concrete: Targeted Estimation of Survival and Competing Risks in Continuous Time

This article introduces the R package concrete, which implements a recently developed targeted maximum likelihood estimator (TMLE) for the cause-specific absolute risks of time-to-event outcomes measured in continuous time. Cross-validated Super Learner machine learning ensembles are used to estimate propensity scores and conditional cause-specific hazards, which are then targeted to produce robust and efficient plug-in estimates of the effects of static or dynamic interventions on a binary treatment given at baseline quantified as risk differences or risk ratios. Influence curve-based asymptotic inference is provided for TMLE estimates and simultaneous confidence bands can be computed for target estimands spanning multiple multiple times or events. In this paper we review the one-step continuous-time TMLE methodology as it is situated in an overarching causal inference workflow, describe its implementation, and demonstrate the use of the package on the PBC dataset.Comment: 18 pages, 4 figures, submitted to the R Journa

New drug candidates for depression - a nationwide population-based study

OBJECTIVE: To investigate whether continued use of non-aspirin NSAID, low-dose aspirin, high-dose aspirin, statins, allopurinol and angiotensin agents decreases the rate of incident depression using Danish nationwide population-based registers. METHODS: All persons in Denmark who purchased the exposure medications of interest between 1995 and 2015 and a random sample of 30% of the Danish population was included in the study. Two different outcome measures were included, (i) a diagnosis of depressive disorder at a psychiatric hospital as in-patient or out-patient and (ii) a combined measure of a diagnosis of depression or use of antidepressants. RESULTS: A total of 1 576 253 subjects were exposed to one of the six drugs of interest during the exposure period from 2005 to 2015. Continued use of low-dose aspirin, statins, allopurinol and angiotensin agents was associated with a decreased rate of incident depression according to both outcome measures. Continued uses of non-aspirin NSAIDs as well as high-dose aspirin were associated with an increased rate of incident depression. CONCLUSION: The findings support the potential of agents acting on inflammation and the stress response system in depression as well as the potential of population-based registers to systematically identify drugs with repurposing potential

Supplementary Material for: Leukocyte Profile in Peripheral Blood and Neutrophil-Lymphocyte Ratio in Hidradenitis Suppurativa: A Comparative Cross-Sectional Study of 462 Cases

<b><i>Background:</i></b> Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease. Increasing evidence suggests that HS involves dysfunctional immune responses in both the adaptive and the innate immune system. The recently proposed association of HS with metabolic syndrome may further add to the inflammatory state in HS. <b><i>Objective:</i></b> To investigate the status of inflammation and leukocyte profile in the peripheral blood of HS patients. <b><i>Materials and Methods:</i></b> Using a comparative cross-sectional study design, we investigated blood samples of high-sensitivity C-reactive protein (hs-CRP) and leukocyte profile in hospital-treated HS patients (HS-HOSP), self-reported population-based HS patients (HS-POP) and population controls. <b><i>Results:</i></b> Our study comprised 32 individuals in the HS-HOSP group, 430 in the HS-POP group, and 20,780 controls. The median hs-CRP for the HS-HOSP group was 5.1 mg/l (quartile range 2.6-8.2), 2.2 mg/l (1.0-4.3) for the HS-POP group and 1.3 mg/l (0.7-2.9) for the controls. An age-sex-adjusted analysis revealed a significantly higher hs-CRP for both HS groups compared to controls (p < 0.0001). When performing age-sex-adjusted analysis, both HS groups had significantly higher odds of leukocytosis when compared to controls with an odds ratio for the HS-HOSP group of 4.38 (95% CI = 2.18-8.80; p < 0.0001) and 1.95 (95% CI = 1.58-2.42; p < 0.0001) for the HS-POP group. The age-sex-adjusted leukocyte differential count yielded significantly higher neutrophil (p < 0.0001) and monocyte (p = 0.0014, p = 0.0004) levels in the HS groups compared with controls. <b><i>Conclusion:</i></b> The hs-CRP levels associated with HS appear to be intermediate (2.2-5.1 mg/l), implying systemic inflammation rather than infection. The peripheral blood leukocytosis in HS was dominated by neutrophils and monocytes

Modeling Uncertainty in Climate Change: A Multi-Model Comparison

The economics of climate change involves a vast array of uncertainties, complicating both the analysis and development of climate policy. This study presents the results of the first comprehensive study of uncertainty in climate change using multiple integrated assessment models. The study looks at model and parametric uncertainties for population, total factor productivity, and climate sensitivity. It estimates the pdfs of key output variables, including CO2 concentrations, temperature, damages, and the social cost of carbon (SCC). One key finding is that parametric uncertainty is more important than uncertainty in model structure. Our resulting pdfs also provide insights on tail events