hazard models
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H-INDEX

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2022 ◽  
Author(s):  
Marwa Elsaeed Elhefnawy ◽  
Siti Maisharah Sheikh Ghadzi ◽  
Orwa Albitar ◽  
Balamurugan Tangiisuran ◽  
Hadzliana Zainal ◽  
...  

Abstract There are established correlation between risk factors and the recurrence of ischemic stroke (IS), however does the hazard of recurrent IS change although without the influence of established risk factors? This study aimed to quantify the hazard of recurrent IS at different time points after the index IS. This was a population cohort study extracted data of 7697 patients with a history of first IS attack registered with National Neurology Registry of Malaysia. A repeated time to recurrent IS model was developed using NONMEM version 7.5. Three baseline hazard models were fitted into the data. The best model was selected using maximum likelihood estimation, clinical plausibility and visual predictive checks. Three hundred and thirty-three (4.32%) patients developed at least one recurrent IS within the maximum 7.37 years follow-up. In the absence of significant risk factors, the hazard of recurrent IS was predicted to be 0.71 within the first month after the index IS and reduced to 0.022 between the first to third months after the index attack. The hazard of IS recurrence accelerated with the presence of typical risk factors such as hyperlipidaemia (HR, 2.64 [2.10-3.33]), hypertension (HR, 1.97 [1.43-2.72], and ischemic heart disease (HR, 2.21 [1.69-2.87]). In conclusion, the absence of significant risk factors, predicted hazard of recurrent IS was prominent in the first month after the index IS and was non-zero even three months after the index IS or later. Optimal secondary preventive treatment should incorporate the ‘nature risk’ IS recurrence.


2021 ◽  
pp. 003288552110693
Author(s):  
Thomas W. Wojciechowski

This study sought to understand how PTSD predicts opioid use onset rates and how subsequent exposures to violence also influence this risk following adjudication. Survival analysis was used to examine the moderating role that baseline PTSD status plays for predicting rates of opioid use onset risk following adjudication. Hazard models used to examine the role of time-varying covariates for predicting opioid onset risk following adjudication. PTSD was found to predict significantly greater odds of opioid use initiation. Hazard of introducing opioid use was greater during observation periods in which participants witnessed violence. This effect was greater for PTSD sufferers.


Volcanica ◽  
2021 ◽  
Vol 4 (2) ◽  
pp. 325-343
Author(s):  
Elisabeth Gallant ◽  
Lawrence Cole ◽  
Charles Connor ◽  
Amy Donovan ◽  
Danielle Molisee ◽  
...  

Vent opening hazard models are routinely used as inputs for assessing distal volcanic hazards (lava flows, tephra fallout) in distributed volcanic fields. These vent opening hazard models have traditionally relied on the location of mapped vents; seldom have they taken into account how vents are linked in space and time. We show that inputs needed to appropriately model distal hazards are fundamentally different than thoses required to model near-vent hazards (ground deformation). We provide a computational model to obtain more appropriate eruptive source parameters (ESPs) for distal volcanic hazard sources and show the utility of our code through three examples. The code's strength is that it links events based on the spatio-temporal relationships of vents through heirarchical clustering. The development of the code and its strenghts and weaknesses are discussed. This work challenges previous ideas about ESPs and we hope this work leads to further improvement in hazard assessment methods.


Author(s):  
Jan Saarela ◽  
Maria Stanfors ◽  
Mikael Rostila

The literature on health dependencies among partners typically ignores diversity of partnership characteristics. One salient example is the ethnic composition. We extend prior work on partnerships and health by investigating how married and cohabiting partners mutually influence each other’s receipt of health-related benefits, focusing on how such correlations vary with the couple’s ethnic composition. We study partners’ mutual receipt of sickness allowance and disability pension in ethnically endogamous and exogamous couples in Finland. The population consists of native individuals in similar socioeconomic positions but belonging to two different ethnic groups—Finnish and Swedish speakers—who differ in health and family life. Using data from population registers, we estimate discrete-time hazard models for first-time benefit receipt, as related to partner’s benefit receipt, among midlife couples. We found evidence of mutual receipt of health benefits in both endogamous and exogamous couples, the correlation being strongest for disability pension. Partner correlation in disability pension receipt is slightly stronger in endogamous Swedish than in endogamous Finnish couples, while women in exogamous couples are slightly less sensitive to men’s receipt than vice versa. The results show that mutual health may be heterogeneous across couples that differ in ethnic composition.


