Treatment of young adults with colorectal cancer (CRC) represents an unmet clinical need, especially as diagnosis in this population might lead to the greatest loss of years of life. Since 1994, CRC ...incidence in individuals younger than 50 years has been increasing by 2% per year. The surge in CRC incidence in young adults is particularly alarming as the overall CRC frequency has been decreasing. Early‐onset CRC are characterized by a more advanced stage at diagnosis, poorer cell differentiation, higher prevalence of signet ring cell histology, and left colon‐sided location of the primary tumor. Among EO‐CRC, approximately 30% of patients are affected by tumors harboring mutations causing hereditary cancer predisposing syndromes, and 20% have familial CRC. Most notably, the remaining 50% of EO‐CRC patients have neither hereditary syndromes nor familial CRC, thus representing a formidable challenge for research. In this review article we summarize epidemiology, clinical and molecular features, heredity and outcome of treatments of EO‐CRC, and provide considerations for future perspectives.
The prevalence of hereditary syndromes, familial syndromes and neither hereditary or familial (‘terra incognita’) syndromes among early‐onset colorectal cancer in young individuals. Figures are derived from studies in the text.
In the winter of 2016-2017, the number of deaths recorded in the north-west Europe was significantly higher than that in previous years. This spike in mortality was attributed principally to an ...influenza epidemic, but the contribution of air pollution and cold temperature has not been investigated. Information on the combined effect of low temperatures, influenza epidemic, and air pollution on mortality is inadequate. The objective of this study was to estimate the excess mortality in the winter of 2016-2017 in the metropolitan area of Milan, and to evaluate the independent short-term effect of 3 risk factors: low temperatures, the influenza epidemic, and air pollution.
We used a case-crossover, time-stratified study design. Mortality data were collected on all people aged > 65 years who died of natural causes, due to respiratory diseases or cardiovascular diseases, between December 1, 2016 and February 15, 2017. Environmental data were extracted from the Regional Environmental Protection Agency. The National Surveillance Network provided data on influenza epidemic.
Among the 7590 natural deaths in people aged > 65 years, 965 (13%) were caused by respiratory conditions, and 2688 (35%) were caused by cardiovascular conditions. There were statistically significant associations between the minimum recorded temperature and deaths due to natural causes (OR = 0.966, 95% CI: 0.944-0.989), and cardiovascular conditions (OR = 0.961, 95% CI: 0.925-0.999). There were also statistically significant association between the influenza epidemic and deaths due to natural causes (OR = 1.198, 95% CI: 1.156-1.241), cardiovascular conditions (OR = 1.153, 95% CI: 1.088-1.223), and respiratory conditions (OR = 1.303, 95% CI: 1.166-1.456). High levels of PM10 (60 and 70 μg/m
) were associated with a statistically significant increase in natural and cause-specific mortality. There were statistically significant interactions between PM10 and influenza for cardiovascular-related mortality, and between influenza and temperature for deaths due to natural causes.
Excess of mortality in Milan during winter 2016-2017 was associated with influenza epidemic and concomitant environmental exposures, specifically, the combined effect of air pollution and low temperatures. Policies mitigating the effects of environmental risk factors should be implemented to prevent future excess mortality.
This paper aims to assess the presence of gender differences in medication use and mortality in a cohort of patients affected exclusively by hypertension, in 193 municipalities in the Lombardy Region ...(Northern Italy), including Milan's metropolitan area.
A retrospective cohort study was conducted (N = 232,507) querying administrative healthcare data and the Register of Causes of Death. Hypertensive patients (55.4% women; 44.6% men) in 2017 were identified; gender differences in medication use (treatment, 80% compliance) and deaths (from all causes and CVDs) were assessed at two-year follow-ups in logistic regression models adjusted for age class, census-based deprivation index, nationality, and pre-existing health conditions. Models stratified by age, deprivation index, and therapeutic compliance were also tested.
Overall, women had higher odds of being treated, but lower odds of therapeutic compliance, death from all causes, and death from CVDs. All the outcomes had clear sex differences across age classes, though not between different levels of deprivation. Comparing patients with medication adherence, women had lower odds of death from all causes than men (with a narrowing protective effect as age increased), while no gender differences emerged in non-compliant patients.
Among hypertensive patients, gender differences in medication consumption and mortality have been found, but the extent to which these are attributable to a female socio-cultural disadvantage is questionable. The findings reached, with marked age-dependent effects in the outcomes investigated, suggest a prominent role for innate sex differences in biological susceptibility to the disease, whereby women would take advantage of the protective effects of their innate physiological characteristics, especially prior to the beginning of menopause.
