Excess Total Mortality in Italy: An Update to February 2023 with Focus on Working Ages.

BACKGROUND: Italy had a persistent excess of total mortality up to July 2022. This study provides updated estimates of excess mortality in Italy until February 2023. METHODS: Mortality and population data from 2011 to 2019 were used to estimate the number of expected deaths during the pandemic. Expected deaths were obtained using over-dispersed Poisson regression models, fitted separately for men and women, including calendar year, age group, and a smoothed function of the day of the year as predictors. The excess deaths were then obtained by calculating the difference between observed and expected deaths and were computed at all ages and working ages (25-64 years). RESULTS: We estimated 26,647 excess deaths for all ages and 1248 for working ages from August to December 2022, resulting in a percent excess mortality of 10.2% and 4.7%, respectively. No excess mortality was detected in January and February 2023. CONCLUSIONS: Our study indicates substantial excess mortality beyond those directly attributed to COVID-19 during the BA.4 and BA.5 Omicron wave in the latter half of 2022. This excess could be attributed to additional factors, such as the heatwave during the summer of 2022 and the early onset of the influenza season.

Excess mortality in Italy in 2020 by sex and age groups accounting for demographic changes and temporal trends in mortality.

BACKGROUND: Differences between total deaths registered during the Covid-19 pandemic and those registered in a previous reference period is a valid measure of the pandemic effect. However, this does not consider demographic changes and temporal trends in mortality. OBJECTIVE: To estimate the excess mortality in 2020 in Italy considering demographic changes and temporal trends in mortality. METHODS: We used daily mortality and population data for the 2011-2019 period to estimate the expected deaths in 2020. Expected deaths were estimated, separately by sex, through an over-dispersed Poisson regression model including calendar year and age group as covariates, a smooth function of the year's week, and the logarithm of the population as offset. The difference between observed and expected deaths was considered a measure of excess mortality. RESULTS: In 2020, 746,146 deaths occurred in Italy. We estimated an excess mortality of 90,725 deaths (95% CI: 86,503-94,914), which became 99,289 deaths after excluding January and February, when mortality was lower than expected. The excess was higher among men (49,422 deaths) than women (41,303 deaths) and it was mostly detected at ages ≥80 (60,224 deaths) and ages 65-79 (25,791 deaths), while among the population aged 25-49 and 50-64 we estimated an excess of 281 and 4764 deaths, respectively. CONCLUSIONS: After considering demographic changes and temporal improvement in mortality the excess deaths in 2020 still remains above 90,000 deaths. More important, considering these factors, the excess at ages <80 years is revised upwards, while the excess at older ages is revised downwards.

Attributable Fraction of Cancer Related to Occupational Exposure in Italy.

BACKGROUND: Exposure to occupational carcinogens is an important and avoidable cause of cancer. We aimed to provide an evidence-based estimate of the burden of occupation-related cancers in Italy. METHODS: The attributable fraction (AF) was calculated based on the counterfactual scenario of no occupational exposure to carcinogens. We included exposures classified as IARC group 1 and with reliable evidence of exposure in Italy. Relative risk estimates for selected cancers and prevalences of exposure were derived from large-scale studies. Except for mesothelioma, a 15-20-year latency period between exposure and cancer was considered. The data on cancer incidence in 2020 and mortality in 2017 in Italy were obtained from the Italian Association of Cancer Registries. RESULTS: The most prevalent exposures were UV radiation (5.8%), diesel exhaust (4.3%), wood dust (2.3%) and silica dust (2.1%). Mesothelioma had the largest AF to occupational carcinogens (86.6%), followed by sinonasal cancer (11.8%) and lung cancer (3.8%). We estimated that 0.9% of cancer cases (N~3500) and 1.6% of cancer deaths (N~2800) were attributable to occupational carcinogens in Italy. Of these, about 60% were attributable to asbestos, 17.5% to diesel exhaust, followed by chromium and silica dust (7% and 5%). CONCLUSIONS: Our estimates provide up-to-date quantification of the low, but persistent, burden of occupational cancers in Italy.

Impact of the First and Second Lockdown for COVID-19 Pandemic on Preterm Birth, Low Birth Weight, Stillbirth, Mode of Labor, and of Delivery in Lombardy, Italy.