2021 ◽  
pp. 1471082X2110626
Author(s):  
Heather L. Turner ◽  
Andy D. Batchelor ◽  
David Firth

We propose a hazard model for entry into marriage, based on a bell-shaped function to model the dependence on age. We demonstrate near-aliasing in an extension that estimates the support of the hazard and mitigate this via re-parameterization. Our proposed model parameterizes the maximum hazard and corresponding age, thereby facilitating more general models where these features depend on covariates. For data on women's marriages from the Living in Ireland Surveys 1994–2001, this approach captures a reduced propensity to marry over successive cohorts and an increasing delay in the timing of marriage with increasing education.


BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Fanny Petermann-Rocha ◽  
Donald M. Lyall ◽  
Stuart R. Gray ◽  
Jason M. R. Gill ◽  
Naveed Sattar ◽  
...  

Abstract Background Previous cohort studies have investigated the relationship between self-reported physical activity (PA) and dementia. Evidence from objective device-measured PA data is lacking. This study aimed to explore the association of device-measured PA with the risk of dementia incidence and common subtypes (Alzheimer’s disease [AD] and vascular dementia) using the UK Biobank study. Methods 84,854 participants (55.8% women), invited to participate in the device-measured PA between 2013 and 2015, were included in this prospective cohort study. Wrist accelerometers were used to measure light, moderate, vigorous, moderate-to-vigorous PA (MVPA) and total PA intensity and duration (MET/min/week). Incident dementia (fatal and non-fatal) was extracted from hospital episodes records for incidence and death register for mortality. Incidence follow-up was carried out until the end of March 2021in England and Scotland and the end of March 2018 in Wales. Mortality data were available until February 2021. Nonlinear associations were first investigated using penalised cubic splines fitted in the Cox proportional hazard models. In addition, using MVPA, five categories were created. Associations of these categories with the outcomes were investigated using Cox proportional hazard models. Analyses were adjusted for sociodemographic, lifestyle and health-related factors. Results After a median follow-up of 6.3 years, 678 individuals were diagnosed with dementia. Evidence of nonlinearity was observed for all PA modes and all-cause dementia. For categories of MVPA, there was a significant trend towards a low risk of overall dementia when higher levels of MVPA were achieved (HRtrend 0.66 [95% CI 0.62 to 0.70]. The lowest risk was identified in individuals who performed more than 1200 MET/min/week, those who had 84% (95% CI 0.12 to 0.21) lower risk of incident dementia compared to those who performed < 300 MET/min/week. Conclusions Participants with higher PA levels had a lower risk of incident dementia than those less active, independently of sociodemographic, lifestyle factors and comorbidity. Considering that the majority of previous studies have reported this association using self-reported data, our findings highlight the strong inverse association between PA objectively measured and incident dementia.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 336-337
Author(s):  
Yurun Cai ◽  
Jacek Urbanek ◽  
David Roth ◽  
Jeremy D Walston ◽  
Karen Bandeen-Roche ◽  
...  

Abstract Low physical activity (PA) is a common phenotype of frailty, but whether disengagement of daily lifestyle PA signals impending frailty remains unexplored. Using STURDY (Study to Understand Fall Reduction and Vitamin D in You) data from 499 robust/prefrail adults (mean age=76 + 5 years; 42% women), we examined whether accelerometer patterns (activity counts/day, active minutes/day, and activity fragmentation) were prospectively associated with incident frailty over 2 years of follow-up; 48 (10%) participants developed frailty. In Discrete-Cox hazard models adjusted for demographics, medical conditions, and device wear days, every 30 min/day higher baseline active time, 100,000 more activity counts/day, and 1% lower activity fragmentation was associated with a 13% (p=0.003), 10% (p=0.001), and 8% (p&lt;0.001) lower risk of frailty, respectively. Our results show that both reduced amounts and fragmented patterns of daily PA captured from accelerometry are associated with phenotypic frailty and might signal frailty onset.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3456-3456
Author(s):  
Vivek M. Shastri ◽  
Lata Chauhan ◽  
Todd A. Alonzo ◽  
Yi-Cheng Wang ◽  
Richard Aplenc ◽  
...  