In February 2021, the spread of a new variant of SARS-CoV-2 in the Lombardy Region, Italy caused concerns about school-aged children as a source of contagion, leading local authorities to adopt an ...extraordinary school closure measure. This generated a debate about the usefulness of such an intervention in light of the trade-off between its related benefits and costs (e.g. delays in educational attainment, impact on children and families' psycho-physical well-being). This article analyses the epidemiological impact of the school closure intervention in the Milan metropolitan area. Data from the Agency for Health Protection of the Metropolitan City of Milan allowed analysing the trend of contagion in different age classes before and after the intervention, adopting an interrupted times series design, providing a quasi-experimental counterfactual scenario. Segmented Poisson regression models of daily incident cases were performed separately for the 3-11-year-old, the 12-19-year-old, and the 20+-year-old age groups, examining the change in the contagion curves after the intervention, adjusting for time-varying confounders. Kaplan-Meier survival curves and Cox regression were used to assess the equality of survival curves in the three age groups before and after the intervention. Net of time-varying confounders, the intervention produced a daily reduction of the risk of contagion by 4% in those aged 3-11 and 12-19 (IRR = 0·96) and by 3% in those aged 20 or more (IRR = 0·97). More importantly, there were differences in the temporal order of contagion decrease between the age groups, with the epidemic curve lowering first in the school-aged children directly affected by the intervention, and only subsequently in the adult population, which presumably indirectly benefitted from the reduction of contagion among children. Though it was not possible to completely discern the effect of school closures from concurrent policy measures, a substantial decrease in the contagion curves was clearly detected after the intervention. The extent to which the slowdown of infections counterbalanced the social costs of the policy remains unclear.
Social inequalities in health are known to be influenced by the socioeconomic status of the territory in which people live. In the context of the ongoing coronavirus disease 2019 (COVID-19) pandemic, ...this study is aimed at assessing the role of 5 area-level indicators in shaping the risk of contagion in the provinces of Milan and Lodi (Lombardy, Italy), namely: educational disadvantage, unemployment, housing crowding, mobility, and population density. The study area includes the municipalities at the origin of the first Italian epidemic outbreak. Data on COVID-19 patients from the Integrated Datawarehouse for COVID Analysis in Milan were used and matched with aggregate-level data from the National Institute of Statistics Italy (Istat). Multilevel logistic regression models were used to estimate the association between the census block-level predictors and COVID-19 infection, independently of age, sex, country of birth, and preexisting health conditions. All the variables were significantly associated with the outcome, with different effects before and after the lockdown and according to the province of residence. This suggests a pattern of socioeconomic inequalities in the outbreak, which should be taken into account in the eventuality of future epidemics to contain their spread and its related disparities.
Abstract
Background
Non-natural mortality in children and adolescents is a global public health problem that varies widely from country to country. Data on child and adolescent maltreatment are not ...readily available, and mortality due to violent causes is also underestimated.
Methods
Injury-related mortality rates (overall and by specific causes) from 2000 to 2018 in selected European countries were analysed to observe mortality patterns in children and adolescents using data from the Eurostat database. Age-standardized mortality rates per 100,000 person-years were calculated for each country.
Joinpoint
regression analysis with a significance level of 0.05 and 95% confidence intervals was performed for mortality trends.
Results
Children and adolescent mortality from non-natural causes decreased significantly in Europe from 10.48 around 2005 to 5.91 around 2015. The Eastern countries (Romania, Bulgaria, Poland, Slovakia, Czech Republic) had higher rates; while Spain, Denmark, Italy, and the United Kingdom had the lowest. Rates for European Country declined by 5.10% per year over the entire period. Larger downward trends were observed in Ireland, Spain and Portugal; smaller downward trends were observed for Eastern countries (Bulgaria, Czech Republic, Poland, Slovakia) and Finland. Among specific causes of death, the largest decreases were observed for accidental causes (-5.9%) and traffic accidents (-6.8%).
Conclusions
Mortality among children and adolescents due to non-natural causes has decreased significantly over the past two decades. Accidental events and transport accidents recorded the greatest decline in mortality rates, although there are still some European countries where the number of deaths among children and adolescents from non-natural causes is high. Social, cultural, and health-related reasons may explain the observed differences between countries.