We investigated the effect of lockdown measures implemented in Lombardy on selected obstetric and perinatal outcomes. Births that occurred during the two lockdowns imposed (i.e., the first from 16 March to 2 June 2020 and the second from 3 November 2020 to 5 April 2021) and the comparison periods (i.e., the first from 16 March to 2 June 2018 and the second from 3 November 2018 to 5 April 2019) were identified using regional healthcare databases. The distribution of births according to the selected outcomes was computed and the Chi-square test was used for testing differences in the periods compared. During the two lockdowns, we observed a lower proportion of low birth weight, from 6.8% in the comparison period to 6.1% in the first lockdown (p = 0.019), and from 6.5% to 6.1% in the second one (p = 0.109). The proportion of preterm births decreased from 6.8% to 6.3% in the first lockdown (p = 0.097), and from 6.2% to 6.0% in the second one (p = 0.172). No differences in stillbirth rate emerged for both lockdowns. Induction of labor was more frequent during both lockdowns, from 28.6% to 32.7% in the first (p < 0.0001), and from 29.9% to 33.2% in the second one (p < 0.0001). Cesarean section was less frequent during the second lockdown.

Total Antioxidant Capacity and Total Oxidant Status and Disease Severity in a Cohort Study of COVID-19 Patients.

BACKGROUND: Previous reports have suggested the role of oxidative stress in progression of COVID-19 infection, but there is limited information regarding the effect of antioxidant capacity and total oxidant status of patients with COVID-19 on disease severity. In the present study, we aimed to investigate the relationship between total antioxidant capacity (TAC), total oxidant status (TOS), TAC/TOS levels, and disease severity in hospitalized patients with COVID-19. METHODS: This cohort study was carried out at Masih Daneshvari Hospital in Tehran, Iran, from September 2020 to October 2020. Clinical data of 331 patients with COVID-19 admitted to the hospital were analyzed and divided into mild, moderate, and severe groups (needed oxygen, intubation, and mechanical ventilation). The patients' TAC, TOS, and TAC/TOS levels were assessed using the serum samples by colorimetric assay kit. RESULTS: We found no significant difference in serum levels of TAC, TOS, and TAC/TOS in terms of the disease severity. CONCLUSIONS: These results indicated that total antioxidant capacity and total oxidant status may not be the determining factor on the disease severity.

European Groundshot-addressing Europe's cancer research challenges: a Lancet Oncology Commission.

Cancer research is a crucial pillar for countries to deliver more affordable, higher quality, and more equitable cancer care. Patients treated in research-active hospitals have better outcomes than patients who are not treated in these settings. However, cancer in Europe is at a crossroads. Cancer was already a leading cause of premature death before the COVID-19 pandemic, and the disastrous effects of the pandemic on early diagnosis and treatment will probably set back cancer outcomes in Europe by almost a decade. Recognising the pivotal importance of research not just to mitigate the pandemic today, but to build better European cancer services and systems for patients tomorrow, the Lancet Oncology European Groundshot Commission on cancer research brings together a wide range of experts, together with detailed new data on cancer research activity across Europe during the past 12 years. We have deployed this knowledge to help inform Europe's Beating Cancer Plan and the EU Cancer Mission, and to set out an evidence-driven, patient-centred cancer research roadmap for Europe. The high-resolution cancer research data we have generated show current activities, captured through different metrics, including by region, disease burden, research domain, and effect on outcomes. We have also included granular data on research collaboration, gender of researchers, and research funding. The inclusion of granular data has facilitated the identification of areas that are perhaps overemphasised in current cancer research in Europe, while also highlighting domains that are underserved. Our detailed data emphasise the need for more information-driven and data-driven cancer research strategies and planning going forward. A particular focus must be on central and eastern Europe, because our findings emphasise the widening gap in cancer research activity, and capacity and outcomes, compared with the rest of Europe. Citizens and patients, no matter where they are, must benefit from advances in cancer research. This Commission also highlights that the narrow focus on discovery science and biopharmaceutical research in Europe needs to be widened to include such areas as prevention and early diagnosis; treatment modalities such as radiotherapy and surgery; and a larger concentration on developing a research and innovation strategy for the 20 million Europeans living beyond a cancer diagnosis. Our data highlight the important role of comprehensive cancer centres in driving the European cancer research agenda. Crucial to a functioning cancer research strategy and its translation into patient benefit is the need for a greater emphasis on health policy and systems research, including implementation science, so that the innovative technological outputs from cancer research have a clear pathway to delivery. This European cancer research Commission has identified 12 key recommendations within a call to action to reimagine cancer research and its implementation in Europe. We hope this call to action will help to achieve our ambitious 70:35 target: 70% average survival for all European cancer patients by 2035.

