mstate: An R Package for the Analysis of Competing Risks and Multi-State Models

Multi-state models are a very useful tool to answer a wide range of questions in survival analysis that cannot, or only in a more complicated way, be answered by classical models. They are suitable for both biomedical and other applications in which time-to-event variables are analyzed. However, they are still not frequently applied. So far, an important reason for this has been the lack of available software. To overcome this problem, we have developed the mstate package in R for the analysis of multi-state models. The package covers all steps of the analysis of multi-state models, from model building and data preparation to estimation and graphical representation of the results. It can be applied to non- and semi-parametric (Cox) models. The package is also suitable for competing risks models, as they are a special category of multi-state models. This article offers guidelines for the actual use of the software by means of an elaborate multi-state analysis of data describing post-transplant events of patients with blood cancer. The data have been provided by the EBMT (the European Group for Blood and Marrow Transplantation). Special attention will be paid to the modeling of different covariate effects (the same for all transitions or transition-specific) and different baseline hazard assumptions (different for all transitions or equal for some).

Flexible (Polyactive®) versus rigid (hydroxyapatite) dental implants

In a beagle dog study, the peri-implant bone changes around flexible (Polyactive®) and rigid hydroxyapatite (HA) implants were investigated radiographically by quantitative digital subtraction analysis and by assessment of marginal bone height, with the aid of a computerized method. A loss of approximately 1 mm of marginal bone height was observed for both the dense Polyactive and the HA implants, after 6 months of loading. This value appeared to be stable from 12 weeks of loading onward. Along the total length of the implant during the first 6 weeks of loading, both the flexible (dense Polyactive) and the rigid (HA) implants showed a decrease in density. However, after this 6-week period, the bone density around the implants increased, and after 18 weeks the original bone density was reached. The flexible Polyactive implants provoked less decrease in density than the rigid HA implants, although not to a statistically significant level. This finding sustains the hypothesis that flexible implant materials may transfer stresses to the surrounding bone more favorably

Unfolding tragedies: the impact of a mother's death on her kin and community. An ethnography from Southern Malawi.

In examining the specific impact of a mother's death on her surviving family and community, the thesis highlights the social devastation resulting from such an event. Crucially, it argues that the increased frequency of maternal death associated with the HIV/AIDS epidemic, and the associated increase in numbers of orphaned children, have the potential to provoke full-scale destruction of traditional kinship structures and coping mechanisms. The study contributes to a gendered study of death and the resultant coping mechanisms as well as emphasizing the importance of sibling bonds in Malawian kinship. Furthermore, it provides an analysis of the current trends relating to orphan care, and suggests how these goals could be improved within the specific cultural context. The findings are based on 14 months of in situ fieldwork, during which time a totla of 78 interviews were conducted with 66 individuals, 46 of whom are case studies. Further interviews were conducted with hospital personnel, workers with orphans, and teachers, i.e. those in positions to provide social commentary. Nudist N4 software was used for data management of the interview transcripts and fieldnotes, and facilitated access to the coded data as analysis proceeded. An historical understanding of Malawi's cultural context is outlined in the introductory chapter and the entire discussion is grounded within this context. More detailed anthropological data is provided in the chapter on kinship, which emphasizes the importance of maternal kin in looking after orphans subsequent to a mother's death. Chapters on HIV and death outline how communities are besieged by illnesses surrounding HIV-infection, and how the increased death rates associated with HIV have undermined the traditional bereavement processes, and, hence, the associated coping mechanisms. The thesis concludes with a discussion of the kinds of orphan care currently available in Malawi, followed by recommendations on how the needs of orphans could better be met by development initiatives that are more suited to working with community-based organizations.sub_iihdunpub906_ethesesunpu

Popular music lyrics and the COVID-19 pandemic

A limited amount of previous research suggests that deteriorating socioeconomic conditions may be associated with greater popularity of music lyrics featuring negative emotional content and references to relationships. The present research considered this in charting popular music before and during the first six months of the COVID-19 pandemic. A dataset based on the song lyrics of the top-5 charting weekly songs in the UK and USA from January 1999 to August 2020 was computer-analysed for interpersonal variables, such as satisfaction and human interest, and positive and negative emotional valence. Results indicated lower satisfaction and human interest in lyrics in the USA and UK in the first six months of the COVID-19 pandemic compared to the lyrics in charting songs in 2015-2019. The USA charting songs in 2020 also saw higher leveling and negative emotional content; and, when considering monthly data from 1999-2020, there was a positive association between economic misery and the number of negatively-valenced words. The findings broaden our understanding of the relationship between significant global events and trends in popular music

