Chromoendoscopy Is Not Superior to White Light Endoscopy in Improving Adenoma Detection in Lynch Syndrome Cohort Undergoing Surveillance with High-Resolution Colonoscopy: A Real-World Evidence Study.

BACKGROUND: Endoscopic surveillance in patients with Lynch syndrome (LS) is crucial due to a genetically based high risk of colorectal cancer (CRC). We aimed to compare the adenoma detection rate (ADR) between high-resolution white light endoscopy (WLE) alone and WLE plus dye chromoendoscopy (CE) in a cohort of LS patients. METHODS: In a context of real-world data, we retrospectively enrolled 50 LS patients who had non-randomly undergone WLE versus CE surveillance examinations from 2007 to 2019. The 2 groups were compared at baseline (BL) in terms of the rate of patients with lesions and the number of lesions, and at follow-up (FU), to evaluate a possible enhanced detection rate. Longitudinal analysis of the effect of the endoscopy type on the main outcomes was performed by generalized linear mixed models. RESULTS: Forty-two patients had undergone at least one diagnostic colonoscopy. At BL and at FU analysis, we found no significant differences in detection rates and clinical-pathological features between WLE and CE groups. At the longitudinal analysis, an increase in the endoscopy rank (i.e., the position of each colonoscopy for all the colonoscopies that a patient had undergone) was associated with an increase in polyp detection rate (p = 0.006) and ADR (p = 0.005), while a trend toward significance (p = 0.069) was found for endoscopy type (CE vs. WLE) in the detection of serrated lesions. CONCLUSIONS: CE is not superior to high-resolution WLE in increasing the ADR. Even under standard WLE, an active and careful endoscopic surveillance of LS patients can prevent CRC.

A spatiotemporal analysis of NO 2 concentrations during the Italian 2020 COVID-19 lockdown.

When a new environmental policy or a specific intervention is taken in order to improve air quality, it is paramount to assess and quantify-in space and time-the effectiveness of the adopted strategy. The lockdown measures taken worldwide in 2020 to reduce the spread of the SARS-CoV-2 virus can be envisioned as a policy intervention with an indirect effect on air quality. In this paper we propose a statistical spatiotemporal model as a tool for intervention analysis, able to take into account the effect of weather and other confounding factor, as well as the spatial and temporal correlation existing in the data. In particular, we focus here on the 2019/2020 relative change in nitrogen dioxide (NO 2 ) concentrations in the north of Italy, for the period of March and April during which the lockdown measure was in force. We found that during March and April 2020 most of the studied area is characterized by negative relative changes (median values around - 25%), with the exception of the first week of March and the fourth week of April (median values around 5%). As these changes cannot be attributed to a weather effect, it is likely that they are a byproduct of the lockdown measures. There are two aspects of our research that are equally interesting. First, we provide a unique statistical perspective for calculating the relative change in the NO 2 by jointly modeling pollutant concentrations time series. Second, as an output we provide a collection of weekly continuous maps, describing the spatial pattern of the NO 2 2019/2020 relative changes.

Impact of SARS-CoV-2 Pandemic on Colorectal Cancer Screening Delay: Effect on Stage Shift and Increased Mortality.

BACKGROUND & AIMS: The SARS-CoV-2 pandemic had a sudden, dramatic impact on healthcare. In Italy, since the beginning of the pandemic, colorectal cancer (CRC) screening programs have been forcefully suspended. We aimed to evaluate whether screening procedure delays can affect the outcomes of CRC screening. METHODS: We built a procedural model considering delays in the time to colonoscopy and estimating the effect on mortality due to up-stage migration of patients. The number of expected CRC cases was computed by using the data of the Italian screened population. Estimates of the effects of delay to colonoscopy on CRC stage, and of stage on mortality were assessed by a meta-analytic approach. RESULTS: With a delay of 0-3 months, 74% of CRC is expected to be stage I-II, while with a delay of 4-6 months there would be a 2%-increase for stage I-II and a concomitant decrease for stage III-IV (P = .068). Compared to baseline (0-3 months), moderate (7-12 months) and long (> 12 months) delays would lead to a significant increase in advanced CRC (from 26% to 29% and 33%, respectively; P = .008 and P < .001, respectively). We estimated a significant increase in the total number of deaths (+12.0%) when moving from a 0-3-months to a >12-month delay (P = .005), and a significant change in mortality distribution by stage when comparing the baseline with the >12-months (P < .001). CONCLUSIONS: Screening delays beyond 4-6 months would significantly increase advanced CRC cases, and also mortality if lasting beyond 12 months. Our data highlight the need to reorganize efforts against high-impact diseases such as CRC, considering possible future waves of SARS-CoV-2 or other pandemics.

The Effect of Corona Virus Lockdown on Air Pollution: Evidence from the City of Brescia in Lombardia Region (Italy).

