Semiparametric Competing Risks Regression Under Interval Censoring Using the R Package intccr

Background and objective: Competing risk data are frequently interval-censored in real-world applications, that is, the exact event time is not precisely observed but is only known to lie between two time points such as clinic visits. This type of data requires special handling because the actual event times are unknown. To deal with this problem we have developed an easy-to-use open-source statistical software. Methods: An approach to perform semiparametric regression analysis of the cumulative incidence function with interval-censored competing risks data is the sieve maximum likelihood method based on B-splines. An important feature of this approach is that it does not impose restrictive parametric assumptions. Also, this methodology provides semiparametrically efficient estimates. Implementation of this methodology can be easily performed using our new R package intccr. Results: The R package intccr performs semiparametric regression analysis of the cumulative incidence function based on interval-censored competing risks data. It supports a large class of models including the proportional odds and the Fine-Gray proportional subdistribution hazards model as special cases. It also provides the estimated cumulative incidence functions for a particular combination of covariate values. The package also provides some data management functionality to handle data sets which are in a long format involving multiple lines of data per subject. Conclusions: The R package intccr provides a convenient and flexible software for the analysis of the cumulative incidence function based on interval-censored competing risks data

Building Prediction Models for Dementia: The Need to Account for Interval Censoring and the Competing Risk of Death

Indiana University-Purdue University Indianapolis (IUPUI)Context. Prediction models for dementia are crucial for informing clinical decision making in older adults. Previous models have used genotype and age to obtain risk scores to determine risk of Alzheimer’s Disease, one of the most common forms of dementia (Desikan et al., 2017). However, previous prediction models do not account for the fact that the time to dementia onset is unknown, lying between the last negative and the first positive dementia diagnosis time (interval censoring). Instead, these models use time to diagnosis, which is greater than or equal to the true dementia onset time. Furthermore, these models do not account for the competing risk of death which is quite frequent among elder adults. Objectives. To develop a prediction model for dementia that accounts for interval censoring and the competing risk of death. To compare the predictions from this model with the predictions from a naïve analysis that ignores interval censoring and the competing risk of death. Methods. We apply the semiparametric sieve maximum likelihood (SML) approach to simultaneously model the cumulative incidence function (CIF) of dementia and death while accounting for interval censoring (Bakoyannis, Yu, & Yiannoutsos, 2017). The SML is implemented using the R package intccr. The CIF curves of dementia are compared for the SML and the naïve approach using a dataset from the Indianapolis Ibadan Dementia Project. Results. The CIF from the SML and the naïve approach illustrated that for healthier individuals at baseline, the naïve approach underestimated the incidence of dementia compared to the SML, as a result of interval censoring. Individuals with a poorer health condition at baseline have a CIF that appears to be overestimated in the naïve approach. This is due to older individuals with poor health conditions having an elevated risk of death. Conclusions. The SML method that accounts for the competing risk of death along with interval censoring should be used for fitting prediction/prognostic models of dementia to inform clinical decision making in older adults. Without controlling for the competing risk of death and interval censoring, the current models can provide invalid predictions of the CIF of dementia

Risk of Lower Extremity Amputation Revision in Patients with Peripheral Vascular Disease Adjusting for a Competing Risk of Death

Indiana University-Purdue University Indianapolis (IUPUI)Objectives: The aims of this study are to estimate the cumulative incidence of lower extremity amputation (LEA) revision and reamputation adjusting for a competing risk of death, estimate the one-year event-free mortality rates for patients with peripheral vascular disease undergoing LEA, and develop predictive models for LEA revision and reamputation adjusting for a competing risk of death. Methods: This was a retrospective review of the prospectively collected Vascular Quality Initiative (VQI) registry between 2013 and 2018. Adults undergoing unilateral LEA were included. Demographics, comorbidities, medications, smoking status, history of vascular procedures and revascularization attempts, and procedure urgency were considered. Models to predict LEA revision and reamputation were developed using multivariable regression on the interval-censored competing risks data using semiparametric regression on the cumulative incidence function. Results: The cumulative incidences of LEA revision and revision-free mortality within one year of index amputation are 14.9% and 15.5% respectively. Patient BMI, smoking status, aspirin use, history of revascularization, and level of planned LEA are significantly associated with the odds of LEA revision. Age, amputation urgency, dialysis, and level of planned LEA are associated with the one-year odds of revision-free mortality. A patient receiving an index above knee amputation (AKA) has 61% lower odds of LEA revision (p < 0.0001) but 51% higher odds of revision-free mortality following LEA (p < 0.0001). Previous revascularization procedures increase the odds of revision by 23% (p < 0.0001). The cumulative incidences of reamputation and one-year reamputation-free mortality following LEA are 11.5% and 16.9% respectively. Urgency of the procedure, history of revascularization procedures, and level of planned LEA are statistically associated with the odds of reamputation when adjusting for the competing risk of death. Patients receiving index AKA have 62% lower odds of reamputation (p < 0.0001) compared to BKA. Dialysis is the strongest predictor of one-year mortality (OR 2.576, p < 0.0001). Conclusions: Patients with appropriately managed PVD, which still progresses to amputation have higher odds of LEA revision and reamputation. Revision risk can be predicted and compared on the basis of patient factors and the planned index amputation