Non-parametric estimation of transition probabilities in non-Markov multi-state models: The landmark Aalen-Johansen estimator

Development and application of statistical models for medical scientific researc

Dynamic predicting by landmarking as an alternative for multi-state modeling: an application to acute lymphoid leukemia data

This paper considers the problem of obtaining a dynamic prediction for 5-year failure free survival after bone marrow transplantation in ALL patients using data from the EBMT, the European Group for Blood and Marrow Transplantation. The paper compares the new landmark methodology as developed by the first author and the established multi-state modeling as described in a recent Tutorial in Biostatistics in Statistics in Medicine by the second author and colleagues. As expected the two approaches give similar results. The landmark methodology does not need complex modeling and leads to easy prediction rules. On the other hand, it does not give the insight in the biological processes as obtained for the multi-state model

Parametric hazard rate models for long-term sickness absence

PURPOSE: In research on the time to onset of sickness absence and the duration of sickness absence episodes, Cox proportional hazard models are in common use. However, parametric models are to be preferred when time in itself is considered as independent variable. This study compares parametric hazard rate models for the onset of long-term sickness absence and return to work. METHOD: Prospective cohort study on sickness absence with four follow-up years of 53,830 employees working in the private sector in the Netherlands. The time to onset of long-term (>6 weeks) sickness absence and return to work were modelled by parametric hazard rate models. RESULTS: The exponential parametric model with a constant hazard rate most accurately described the time to onset of long-term sickness absence. Gompertz-Makeham models with monotonically declining hazard rates best described return to work. CONCLUSIONS: Parametric models offer more possibilities than commonly used models for time-dependent processes as sickness absence and return to work. However, the advantages of parametric models above Cox models apply mainly for return to work and less for onset of long-term sickness absence

ABC-SysBio—approximate Bayesian computation in Python with GPU support

Motivation: The growing field of systems biology has driven demand for flexible tools to model and simulate biological systems. Two established problems in the modeling of biological processes are model selection and the estimation of associated parameters. A number of statistical approaches, both frequentist and Bayesian, have been proposed to answer these questions

The impact of loco-regional recurrences on metastatic progression in early-stage breast cancer: a multistate model

To study whether the effects of prognostic factors associated with the occurrence of distant metastases (DM) at primary diagnosis change after the incidence of loco-regional recurrences (LRR) among women treated for invasive stage I or II breast cancer. The study population consisted of 3,601 women, enrolled in EORTC trials 10801, 10854, or 10902 treated for early-stage breast cancer. Data were analysed in a multivariate, multistate model by using multivariate Cox regression models, including a state-dependent covariate. The presence of a LRR in itself is a significant prognostic risk factor (HR: 3.64; 95%-CI: 2.02-6.5) for the occurrence of DM. Main prognostic risk factors for a DM are young age at diagnosis (</=40: HR: 1.79; 95%-CI: 1.28-2.51), larger tumour size (HR: 1.58; 95%-CI: 1.35-1.84) and node positivity (HR: 2.00; 95%-CI: 1.74-2.30). Adjuvant chemotherapy is protective for a DM (HR: 0.66; 95%-CI: 0.55-0.80). After the occurrence of a LRR the latter protective effect has disappeared (P = 0.009). The presence of LRR in itself is a significant risk factor for DM. For patients who are at risk of developing LRR, effective local control should be the main target of therapy

Corrigendum to “Authors’ reply—Does the RAPIDO trial suggest a benefit of post-operative chemotherapy after preoperative chemoradiation in rectal cancer? No, it does not”: [ESMO Open 8 (2023) 101645]

The authors regret that in the original publication reference 1 was given in correctly. The correct reference is as follows: 1. J. Socha, W. Michalski, K. Bujko, Does the RAPIDO trial suggest a benefit of post-operative chemotherapy after preoperative chemoradiation in rectal cancer? No, it does not., ESMO Open, Volume 8, Issue 5, 2023, 101644, https://doi.org/10.1016/j.esmoop.2023.101644The authors would like to apologise for any inconvenience caused.</p