Theory and performance of substitution models for estimating relative causal effects in nutritional epidemiology.

BACKGROUND: Estimating relative causal effects (i.e., "substitution effects") is a common aim of nutritional research. In observational data, this is usually attempted using 1 of 2 statistical modeling approaches: the leave-one-out model and the energy partition model. Despite their widespread use, there are concerns that neither approach is well understood in practice. OBJECTIVES: We aimed to explore and illustrate the theory and performance of the leave-one-out and energy partition models for estimating substitution effects in nutritional epidemiology. METHODS: Monte Carlo data simulations were used to illustrate the theory and performance of both the leave-one-out model and energy partition model, by considering 3 broad types of causal effect estimands: 1) direct substitutions of the exposure with a single component, 2) inadvertent substitutions of the exposure with several components, and 3) average relative causal effects of the exposure instead of all other dietary sources. Models containing macronutrients, foods measured in calories, and foods measured in grams were all examined. RESULTS: The leave-one-out and energy partition models both performed equally well when the target estimand involved substituting a single exposure with a single component, provided all variables were measured in the same units. Bias occurred when the substitution involved >1 substituting component. Leave-one-out models that examined foods in mass while adjusting for total energy intake evaluated obscure estimands. CONCLUSIONS: Regardless of the approach, substitution models need to be constructed from clearly defined causal effect estimands. Estimands involving a single exposure and a single substituting component are typically estimated more accurately than estimands involving more complex substitutions. The practice of examining foods measured in grams or portions while adjusting for total energy intake is likely to deliver obscure relative effect estimands with unclear interpretations

Estimating the effects of lockdown timing on COVID-19 cases and deaths in England: A counterfactual modelling study

Background: during the first wave of the COVID-19 pandemic, the United Kingdom experienced one of the highest per-capita death tolls worldwide. It is debated whether this may partly be explained by the relatively late initiation of voluntary social distancing and mandatory lockdown measures. In this study, we used simulations to estimate the number of cases and deaths that would have occurred in England by 1 June 2020 if these interventions had been implemented one or two weeks earlier, and the impact on the required duration of lockdown.Methods: using official reported data on the number of Pillar 1 lab-confirmed cases of COVID-19 and associated deaths occurring in England from 3 March to 1 June, we modelled: the natural (i.e. observed) growth of cases, and the counterfactual (i.e. hypothetical) growth of cases that would have occurred had measures been implemented one or two weeks earlier. Under each counterfactual condition, we estimated the expected number of deaths and the time required to reach the incidence observed under natural growth on 1 June.Results: introducing measures one week earlier would have reduced by 74% the number of confirmed COVID-19 cases in England by 1 June, resulting in approximately 21,000 fewer hospital deaths and 34,000 fewer total deaths; the required time spent in full lockdown could also have been halved, from 69 to 35 days. Acting two weeks earlier would have reduced cases by 93%, resulting in between 26,000 and 43,000 fewer deaths.Conclusions: our modelling supports the claim that the relatively late introduction of social distancing and lockdown measures likely increased the scale, severity, and duration of the first wave of COVID-19 in England. Our results highlight the importance of acting swiftly to minimise the spread of an infectious disease when case numbers are increasing exponentially

Sex, gender, and medicine

Mounting evidence shows that biological sex and gender impacts how our bodies and brains work. As our traditional scientific model, heavily influenced by misguided policies and ingrained cultures, is rooted in the belief that males and females are interchangeable outside of our reproductive zones, it’s time for a scientific reboot. Depending upon the context, our chromosomes, hormones, and life experiences effect our lives in ways which are both inconsequential and critically important. To practice up-to-date medicine and optimize our own resiliency, it’s important to understand and openly discuss these very real differences. This introductory chapter is designed as a “sex and gender boot camp” and will review basic definitions, explore clinical and professional examples of sex and gender differences, provide a template for framing differences, and share the author’s personal experiences in discovering this material and using it to become more resilient