ObjectivesThis study describes a new strategy to reduce the impact of COVID-19 on the elderly and other clinically vulnerable subjects, where general practitioners (GPs) play an active role in ...managing high-risk patients, reducing adverse health outcomes.DesignRetrospective cohort study.SettingPopulation-based study including subjects resident in the province of Milan and Lodi.Participants127 735 residents older than 70 years, with specific chronic conditions.InterventionsWe developed a predictive algorithm for overall mortality risk based on demographic and clinical characteristics. All residents older than 70 years were classified as being at low or high risk of death from COVID-19 infection according to the algorithm. The high-risk group was assigned to their GPs for telephone triage and consultation. The high-risk cohort was divided into two groups based on GP intervention: patients who were not contacted and patients who were contacted by their GPs.Outcome measuresOverall mortality, COVID-19 morbidity and hospitalisation.ResultsPatients with increased risk of death from COVID-19 were 127 735; 495 669 patients were not at high risk and were not included in the intervention. Out of the high-risk subjects, 79 110 were included but not contacted by their GPs, while 48 625 high-risk subjects were included and contacted. Overall mortality, morbidity and hospitalisation was higher in high-risk patients compared with low-risk populations. High-risk patients contacted by their GPs had a 50% risk reduction in COVID-19 mortality, and a 70% risk reduction in morbidity and hospitalisation for COVID-19 compared with non-contacted patients.ConclusionsThe study showed that, during the COVID-19 outbreak, involvement of GPs and changes in care management of high-risk groups produced a significant reduction in all adverse health outcomes.
The dataset includes 4488 patients diagnosed with lung cancer (ICD-O 33, C33-C34) between 2010–2012 and 2016–2018 in the territory of the Agency for Health Protection (ATS) of Milan, Italy, and ...selected from its population cancer registry on the basis of availability of the following information: performance status (PS), age, sex, and stage at diagnosis. The dataset includes also the following variables, extracted from the health databases of the ATS and linked to the variables derived from the cancer registry through deterministic record linkage on a unique key (tax code): Charlson comorbidity index, presence of chronic obstructive pulmonary disease, number of hospitalizations, outpatient visits, emergency accesses and prescribed drugs in the previous year, and dispensed durable medical equipment in the previous three years. The dataset was used to develop a logistic prediction model for PS, dichotomized as ‘poor’ (ECOG, 3–5) and ‘good’ (ECOG, 0–2), on the basis of all other variables in the dataset. The prediction model was developed on a 50% random subsample of the described dataset (development dataset, n = 2,244) and validated on the remaining half. The area under the curve (AUC) of the model in the development and validation samples were 0.76 and 0.73, respectively. The developed model was used to predict ‘good’ vs. ‘poor’ PS in a sample of patients with advanced lung cancer, from the same registry and years, for which the information was not available. Researchers using registry data, or electronic claims, to perform studies of oncologic therapy effectiveness for lung cancer could use the reported coefficients to predict PS value, dichotomized as ‘good’ or ‘poor’.
ObjectivesThe emergency department (ED) is one of the most critical areas in any hospital. Recently, many countries have seen a rise in the number of ED visits, with an increase in length of stay and ...a detrimental effect on quality of care. Being able to forecast future demands would be a valuable support for hospitals to prevent high demand, particularly in a system with limited resources where use of ED services for non-urgent visits is an important issue.DesignTime-series cohort study.SettingWe collected all ED visits between January 2014 and December 2019 in the five larger hospitals in Milan. To predict daily volumes, we used a regression model with autoregressive integrated moving average errors. Predictors included were day of the week and year-round seasonality, meteorological and environmental variables, information on influenza epidemics and festivities. Accuracy of prediction was evaluated with the mean absolute percentage error (MAPE).Primary outcome measuresDaily all-cause EDs visits.ResultsIn the study period, we observed 2 223 479 visits. ED visits were most likely to occur on weekends for children and on Mondays for adults and seniors. Results confirmed the role of meteorological and environmental variables and the presence of day of the week and year-round seasonality effects. We found high correlation between observed and predicted values with a MAPE globally smaller than 8.1%.ConclusionsResults were used to establish an ED warning system based on past observations and indicators of high demand. This is important in any health system that regularly faces scarcity of resources, and it is crucial in a system where use of ED services for non-urgent visits is still high.
To evaluate whether symptoms of inflammatory bowel disease (IBD), before diagnosis modify dietary habits, and to investigate the pre-illness diet in patients with recent IBD in comparison with an ...age-matched healthy control group.
Overall, 83 new cases of IBD (41 ulcerative colitis, 42 Crohn's disease) and 160 healthy controls were studied. Portions per week of 34 foods and beverages before onset of symptoms were recorded using a validated questionnaire. Duration of symptoms before IBD diagnosis, presence of specific symptoms and their impact on subjective changes in usual dietary habits were also recorded. The association between diet and IBD was investigated by multiple logistic regression and dietary patterns were assessed by factor analysis.
Changes in dietary habits, due to the presence of symptoms, were reported by 38.6% of patients and were not significantly related to specific symptoms, rather to long duration of symptoms, only in Crohn's disease patients. In IBD patients who did not change dietary habits, moderate and high consumption of margarine (OR = 11.8 and OR = 21.37) was associated with ulcerative colitis, whilst high consumption of red meat (OR = 7.8) and high intake of cheese were associated with Crohn's disease.
More than one third of IBD patients change dietary habits before diagnosis. Margarine, red meat and cheese increase the risk of ulcerative colitis and Crohn's disease.