Abstract Gemtuzumab Ozogamicin (GO) is a CD33-directed antibody conjugated to calicheamicin used in AML immunotherapy. Children's Oncology Group led pediatric AML phase II trial COG-AAML03P1 (NCT00070174) established that GO could be safely added to the standard chemotherapy regimen consisting of ara-C, daunorubicin and etoposide (ADE+GO) and improved outcome(Cooper et al., 2012). Subsequent COG-AAML0531 phase III trial (NCT00372593) randomized patients to receive either standard chemotherapy alone (ADE) or with addition of two doses of GO (ADE+GO) and showed that addition of GO improved outcome in newly diagnosed AML patients (Gamis et al., 2014). Our group previously established that CD33 genetic variation impacts GO response in AML patients (Lamba et al., 2017). Given that the antileukemic effect of GO is primarily driven by calicheamicin induced DNA damage, in this study we investigated pharmacogenomic impact of SNPs in DNA damage response (DDR) pathway genes on GO treatment response. We genotyped 132 SNPs in 42 genes involved in DNA damage repair pathway in DNA samples from 470 patients treated with standard chemotherapy in AAML0531 trial (ADE arm) and 755 patients treated with addition of GO to standard therapy in AAML03P1 and AAAML0531 trials (ADE+GO arm). Univariate analysis to test for association between OS, EFS, DFS and RR after induction 1 in both ADE+GO and ADE arms identified 20 SNPs in 16 genes that were significantly associated with at least one of the clinical endpoints tested in the only ADE+GO arm but not in ADE arm of the trials. We tested these 20 SNPs in all possible combinations with a maximum of 3 SNP/model using multivariable Cox proportional hazard models for association with EFS and OS in patients treated with ADE+GO. Drastically increased number of models arising from higher SNP combination numbers was a computational challenge thus we restricted our analysis to a maximum of 3 SNP combinations. We performed 1000 permutation tests per model to determine the likelihood of obtaining them falsely. Models were ordered according to their Bayesian Information Criterion (BIC) and weight in favor of each model. Those withleast BIC and a 1000 permutation p≤0.05 were selected for development of DDR pharmacogenomics score. DDR_PGx8 score was defined by adding the genotype scores of 8 SNPs in 7 genes (AKT1, ATR, DDB2, PARP1, PI3KCA, PTEN and RAD51) accounting for mode of inheritance (additive, dominant or recessive) and direction of their association with outcome (positive for beneficial and negative for detrimental association) Fig 1A shows overall study design. The DDR_PGx8 score ranged from -5 to 3 in patients treated with ADE+GO (n=755) or ADE alone (N=470). Based on the distribution, the scores were stratified into high (score ≥0, n=212 in ADE group and n=357 in ADE+GO group) and low score (score &lt;0, n=241 in ADE group and n=329 in ADE+GO group) groups. The distribution of DDR_PGx8 score groups did not differ by risk groups or MRD1 status. However, it differed significantly within race with 81.81% (108/132) of black or African American patients compared to 43.75% (364/832) of white patients in the low DDR_PGx8 score group. Patients with low-DDR-PGx8 score had significantly worse EFS (HR=1.52, 95%CI (1.22-1.90), p&lt;0.001; Fig 1B), OS (HR=1.62, 95%CI(1.24-2.11), p&lt;0.001), DFS (HR=1.88, 95%CI(1.42-2.50), p&lt;0.00001;), and higher RR1 (HR=1.89, 95%CI(1.40-2.40), p&lt;0.00001) compared to high-DDR-PGx8 score patients when treated with GO (ADE+GO cohort). This impact of DDR_PGx8 was not observed in patients treated with standard chemotherapy alone (ADE arm), with no difference between low and high DDR_PGx8 score groups in EFS (Fig 1B), OS, DFS and RR (all p&gt;0.28). In multivariable Cox proportional hazard models for DDR-PGx8 score groups, initial risk group assignment, WBC at diagnosis and age, low-DDR-PGx8 score remained a significant and independent predictor of inferior EFS (HR=1.6, 95%CI=1.21-2.02, p&lt;0.001; Fig 1C) and OS (HR=1.6, 95%CI=1.17-2.22, p=0.003) in ADE+GO arm but not in ADE arm. We establish a DNA damage repair response-based pharmacogenomics score predicting outcome in patients treated with addition of GO to standard chemotherapy. The score was not predictive of outcome in patients treated with standard chemotherapy alone implying its impact is GO-specific. Our results in conjunction with existing CD33 SNPs provide a rationale for use of pharmacogenomics in personalizing GO treatment. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
James Nguyen ◽  
Jonathan Weber ◽  
Brittany Hsu ◽  
Rajasekhar R. Mulyala ◽  
Lin Wang ◽  
...  

