Modelling the effect of a border closure between Switzerland and Italy on the spatiotemporal spread of COVID-19 in Switzerland.

We present an approach to extend the endemic-epidemic (EE) modelling framework for the analysis of infectious disease data. In its spatiotemporal formulation, spatial dependencies have originally been captured by static neighbourhood matrices. These weight matrices are adjusted over time to reflect changes in spatial connectivity between geographical units. We illustrate this extension by modelling the spread of COVID-19 disease between Swiss and bordering Italian regions in the first wave of the COVID-19 pandemic. The spatial weights are adjusted with data describing the daily changes in population mobility patterns, and indicators of border closures describing the state of travel restrictions since the beginning of the pandemic. These time-dependent weights are used to fit an EE model to the region-stratified time series of new COVID-19 cases. We then adjust the weight matrices to reflect two counterfactual scenarios of border closures and draw counterfactual predictions based on these, to retrospectively assess the usefulness of border closures. Predictions based on a scenario where no closure of the Swiss-Italian border occurred increased the number of cumulative cases in Switzerland by a factor of 2.7 (10th to 90th percentile: 2.2 to 3.6) over the study period. Conversely, a closure of the Swiss-Italian border two weeks earlier than implemented would have resulted in only a 12% (8% to 18%) decrease in the number of cases and merely delayed the epidemic spread by a couple of weeks. Our study provides useful insight into modelling the effect of epidemic countermeasures on the spatiotemporal spread of COVID-19.

Assessing the effect of school closures on the spread of COVID-19 in Zurich.

The effect of school closure on the spread of COVID-19 has been discussed intensively in the literature and the news. To capture the interdependencies between children and adults, we consider daily age-stratified incidence data and contact patterns between age groups which change over time to reflect social distancing policy indicators. We fit a multivariate time-series endemic-epidemic model to such data from the Canton of Zurich, Switzerland and use the model to predict the age-specific incidence in a counterfactual approach (with and without school closures). The results indicate a 17% median increase of incidence in the youngest age group (0-14 year olds), whereas the relative increase in the other age groups drops to values between 2% and 3%. We argue that our approach is more informative to policy makers than summarising the effect of school closures with time-dependent effective reproduction numbers, which are difficult to estimate due to the sparsity of incidence counts within the relevant age groups.

A large remaining potential in lipid-lowering drug treatment in the type 2 diabetes population: A Danish nationwide cohort study.

AIM: To assess lipid-lowering drug (LLD) use patterns during 1996-2017 and examine lipid levels in relation to the use of LLDs and prevalent atherosclerotic cardiovascular disease (ASCVD). METHODS: Using a nationwide diabetes register, 404 389 individuals with type 2 diabetes living in Denmark during 1996-2017 were identified. Individuals were followed from 1 January 1996 or date of type 2 diabetes diagnosis until date of emigration, death or 1 January 2017. Redemptions of prescribed LLDs were ascertained from the nationwide Register of Medicinal Products Statistics. Data on lipid levels were sourced from the National Laboratory Database since 2010. LLD coverage was calculated at any given time based on the redeemed amount and dose. Trends in lipid levels were estimated using an additive mixed-effect model. Low-density lipoprotein cholesterol (LDL-C) goal attainment was assessed based on recommended targets by the 2011, 2016 and 2019 guidelines for management of dyslipidaemias. RESULTS: LLD use has decreased since 2012 and only 55% of those with type 2 diabetes were LLD users in 2017. A decline in levels of total cholesterol and LDL-C, and an increase in triglycerides, was observed during 2010-2017. Annual mean levels of LDL-C were lower among LLD users compared with non-users (in 2017: 1.84 vs. 2.57 mmol/L). A greater fraction of LLD users achieved the LDL-C goal of less than 1.8 mmol/L compared with non-users (in 2017: 51.7% and 19%, respectively). Among LLD users with prevalent ASCVD, 26.9% and 55% had, as recommended by current 2019 European guidelines, an LDL-C level of less than 1.4 mmol/L and less than 1.8 mmol/L, respectively, in 2017. CONCLUSIONS: LLD use and LDL-C levels are far from optimal in the Danish type 2 diabetes population and improvement in LLD use could reduce ASCVD events.