After the outbreak of Corona virus pandemic in Italy, the government has taken extraordinary measures, including a national lockdown, to prevent the spread of the infection. This extraordinary situation has led to a reduction in air pollution levels measured in the whole Po Valley, usually known as one of the most polluted areas in Europe in terms of particulate matter (PM) and nitrogen dioxide (NO 2 ) concentrations. The main aim of this paper is to evaluate the effectiveness of the lockdown on the air quality improvement. In particular, an interrupted time series modelling approach is employed to test if a significant change in the level and the trend of the pollutant time series has occurred after the lockdown measure. The case study regards the city of Brescia (Northern Italy) and focuses on the comparison of the period before (January 1st-March 7th, 2020) and after (March 8th-March 27th, 2020) the lockdown. By adjusting for meteorology and Sunday effect, the results show that a significant change in air quality occurring in the post intervention period was observed only for a single NO 2 station located in a heavy traffic zone. In particular, the estimate of the time series slope, i.e. the expected change in the concentration associated with a time unit increase, decreases from -0.25 to -1.67 after the lockdown. For the remaining stations, no significant change was found in the concentration time series when comparing the two periods. This confirms the complexity of air pollutant concentration dynamics for the considered area, which is not merely related to emission sources but depends also on other factors as, for example, (micro and macro) meteorological conditions and the chemical and physical processes in the atmosphere, which are all independent of the lockdown measure.

A framework for estimating and visualising excess mortality during the COVID-19 pandemic.

COVID-19 related deaths underestimate the pandemic burden on mortality because they suffer from completeness and accuracy issues. Excess mortality is a popular alternative, as it compares observed with expected deaths based on the assumption that the pandemic did not occur. Expected deaths had the pandemic not occurred depend on population trends, temperature, and spatio-temporal patterns. In addition to this, high geographical resolution is required to examine within country trends and the effectiveness of the different public health policies. In this tutorial, we propose a framework using R to estimate and visualise excess mortality at high geographical resolution. We show a case study estimating excess deaths during 2020 in Italy. The proposed framework is fast to implement and allows combining different models and presenting the results in any age, sex, spatial and temporal aggregation desired. This makes it particularly powerful and appealing for online monitoring of the pandemic burden and timely policy making.

Agrimonia: a dataset on livestock, meteorology and air quality in the Lombardy region, Italy.

The air in the Lombardy region, Italy, is one of the most polluted in Europe because of limited air circulation and high emission levels. There is a large scientific consensus that the agricultural sector has a significant impact on air quality. To support studies quantifying the role of the agricultural and livestock sectors on the Lombardy air quality, this paper presents a harmonised dataset containing daily values of air quality, weather, emissions, livestock, and land and soil use in the years 2016-2021, for the Lombardy region. The daily scale is obtained by averaging hourly data and interpolating other variables. In fact, the pollutant data come from the European Environmental Agency and the Lombardy Regional Environment Protection Agency, weather and emissions data from the European Copernicus programme, livestock data from the Italian zootechnical registry, and land and soil use data from the CORINE Land Cover project. The resulting dataset is designed to be used as is by those using air quality data for research.

Regional excess mortality during the 2020 COVID-19 pandemic in five European countries.

The impact of the COVID-19 pandemic on excess mortality from all causes in 2020 varied across and within European countries. Using data for 2015-2019, we applied Bayesian spatio-temporal models to quantify the expected weekly deaths at the regional level had the pandemic not occurred in England, Greece, Italy, Spain, and Switzerland. With around 30%, Madrid, Castile-La Mancha, Castile-Leon (Spain) and Lombardia (Italy) were the regions with the highest excess mortality. In England, Greece and Switzerland, the regions most affected were Outer London and the West Midlands (England), Eastern, Western and Central Macedonia (Greece), and Ticino (Switzerland), with 15-20% excess mortality in 2020. Our study highlights the importance of the large transportation hubs for establishing community transmission in the first stages of the pandemic. Here, we show that acting promptly to limit transmission around these hubs is essential to prevent spread to other regions and countries.

Changes in digestive cancer diagnosis during the SARS-CoV-2 pandemic in Italy: A nationwide survey.

BACKGROUND: The SARS-CoV-2 pandemic has had a huge impact on healthcare systems, resulting in many routine diagnostic procedures either being halted or postponed. AIMS: To evaluate whether the diagnoses of colorectal, gastric and pancreatic cancers have been impacted by the SARS-CoV-2 pandemic in Italy. METHODS: A survey designed to collect the number of histologically-proven diagnoses of the three cancers in gastroenterology services across Italy from January 1 to October 31 in 2017-2020. Non-parametric ANOVA for repeated measurements was applied to compare distributions by years and macro-areas. RESULTS: Compared to 2019, in 2020 gastric cancer diagnoses decreased by 15.9%, CRC by 11.9% and pancreatic by 9.9%. CRC distributions showed significant differences between all years, stomach cancer between 2018 and 2020 and 2019-2020, and pancreatic cancer only between 2017 and 2019. The 2019-2020 comparison showed fewer CRC diagnoses in the North (-13.7%), Center (-16.5%) and South (-4.1%), fewer stomach cancers in the North (-19.0%) and South (-9.4%), and fewer pancreatic cancers in the North (-14.1%) and Center (-4.7%), with an increase in the South (+12.3%). Distributions of CRC and gastric cancer were significantly different between all years in the North. CONCLUSIONS: This survey highlights the concerning effects of the COVID-19 pandemic on the diagnostic yield of gastroenterology services for stomach, colorectal and pancreatic cancers in Italy.

