MSMpred: interactive modelling and prediction of individual evolution via multistate models.

Background: Modelling the course of a disease regarding severe events and identifying prognostic factors is of great clinical relevance. Multistate models (MSM) can be used to describe diseases or processes that change over time using different states and the transitions between them. Specifically, they are useful to analyse a disease with an increasing degree of severity, that may precede death.

Characteristics and Outcomes by Ceiling of Care of Subjects Hospitalized with COVID-19 During Four Waves of the Pandemic in a Metropolitan Area: A Multicenter Cohort Study.

Introduction: The profiles of patients with COVID-19 have been widely studied, but little is known about differences in baseline characteristics and in outcomes between subjects with a ceiling of care assigned at hospital admission and subjects without a ceiling of care. The aim of this study is to compare, by ceiling of care, clinical features and outcomes of hospitalized subjects during four waves of COVID-19 in a metropolitan area in Catalonia.

Methods: Observational study conducted during the first (March-April 2020), second (October-November 2020), third (January-February 2021), and fourth wave (July-August 2021) of COVID-19 in five centers of Catalonia.

SARS-Cov-2 incubation period according to vaccination status during the fifth COVID-19 wave in a tertiary-care center in Spain: a cohort study.

Background: The incubation period of an infectious disease is defined as the elapsed time between the exposure to the pathogen and the onset of symptoms. Although both the mRNA-based and the adenoviral vector-based vaccines have shown to be effective, there have been raising concerns regarding possible decreases in vaccine effectiveness for new variants and variations in the incubation period.

Methods: We conducted a unicentric observational study at the Hospital Universitari de Bellvitge, Barcelona, using a structured telephone survey performed by trained interviewers to estimate the incubation period of the SARS-CoV-2 Delta variant in a cohort of Spanish hospitalized patients.

Circulating carotenoids are associated with favorable lipid and fatty acid profiles in an older population at high cardiovascular risk.

Carotenoid intake has been reported to be associated with improved cardiovascular health, but there is little information on actual plasma concentrations of these compounds as biomarkers of cardiometabolic risk. The objective was to investigate the association between circulating plasma carotenoids and different cardiometabolic risk factors and the plasma fatty acid profile. This is a cross-sectional evaluation of baseline data conducted in a subcohort (106 women and 124 men) of an ongoing multi-factorial lifestyle trial for primary cardiovascular prevention.

A class of two-sample nonparametric statistics for binary and time-to-event outcomes.

We propose a class of two-sample statistics for testing the equality of proportions and the equality of survival functions. We build our proposal on a weighted combination of a score test for the difference in proportions and a weighted Kaplan-Meier statistic-based test for the difference of survival functions. The proposed statistics are fully non-parametric and do not rely on the proportional hazards assumption for the survival outcome.

Using the geometric average hazard ratio in sample size calculation for time-to-event data with composite endpoints.

Background: Sample size calculation is a key point in the design of a randomized controlled trial. With time-to-event outcomes, it's often based on the logrank test. We provide a sample size calculation method for a composite endpoint (CE) based on the geometric average hazard ratio (gAHR) in case the proportional hazards assumption can be assumed to hold for the components, but not for the CE.

Design of phase III trials with long-term survival outcomes based on short-term binary results.

Pathologic complete response (pCR) is a common primary endpoint for a phase II trial or even accelerated approval of neoadjuvant cancer therapy. If granted, a two-arm confirmatory trial is often required to demonstrate the efficacy with a time-to-event outcome such as overall survival. However, the design of a subsequent phase III trial based on prior information on the pCR effect is not straightforward.

HIVconsv Vaccines and Romidepsin in Early-Treated HIV-1-Infected Individuals: Safety, Immunogenicity and Effect on the Viral Reservoir (Study BCN02).

Kick&kill strategies combining drugs aiming to reactivate the viral reservoir with therapeutic vaccines to induce effective cytotoxic immune responses hold potential to achieve a functional cure for HIV-1 infection. Here, we report on an open-label, single-arm, phase I clinical trial, enrolling 15 early-treated HIV-1-infected individuals, testing the combination of the histone deacetylase inhibitor romidepsin as a latency-reversing agent and the MVA.HIVconsv vaccine.

A nonparametric test for the association between longitudinal covariates and censored survival data.

Many biomedical studies focus on the association between a longitudinal measurement and a time-to-event outcome while quantifying this association by means of a longitudinal-survival joint model. In this article we propose using the $LLR$ test - a longitudinal extension of the log-rank test statistic given by Peto and Peto (1972) - to provide evidence of a plausible association between a time-to-event outcome (right- or interval-censored) and a time-dependent covariate. As joint model methods are complex and hard to interpret, it is wise to conduct a preliminary test such as $LLR$ for checking the association between both processes.

A new approach for sizing trials with composite binary endpoints using anticipated marginal values and accounting for the correlation between components.

Composite binary endpoints are increasingly used as primary endpoints in clinical trials. When designing a trial, it is crucial to determine the appropriate sample size for testing the statistical differences between treatment groups for the primary endpoint. As shown in this work, when using a composite binary endpoint to size a trial, one needs to specify the event rates and the effect sizes of the composite components as well as the correlation between them.

Selection of composite binary endpoints in clinical trials.

The choice of a primary endpoint is an important issue when designing a clinical trial. It is common to use composite endpoints as a primary endpoint because it increases the number of observed events, captures more information and is expected to increase the power. However, combining events that have no similar clinical importance and have different treatment effects makes the interpretation of the results cumbersome and might reduce the power of the corresponding tests.

Estimation and residual analysis with R for a linear regression model with an interval-censored covariate.

Interval-censored covariates are sometimes encountered in longitudinal studies and considered as possible predictors in a regression model. This paper, motivated by an AIDS study, proposes an implementation in R for the estimation of parameters and the assessment of the assumptions of a linear regression model with an interval-censored covariate. The properties of the parameters estimators and the behavior of three proposed residuals are addressed through two simulation studies.

[Two methods to analyze trends in the incidence of heroin and cocaine use in Barcelona [Spain]].

Objectives: To describe 2 statistical methods for estimating trends in the incidence of heroin and cocaine use in Barcelona.

Methods: Admissions for treatment of heroin and cocaine consumption recorded by the Barcelona Drug Information System between 1991 and 2003 were used. We selected 4,367 subjects initiating treatment for the first time for heroin use, and 2,147 for cocaine use.