An epidemiologic investigation of wastage and productivity of ewes in a sample of New Zealand commercial flocks : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Veterinary Science at Massey University, Palmerston North, New Zealand

Material in this thesis has been published as: K.J.Griffiths, AL Ridler, C Heuer, RA Corner-Thomas & PR Kenyon. (2016, Dec). The effect of liveweight and body condition score on the ability of ewe lambs to successfully rear their offspring. Small Ruminant Research, 145, 130-135. https://doi.org/10.1016/j.smallrumres.2016.11.001 KJ Griffiths, AL Ridler, C Heuer, RA Corner-Thomas & PR Kenyon. (2018). Associations between liveweight, body condition score and previous reproductive outcomes, andthe risk of ewes bred at 18-months of age being dry at docking, New Zealand Veterinary Journal, 66(6), 290-296. https://doi.org/10.1080/00480169.2018.1498035 KJ Griffiths, AL Ridler, CWR Compton, RA Corner-Thomas & PR Kenyon. (2019.) Investigating associations between lamb survival to weaning and dam udder and teatscores, New Zealand Veterinary Journal, 67(4), 163-171. https://doi.org/10.1080/00480169.2019.1596523 KJ Griffiths, AL Ridler, CWR Compton, RA Corner-Thomas & PR Kenyon. (2019). Associations between lamb growth to weaning and dam udder and teat scores, New Zealand Veterinary Journal, 67(4), 172-179. https://doi.org/10.1080/00480169.2019.1596524Until recently, little was known about ewe wastage in commercial New Zealand ewe flocks, or indeed, internationally. This PhD was undertaken with the broad objective of establishing the extent, timing and cause (premature culling or mortality) of ewe wastage in New Zealand ewe flocks, while also identifying factors associated with increased ewe wastage including pre-mating body condition score (BCS), failure to rear a lamb and, linked with the latter, impact of ewe udder defects on productivity. To the authors’ knowledge, this is the first study that reports both lifetime wastage and detailed annual wastage in a sample of New Zealand commercial flocks. Of the 13,142 enrolled ewes, 50.4% exited their respective flocks due to premature culling (where a ewe is culled from the flock prior to the potential end of her productive lifespan) and 40.0% due to on-farm dead/missing, giving a total of 90.4% that exited due to wastage. In all years, pre-mating BCS could be used as a predictor of ewe wastage with odds of wastage lower with increasing BCS. In Year 1, wastage for each cohort ranged from 7.6% - 45.4% of ewe lambs enrolled, while wastage due to dead/missing accounted for 26.8% - 100.0% of ewe lamb wastage across cohorts, and premature culling was primarily due to poor reproductive performance (dry at pregnancy diagnosis or dry at docking when 3-6-week-old lambs are yarded for ear marking, tail removal and castration of males). Hence, other than the cull sale-value for those that were prematurely culled, the farmer received no productive or economic benefit from these wasted ewe lambs. Ewe lambs with heavier conceptus adjusted liveweight (CALW) and those that gained greater CALW between pregnancy diagnosis and pre-lambing were less likely to be dry at docking. Similarly, for two-tooth ewes (18-months of age at breeding), heavier ewes and those that gained CALW were less likely to be dry at docking than lighter ewes or those that lost CALW. Pre-mating udder palpation scores of hard or lump were associated with increased odds of lambs not surviving to weaning compared with normal scores. Additionally, surviving offspring of ewes with pre-mating udder palpation scores of hard had lower growth to weaning. Commercial farmers can use the information presented in this thesis to identify ewes within their flocks that have increased risk of wastage or poor productivity. They can then alter management of these at-risk ewes to both improve ewe productivity and reduce likelihood of wastage