AbstractLeft atrial (LA) features are altered when diastolic dysfunction (DD) is present. The relations of LA features to the DD severity and to adverse outcomes remain unclear using CMR images. We sought to compare LA features including volumes, emptying fraction, and strains as predictors of left ventricular (LV) DD and adverse outcomes. We compared four groups including normal controls (n = 32), grade I DD (n = 69), grade II DD (n = 42), and grade III DD (n = 21). DD was graded by echocardiography following the current ASE guidelines. Maximum LA volume (LAVmax), minimum LA volume (LAVmin), and LA emptying fraction (LAEF) were assessed using CMR cine images. Phasic LA strains including reservoir, conduit, and booster pump strain were assessed by feature tracking. The outcome was a composite of hospital admissions for heart failure and all-cause mortality analyzed using Cox proportional hazard models. LAVmax and LAVmin were progressively larger while LAEF and LA strain measures were lower with worsening degree of DD (all p < 0.001). Among 132 patients with DD, 61 reached the composite outcome after on average 36-months of follow-up. Each of the LA parameters except for LA conduit strain was an independent predictor of the outcome in the adjusted Cox proportional hazard models (all p < 0.001). They remained significant outcome predictors after the model additionally adjusted for LV longitudinal strain. The AUC of outcome prediction was highest by LAEF (0.760) followed by LA reservoir strain (0.733) and LAVmin (0.725). Among all the LA features, increased LA volumes, reduced LAEF, reduced LA reservoir and booster pump strains were all associated with DD and DD severity. While LA strains are valuable, conventional parameters such as LAEF and LAVmin remain to be highly effective in outcome prediction with comparable performance.


2021 ◽  
Vol 3 (2) ◽  
pp. 1-19
Author(s):  
Peter Enesi Omaku ◽  
Benjamin Agboola Oyejola

Spatial effects are often simultaneously investigated with non-linear effects of continuous covariates and the usual linear effect. In this work the performance of models with and without spatial dependence in partitioned (PM) and non-partitioned models (NPM) for four (4) censoring percentages, three(3) levels of Weibull baseline variances (WBV), and sample sizes 100, 500 & 1000 were investigated. Hazard models were adapted to the generalized additive predictors and analyses were carried out via MCMC simulation technique. The performances of the models were again assessed when fitted to the diabetic data set. Results suggest that; partition models outperformed the non-partition ones. Models with spatial dependence perform better than models without spatial dependence in denser event times and when WBVs are low. The partition models perform better with spatial dependence than the Non-partitioned models. For the diabetic data set, it is seen that covariates Age and Blood Sugar level (BSL) violates the proportionality assumptions upon test. Further assessment from the graph of coefficient against time; suggest that Age be put to cut-points while BSL was estimated for models with and without Penalized splines for the sake of comparison, since the graph shows just a slight deviation from proportionality. Hazard rates for the time varying Age; indicate that as the time of study rolls by, the hazard of experiencing the event death from the disease increases steadily between intervals but constant within each time interval. A unit change in hazard rate for BSL indicates a decrease for PM implemented for with and without penalized splines. The model without penalized splines was however, seen to be better with smaller DIC (Deviance Information Criteria) value. Marriage is seen to be significant in the management of the disease in comparison to single patients. In addition patients are advised to visit their physicians on a regular basis to run a routine check to keep their BSL in good range. The study provides a means of moving out of non-linear ruts in survival data analysis. Intervals increase sample sizes (pseudoobservations), which in turn improves the modified Partitioned model when they are with or without spatial dependence.


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