Exploring the impact of mobility restrictions on the COVID-19 spreading through an agent-based approach.

Background: The recent health emergency caused by the COVID-19 pandemic forced people to change their mobility habits, with the reduction of non-essential travels and the promotion online activities. During the first phase of the emergency in 2020, governments considered several mobility restrictions to avoid the pandemic diffusion. However, it is difficult to quantify the actual effects of these restrictions on the virus spreading, especially due to the biased data available. Notwithstanding the big role of data analysis to understand the pandemic phenomenon, it is also important to have more general models capable of predicting the impact of different policy scenarios, including territorial parameters, independently from the available infection data. In this respect, this paper proposes an agent-based model to simulate the impact of mobility restrictions on the spreading of the COVID-19 at a large scale level, by considering different factors that can be attributed to the diffusion and lethality of the virus and population mobility patterns. Methods: The first step of the method includes a zonation of the study area, according to administrative boundaries. A risk index is calculated for each zone considering indicators which can influence the virus spreading and people lethality: mean winter temperature, housing concentration, healthcare density, population mobility, air pollution and the percentage of population over 60 years old. The agent-based model associates the risk index to the agents and determines their "status" ("susceptible", "infected", "isolated", "recovered" or "dead") by combining the risk index with the mean infection duration, using a SIR-based approach (i.e. susceptible-infective-removed). Results: The study is applied to Italy. Several scenarios based on different mobility restrictions have been simulated, including the one based on the official data (status quo). The main results show that characterizing zones with a risk index allows to adopt local policies with almost the same effectiveness as in the case of restrictions extended to the full study area; scenario simulations return an increase in terms of infected (+20%) and deaths (+25%) with respect to the status quo. These results underline the importance of finding a trade-off between socio-economic benefits and health impact. Conclusions: The reproducibility of the proposed methodology and its scalability allow to apply it to different contexts and at a different administrative level, from the urban scale to a national one. Moreover, the model is able to provide a decision-support tool for the design of strategic plans to contrast pandemics based on respiratory diseases.

Risk of venous and arterial thromboembolic events in women with advanced breast cancer treated with CDK 4/6 inhibitors: A systematic review and meta-analysis.

BACKGROUND: Cyclin-dependent kinase inhibitors (CDKIs) may increase the risk of thrombotic events of endocrine therapy (ET) in women with hormone-sensitive, HER2-negative advanced breast cancer (BC). Aim of our systematic review is the estimate of the risk of venous and arterial thromboembolism in women with advanced BC treated with CDKIs in phase III randomized controlled trials (RCTs). METHODS: Studies were identified by electronic search of MEDLINE, EMBASE and CENTRAL database until October 2021. Risk of bias was assessed according to Cochrane criteria. Differences in thrombotic outcomes among groups were expressed as pooled odds ratio (OR) and corresponding 95% confidence interval (CI), which were calculated using both a fixed-effects and a random-effects model. Statistical heterogeneity was evaluated using the I2 statistic. RESULTS: We included 7 phase III RCTs (4415 patients) for a total of 15 papers (7 were the first published paper and 8 the follow-up papers). Reporting of thrombotic events was at high risk of bias. Women with advanced BC treated with CDKIs and ET had a two to threefold increased risk of venous thromboembolic event (VTE) compared to ET plus placebo arm [OR 2.90 (95% CI 1.32, 6.37; I2 = 0%) in the main papers and OR 2.20 (95% CI 0.93, 5.20; I2 = 49%) in the follow-up papers]. Women with advanced BC treated with CDKIs and ET had a non-significant mild increased risk of arterial thromboembolic event compared to ET plus placebo arm [OR 1.22 (95% CI 0.47, 3.18 I2 = 0%)]. CONCLUSIONS: CDKIs in combination with endocrine therapy are associated with a two to threefold higher risk of VTE in comparison to endocrine therapy alone in women with advanced breast cancer, while the risk of arterial events is still to be defined.