Serotonin and Neuropeptides in Blood From Episodic and Chronic Migraine and Cluster Headache Patients in Case-Control and Case-Crossover Settings: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of this systematic review and meta-analysis (SR-MA) was to identify signaling molecule profiles and blood-derived biomarkers in migraine and cluster headache (CH) patients. BACKGROUND: Currently no migraine and CH valid biomarkers are available. Blood tests based on biomarker profiles have been used to gather information about the nervous system. Such tests have not yet been established within the primary headache field. METHODS: Case-control and case-crossover studies investigating whole blood, plasma, and serum were identified worldwide. The qualitative synthesis focused on 9 signaling molecules (serotonin [5-HT], calcitonin gene-related peptide [CGRP], endothelin-1 [ET-1], neurokinin A, neurokinin B, neuropeptide Y, pituitary adenylate cyclase-activating peptide 38 [PACAP-38], substance P (SP), and vasoactive intestinal peptide) and the quantitative synthesis on 5-HT and CGRP (≥5 comparisons available). The meta-analysis was conducted using standard and 3-level random effect models. RESULTS: Fifty-four eligible studies were identified (87.0% migraine, 9.3% CH, 3.7% migraine, and CH), and 2768 headache patients and 1165 controls included. Comparable fluctuations of 5-HT, CGRP, ET-1, PACAP-38, and SP in blood were generally observed between migraine and CH. Significant findings were observed for some subgroups and strata, for example, higher interictal and ictal 5-HT venous blood levels (ratio of means = 1.32, 95% CI: 1.08; 1.61; ratio of means = 1.23, 95% CI: 1.01; 1.49) in episodic migraine with aura with a female-dominated case group, higher interictal CGRP blood levels in episodic migraine (ratio of means = 1.63, 95% CI: 1.18; 2.26), and chronic migraine (ratio of means = 1.89, 95% CI: 1.33; 2.68), and higher ictal CGRP blood levels (ratio of means = 1.35, 95% CI: 1.09; 1.68) in episodic migraine were observed. In most subgroups, the quantitative synthesis revealed a high degree of heterogeneity between studies in part explained by the blood sampling site, specimen source, blood specimen, and sex distribution. Other potential confounders were age, aura, study quality, menstrual cycle, and methodology (eg, storage temperature). CONCLUSIONS: Potential migraine and CH signaling molecule profiles and biomarkers were revealed. Nevertheless, the high degree of heterogeneity between studies impedes identification of valid biomarkers but allowed us to assess the presence of confounders. Consideration of the potential confounders identified in this SR-MA might be of importance in the experimental planning of future studies. This consideration could be incorporated through establishment of specific guidelines.

Methods for calculating credible intervals for ratios of beta distributions with application to relative risks of death during the second plague pandemic.

Employing historical records we are able to estimate the risk of premature death during the second plague pandemic, and identify the Black Death and pestis secunda epidemics. We show a novel method of calculating Bayesian credible intervals for a ratio of beta distributed random variables and use this to quantify uncertainty of relative risk estimates for these two epidemics which we consider in a 2 × 2 contingency table framework.

Heat and health in Antwerp under climate change: Projected impacts and implications for prevention.

BACKGROUND: Excessive summer heat is a serious environmental health problem in several European cities. Heat-related mortality and morbidity is likely to increase under climate change scenarios without adequate prevention based on locally relevant evidence. METHODS: We modelled the urban climate of Antwerp for the summer season during the period 1986-2015, and projected summer daily temperatures for two periods, one in the near (2026-2045) and one in the far future (2081-2100), under the Representative Concentration Pathway (RCP) 8.5. We then analysed the relationship between temperature and mortality, as well as with hospital admissions for the period 2009-2013, and estimated the projected mortality in the near future and far future periods under changing climate and population, assuming alternatively no acclimatization and acclimatization based on a constant threshold percentile temperature. RESULTS: During the sample period 2009-2013 we observed an increase in daily mortality from a maximum daily temperature of 26°C, or the 89th percentile of the maximum daily temperature series. The annual average heat-related mortality in this period was 13.4 persons (95% CI: 3.8-23.4). No effect of heat was observed in the case of hospital admissions due to cardiorespiratory causes. Under a no acclimatization scenario, annual average heat-related mortality is multiplied by a factor of 1.7 in the near future (24.1deaths/year CI 95%: 6.78-41.94) and by a factor of 4.5 in the far future (60.38deaths/year CI 95%: 17.00-105.11). Under a heat acclimatization scenario, mortality does not increase significantly in the near or in the far future. CONCLUSION: These results highlight the importance of a long-term perspective in the public health prevention of heat exposure, particularly in the context of a changing climate, and the calibration of existing prevention activities in light of locally relevant evidence.