Estimating weekly excess mortality at sub-national level in Italy during the COVID-19 pandemic.

In this study we present the first comprehensive analysis of the spatio-temporal differences in excess mortality during the COVID-19 pandemic in Italy. We used a population-based design on all-cause mortality data, for the 7,904 Italian municipalities. We estimated sex-specific weekly mortality rates for each municipality, based on the first four months of 2016-2019, while adjusting for age, localised temporal trends and the effect of temperature. Then, we predicted all-cause weekly deaths and mortality rates at municipality level for the same period in 2020, based on the modelled spatio-temporal trends. Lombardia showed higher mortality rates than expected from the end of February, with 23,946 (23,013 to 24,786) total excess deaths. North-West and North-East regions showed one week lag, with higher mortality from the beginning of March and 6,942 (6,142 to 7,667) and 8,033 (7,061 to 9,044) total excess deaths respectively. We observed marked geographical differences also at municipality level. For males, the city of Bergamo (Lombardia) showed the largest percent excess, 88.9% (81.9% to 95.2%), at the peak of the pandemic. An excess of 84.2% (73.8% to 93.4%) was also estimated at the same time for males in the city of Pesaro (Central Italy), in stark contrast with the rest of the region, which does not show evidence of excess deaths. We provided a fully probabilistic analysis of excess mortality during the COVID-19 pandemic at sub-national level, suggesting a differential direct and indirect effect in space and time. Our model can be used to help policy-makers target measures locally to contain the burden on the health-care system as well as reducing social and economic consequences. Additionally, this framework can be used for real-time mortality surveillance, continuous monitoring of local temporal trends and to flag where and when mortality rates deviate from the expected range, which might suggest a second wave of the pandemic.

An analysis of temporal and spatial patterns in Italian hospitalization rates for multiple diagnosis.

In this paper, the Italian hospitalization database provided by the Ministry of Health is analyzed in terms of the temporal and spatial patterns of the hospitalization rates. The database covers the period 2010-2012 and the rates are evaluated for 110 Italian provinces and 18 diagnosis groups as defined by the ICD-9 classification. The analysis is based on a novel model-based clustering approach which enables clustering of spatially registered time series with respect to latent temporal patterns. The clustering result is analyzed to study the spatial distribution of the latent temporal patterns and their trend in order to identify possible critical areas in terms of increasing rates. Additionally, emerging spatial patterns may help common causes driving the hospitalization rates to be identified.

Two-stage Bayesian model to evaluate the effect of air pollution on chronic respiratory diseases using drug prescriptions.

Exposure to high levels of air pollutant concentration is known to be associated with respiratory problems which can translate into higher morbidity and mortality rates. The link between air pollution and population health has mainly been assessed considering air quality and hospitalisation or mortality data. However, this approach limits the analysis to individuals characterised by severe conditions. In this paper we evaluate the link between air pollution and respiratory diseases using general practice drug prescriptions for chronic respiratory diseases, which allow to draw conclusions based on the general population. We propose a two-stage statistical approach: in the first stage we specify a space-time model to estimate the monthly NO2 concentration integrating several data sources characterised by different spatio-temporal resolution; in the second stage we link the concentration to the ß2-agonists prescribed monthly by general practices in England and we model the prescription rates through a small area approach.

Spatial and spatio-temporal models with R-INLA.

During the last three decades, Bayesian methods have developed greatly in the field of epidemiology. Their main challenge focusses around computation, but the advent of Markov Chain Monte Carlo methods (MCMC) and in particular of the WinBUGS software has opened the doors of Bayesian modelling to the wide research community. However model complexity and database dimension still remain a constraint. Recently the use of Gaussian random fields has become increasingly popular in epidemiology as very often epidemiological data are characterised by a spatial and/or temporal structure which needs to be taken into account in the inferential process. The Integrated Nested Laplace Approximation (INLA) approach has been developed as a computationally efficient alternative to MCMC and the availability of an R package (R-INLA) allows researchers to easily apply this method. In this paper we review the INLA approach and present some applications on spatial and spatio-temporal data.

Spatial and spatio-temporal models with R-INLA.

During the last three decades, Bayesian methods have developed greatly in the field of epidemiology. Their main challenge focusses around computation, but the advent of Markov Chain Monte Carlo methods (MCMC) and in particular of the WinBUGS software has opened the doors of Bayesian modelling to the wide research community. However model complexity and database dimension still remain a constraint. Recently the use of Gaussian random fields has become increasingly popular in epidemiology as very often epidemiological data are characterised by a spatial and/or temporal structure which needs to be taken into account in the inferential process. The Integrated Nested Laplace Approximation (INLA) approach has been developed as a computationally efficient alternative to MCMC and the availability of an R package (R-INLA) allows researchers to easily apply this method. In this paper we review the INLA approach and present some applications on spatial and spatio-temporal data.