma varied with the child's sex. For boys, wheeze during infancy, early eczema, and parental asthma were all significant risk factors; for girls, the only risk factor was early eczema. Proportional hazards modeling of the data failed to show any significant associations between the development of asthma and a large range of other social and familial factors including breast-feeding, parental smoking habits, pets in the child's family, stress in the family, or family social background. It was concluded that asthma in early childhood appeared to be inherited to some extent, its age of expression was related to the child's sex, and it had a complex interaction with other forms of allergic disease. There was no evidence to suggest that the structure, practices, or dynamics of the child's family played a significant role in the development of asthma for children in this birth cohort.

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IMPACT OF CYSTIC FIBROSIS ON FAMILY FUNCTIONING

PEDIATRICS ◽

10.1542/peds.34.1.67 ◽

1964 ◽

Vol 34 (1) ◽

pp. 67-71

Author(s):

Juanita Turk

Keyword(s):

Cystic Fibrosis ◽

Family Relationships ◽

Psychological Functioning ◽

Sick Child ◽

The Other ◽

Family Needs ◽

Entire Family ◽

The Social ◽

The Family ◽

Family Service Agencies

This study was undertaken to determine whether families of children with cystic fibrosis were experiencing difficulties in meeting family needs and in maintaining normal family relationships. It was found that families were not deprived of the essentials of living, but they were not able to maintain their usual pattern of family relationships. Time and energy precluded carrying on activities with each other and with the children; and there was breakdown in their ability to communicate adequately between themselves and the children regarding important family issues. In order to preserve the family as a functioning unit, someone has to be concerned about the entire family. Of necessity, the family has focused on the sick child, leaving the physician, the nurse, the social worker and/or the social agencies to help the family refocus on its total situation, rather than just a part of it. Traditionally, the mother takes care of the sick child. It is she who takes the child to the doctor's office and is responsible for carrying out his recommendations. In the care of a CF child, she assumes a heavy burden and frequently is fatigued from this responsibility. Because she is so tired and so occupied, she may misunderstand or distort what she is told by the physician, and may not be able to tell her husband or the children what they need to know in order to participate in family activities and in the care of the CF child. This situation can easily lead to misunderstanding and tension within the family. To avoid this, both parents could be encouraged, at some point, to come together to the physician's office for discussion. Such discussions could lead to more consideration and appreciation being given to each other. It might lessen the tendency for each to blame the other for the child's illness and could avoid the feeling voiced by one mother, "I would like to blow him out of his chair so that he would help me and understand what I go through." We also need to realize that the CF child is frequently aware of the demands he makes on the family. If these demands are not discussed freely, then everyone is caught in a "web of silence" revolving around his own feelings of frustration. This creates a burden for everyone, including the CF child, and if not discussed it can impair the psychological functioning of all members. The CF child needs to be encouraged to participate in his own care program and to assume some responsibilities for himself. He should not reach the age of seven being unable to tie his own shoes or dress himself, as has been observed in some CF children. It would seem feasible, therefore, that the CF child should have an awareness of what is wrong with him, and what his abilities and limitations are. The other siblings should also be given as much explanation as possible because they, too, are part of the family and attention and care is being diverted from them. This explanation could make for more understanding on the sibling's part. While it would still be difficult for him to accept some of the decisions made (such as why the parents could not get home from the hospital in order for him to use the family car for a senior prom), he would know that it was the situation that was causing the decrease in attention and care rather than rejection of him by the parents. In order to give these families as much assistance as possible, the community's resources should be utilized. Frequently, the parents are unaware of these or need encouragement to avail themselves of services. The homemaker service or visiting nurse service could free the family from constant care; the local youth program could be helpful to the siblings in the family, and Family Service Agencies could be used for counseling on family problems. In summary, this study points up the need for the total family to have an understanding and awareness of CF and to share such knowledge with one another; that all problems of the family have to be considered and not just those of the CF child; and that help from other professional people should be utilized along with sources of the community.

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1388. Dose Discrimination for ASN100: Bridging from Rabbit Survival Data to Predicted Activity in Humans Using a Minimal Physiologically Based Pharmacokinetic (mPBPK) Model

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.1219 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S426-S426

Author(s):

Christopher M Rubino ◽

Lukas Stulik ◽

Harald Rouha ◽

Zehra Visram ◽

Adriana Badarau ◽

...

