Penalized variable selection in multi-parameter regression survival modeling.

Standard survival models such as the proportional hazards model contain a single regression component, corresponding to the scale of the hazard. In contrast, we consider the so-called "multi-parameter regression" approach whereby covariates enter the model through multiple distributional parameters simultaneously, for example, scale and shape parameters. This approach has previously been shown to achieve flexibility with relatively low model complexity. However, beyond a stepwise type selection method, variable selection methods are underdeveloped in the multi-parameter regression survival modeling setting. Therefore, we propose penalized multi-parameter regression estimation procedures using the following penalties: least absolute shrinkage and selection operator, smoothly clipped absolute deviation, and adaptive least absolute shrinkage and selection operator. We compare these procedures using extensive simulation studies and an application to data from an observational lung cancer study; the Weibull multi-parameter regression model is used throughout as a running example.

An age-structured SEIR model for COVID-19 incidence in Dublin, Ireland with framework for evaluating health intervention cost.

Strategies adopted globally to mitigate the threat of COVID-19 have primarily involved lockdown measures with substantial economic and social costs with varying degrees of success. Morbidity patterns of COVID-19 variants have a strong association with age, while restrictive lockdown measures have association with negative mental health outcomes in some age groups. Reduced economic prospects may also afflict some age cohorts more than others. Motivated by this, we propose a model to describe COVID-19 community spread incorporating the role of age-specific social interactions. Through a flexible parameterisation of an age-structured deterministic Susceptible Exposed Infectious Removed (SEIR) model, we provide a means for characterising different forms of lockdown which may impact specific age groups differently. Social interactions are represented through age group to age group contact matrices, which can be trained using available data and are thus locally adapted. This framework is easy to interpret and suitable for describing counterfactual scenarios, which could assist policy makers with regard to minimising morbidity balanced with the costs of prospective suppression strategies. Our work originates from an Irish context and we use disease monitoring data from February 29th 2020 to January 31st 2021 gathered by Irish governmental agencies. We demonstrate how Irish lockdown scenarios can be constructed using the proposed model formulation and show results of retrospective fitting to incidence rates and forward planning with relevant "what if / instead of" lockdown counterfactuals. Uncertainty quantification for the predictive approaches is described. Our formulation is agnostic to a specific locale, in that lockdown strategies in other regions can be straightforwardly encoded using this model.

Serum uric acid and mortality thresholds among men and women in the Irish health system: A cohort study.

BACKGROUND: Elevation of serum uric acid (SUA) is associated with increased mortality; however, controversy exists regarding the nature of the relationship and differences between men and women. We explored relationships of SUA levels with all-cause mortality in a large cohort of patients within the Irish health system. METHODS: A retrospective cohort study of 26,525 participants was conducted using data from the National Kidney Disease Surveillance System. SUA was modelled in increments of 59.48 µmol/L (1 mg/dL), Cox's proportional hazards model estimated hazard ratios (HRs) and 95% Confidence Intervals (CI), median lifetimes were also computed separately for men and women. Mortality patterns were further explored using penalised splines. RESULTS: There were 1,288 (4.9%) deaths over a median follow-up of 5.1 years. In men, the risk of mortality was greatest for the lowest (<238 µmol/L) and highest (>535 µmol/L) categories [HR 2.35 (1.65-3.14) and HR 2.52 (1.87-3.29) respectively]; the corresponding median lifetimes for men were reduced by 9.5 and 11.7 years respectively compared to the referent. In women, mortality risks were elevated for SUA >416 mol/L [HR 1.69 (1.13-2.47) and beyond; the corresponding median lifetime for women were reduced by 5.9 years compared to the referent. Spline analysis revealed a U-shaped association between SUA and mortality in men, while for women, the pattern of association was J-shaped. CONCLUSION: Mortality patterns attributed to SUA differ between men and women. Optimal survival was associated with SUA concentrations of 304-454 µmol/L for men and < 409 µmol/L for women.