Keyword(s):

Survival Data ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Model ◽

Virulent Strain ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Simulated Patients ◽

Research Support ◽

Mpbpk Model

Abstract Background ASN100 is a combination of two co-administered fully human monoclonal antibodies (mAbs), ASN-1 and ASN-2, that together neutralize the six cytotoxins critical to S. aureus pneumonia pathogenesis. ASN100 is in development for prevention of S. aureus pneumonia in mechanically ventilated patients. A pharmacometric approach to dose discrimination in humans was taken in order to bridge from dose-ranging, survival studies in rabbits to anticipated human exposures using a mPBPK model derived from data from rabbits (infected and noninfected) and noninfected humans [IDWeek 2017, Poster 1849]. Survival in rabbits was assumed to be indicative of a protective effect through ASN100 neutralization of S. aureus toxins. Methods Data from studies in rabbits (placebo through 20 mg/kg single doses of ASN100, four strains representing MRSA and MSSA isolates with different toxin profiles) were pooled with data from a PK and efficacy study in infected rabbits (placebo and 40 mg/kg ASN100) [IDWeek 2017, Poster 1844]. A Cox proportional hazards model was used to relate survival to both strain and mAb exposure. Monte Carlo simulation was then applied to generate ASN100 exposures for simulated patients given a range of ASN100 doses and infection with each strain (n = 500 per scenario) using a mPBPK model. Using the Cox model, the probability of full protection from toxins (i.e., predicted survival) was estimated for each simulated patient. Results Cox models showed that survival in rabbits is dependent on both strain and ASN100 exposure in lung epithelial lining fluid (ELF). At human doses simulated (360–10,000 mg of ASN100), full or substantial protection is expected for all four strains tested. For the most virulent strain tested in the rabbit pneumonia study (a PVL-negative MSSA, Figure 1), the clinical dose of 3,600 mg of ASN100 provides substantially higher predicted effect relative to lower doses, while doses above 3,600 mg are not predicted to provide significant additional protection. Conclusion A pharmacometric approach allowed for the translation of rabbit survival data to infected patients as well as discrimination of potential clinical doses. These results support the ASN100 dose of 3,600 mg currently being evaluated in a Phase 2 S. aureus pneumonia prevention trial. Disclosures C. M. Rubino, Arsanis, Inc.: Research Contractor, Research support. L. Stulik, Arsanis Biosciences GmbH: Employee, Salary. H. Rouha, 3Arsanis Biosciences GmbH: Employee, Salary. Z. Visram, Arsanis Biosciences GmbH: Employee, Salary. A. Badarau, Arsanis Biosciences GmbH: Employee, Salary. S. A. Van Wart, Arsanis, Inc.: Research Contractor, Research support. P. G. Ambrose, Arsanis, Inc.: Research Contractor, Research support. M. M. Goodwin, Arsanis, Inc.: Employee, Salary. E. Nagy, Arsanis Biosciences GmbH: Employee, Salary.

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A new life model of tripod type Constant Velocity Joint using accelerated life test

Tribology International ◽

10.1016/j.triboint.2018.12.005 ◽

2019 ◽

Vol 132 ◽

pp. 130-141 ◽

Cited By ~ 3

Author(s):

Dong Wan Kim ◽

Seong Han Kim ◽

Chong Nam Chu ◽

Jeong Hyeon Cho

Keyword(s):

Constant Velocity ◽

Accelerated Life Test ◽

Life Test ◽

Constant Velocity Joint ◽

Accelerated Life ◽

Life Model

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Estimating cancer risk in relation to tritium exposure from routine operation of a nuclear-generating station in Pickering, Ontario

Chronic Diseases and Injuries in Canada ◽

10.24095/hpcdp.33.4.06 ◽

2013 ◽

Vol 33 (4) ◽

pp. 247-256 ◽

Cited By ~ 3

Author(s):

S Wanigaratne ◽

E Holowaty ◽

H Jiang ◽

TA Norwood ◽

R Pietrusiak ◽

...

Keyword(s):

Proportional Hazards ◽

Dispersion Model ◽

Atmospheric Dispersion ◽

Female Breast Cancer ◽

Cox Proportional Hazards ◽

Tritium Concentration ◽

Cox Models ◽

Adverse Health Effects ◽

Increased Risk ◽

Risk Of Cancer

Introduction Evidence suggests that current levels of tritium emissions from CANDU reactors in Canada are not related to adverse health effects. However, these studies lack tritium-specific dose data and have small numbers of cases. The purpose of our study was to determine whether tritium emitted from a nuclear-generating station during routine operation is associated with risk of cancer in Pickering, Ontario. Methods A retrospective cohort was formed through linkage of Pickering and north Oshawa residents (1985) to incident cancer cases (1985–2005). We examined all sites combined, leukemia, lung, thyroid and childhood cancers (6–19 years) for males and females as well as female breast cancer. Tritium estimates were based on an atmospheric dispersion model, incorporating characteristics of annual tritium emissions and meteorology. Tritium concentration estimates were assigned to each cohort member based on exact location of residence. Person-years analysis was used to determine whether observed cancer cases were higher than expected. Cox proportional hazards regression was used to determine whether tritium was associated with radiation-sensitive cancers in Pickering. Results Person-years analysis showed female childhood cancer cases to be significantly higher than expected (standardized incidence ratio [SIR] = 1.99, 95% confidence interval [CI]: 1.08–3.38). The issue of multiple comparisons is the most likely explanation for this finding. Cox models revealed that female lung cancer was significantly higher in Pickering versus north Oshawa (HR = 2.34, 95% CI: 1.23–4.46) and that tritium was not associated with increased risk. The improved methodology used in this study adds to our understanding of cancer risks associated with low-dose tritium exposure. Conclusion Tritium estimates were not associated with increased risk of radiation-sensitive cancers in Pickering.

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Breaking the silence about illness and death: Potential effects of a pilot study of the family talk intervention when a parent with dependent children receives specialized palliative home care

Palliative & Supportive Care ◽

10.1017/s1478951521001322 ◽

2021 ◽

pp. 1-7

Author(s):

Megan Weber Falk ◽

Rakel Eklund ◽

Ulrika Kreicbergs ◽

Anette Alvariza ◽

Malin Lövgren

Keyword(s):

Home Care ◽

Family Relationships ◽

Family Members ◽

Family Coping ◽

Open Communication ◽

Entire Family ◽

Palliative Home Care ◽

Dependent Children ◽

Palliative Care Setting ◽

The Family

Abstract Objective The entire family is affected when a parent is severely ill. Parents often need and appreciate professional support when talking to children about illness and death. The family talk intervention (FTI) is family-centered and intends to promote communication about the illness and its consequences, support parenting to enhance family coping and help family members share experiences with each other to create a shared family history. This study aimed to explore potential effects of FTI in specialized palliative home care, as reported by parents. Method This pre-post test intervention pilot was conducted in specialized palliative home care. A convergent mixed-method design was used to analyze interview and questionnaire data. Twenty families with dependent children were recruited from two specialized palliative home care units in Stockholm, Sweden. Results Parents reported that family communication improved after participation in FTI as family members learned communication strategies that facilitated open sharing of thoughts and feelings. Increased open communication helped family members gain a better understanding of each other's perspectives. Parents reported that relationships with their partner and children had improved as they now shared several strategies for maintaining family relationships. Parents were also less worried following participation in FTI. The ill parents stated that they gained a sense of security and were less worried about the future. Significance of results This study adds to the evidence that FTI may be a useful intervention for families with dependent children and an ill parent in a palliative care setting. This trial is registered at ClinicalTrials.gov Identifier NCT03119545.

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Design and application of accelerated life test of grating ruler based on step stress loading

MATEC Web of Conferences ◽

10.1051/matecconf/202133602027 ◽

2021 ◽

Vol 336 ◽

pp. 02027

Author(s):

Jili Wang ◽

Qingyu Li ◽

Xiaocui Zhu ◽

Cheng Gao ◽

Yi Li ◽

...

Keyword(s):

Weibull Distribution ◽

Test Method ◽

Accelerated Life Test ◽

Test Scheme ◽

Life Test ◽

Test Device ◽

Typical Application ◽

Accelerated Life ◽

Life Model ◽

Accelerated Life Model

Combined with the actual project, a grating ruler accelerated life test device is designed, which can simulate the actual loads, including temperature, humidity and speed stress. An accelerated life test scheme based on stepped stress loading is proposed, and 6 grating rulers are tested based on time-censored test method. An accelerated life model based on Weibull distribution used for evaluating the lifetime is established. Related experimental techniques also can be typical application cases for innovative practical teaching.

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