Updated estimates of excess total mortality in Italy during the circulation of the BA.2 and BA.4-5 Omicron variants: April-July 2022.

BACKGROUND: The impact of new lineages and sub-lineages of Omicron on total and excess mortality is largely unknown. This study aims to provide estimates of excess mortality during the circulation of the Omicron variant in Italy updated to July 2022. METHODS: Over-dispersed Poisson regression models, fitted separately for men and women, on 2011-2019 mortality data were used to estimate the expected number of deaths during the Covid-19 pandemic. The excess deaths were then obtained by the difference between observed and expected deaths and computed at all ages and at working ages (25-64 years). RESULTS: Between April and June 2022, we estimated 9,631 excess deaths (+6.3%) at all ages (4,400 in April, 3,369 in May, 1,862 in June) and 12,090 in July 2022 (+23.4%). At working ages, the excess was 763 (+4.9%) in April-June 2022 and 679 (+13.0%) in July 2022. CONCLUSIONS: Excess total mortality persisted during the circulation of different lineages and sub-lineages of the Omicron variant in Italy. This excess was not limited to the elderly population but involved also working age individuals, though the absolute number of deaths was small. The substantial excess found in July 2022 is, however, largely attributable to high temperatures. At the end of the year, this may translate into 30 to 35,000 excess deaths, i.e. over 5% excess mortality. This reversed the long-term trend toward increasing life expectancy, with the relative implications in social security and retirement schemes.

No excess mortality among working-age Italians during the Omicron wave of Covid-19.

BACKGROUND: This study provides updated estimates of the excess deaths in Italy with a focus on the working-age population. METHODS: Over-dispersed Poisson regression models, fitted on 2011-2019 mortality data, and including terms for age, calendar year and a smooth function of the week of the year, were used to estimate the expected number of deaths during the Covid-19 pandemic. The excess deaths were then obtained by the difference between observed and expected deaths and reported according to the pandemic periods defined by the predominant circulating variant of SARS-CoV-2. RESULTS: Around 170,700 excess deaths at all ages were estimated between March 2020 and March 2022 in Italy with most of the excess occurring during the pre-Delta and Delta period, and 2930 excess deaths (+2.5%) during the Omicron wave. The excesses among the working age population were: 10,425 deaths (+11.8%) during the pre-Delta period, 2460 (+9.4%) during the Delta wave, 283 (+2.2%) during the transition period to Delta. Mortality was lower than expected during the Omicron wave (-6.1%). CONCLUSIONS: Over the periods preceding the Omicron wave, Covid-19 caused around 12,800 excess deaths among individuals of working age, accounting for over 10% excess death. This excess was no longer observed during the Omicron wave.

SARS-CoV-2 Circulation in the School Setting: A Systematic Review and Meta-Analysis.

The contribution of children to viral spread in schools is still debated. We conducted a systematic review and meta-analysis of studies to investigate SARS-CoV-2 transmission in the school setting. Literature searches on 15 May 2021 yielded a total of 1088 publications, including screening, contact tracing, and seroprevalence studies. MOOSE guidelines were followed, and data were analyzed using random-effects models. From screening studies involving more than 120,000 subjects, we estimated 0.31% (95% confidence interval (CI) 0.05-0.81) SARS-CoV-2 point prevalence in schools. Contact tracing studies, involving a total of 112,622 contacts of children and adults, showed that onward viral transmission was limited (2.54%, 95% CI 0.76-5.31). Young index cases were found to be 74% significantly less likely than adults to favor viral spread (odds ratio (OR) 0.26, 95% CI 0.11-0.63) and less susceptible to infection (OR 0.60; 95% CI 0.25-1.47). Lastly, from seroprevalence studies, with a total of 17,879 subjects involved, we estimated that children were 43% significantly less likely than adults to test positive for antibodies (OR 0.57, 95% CI 0.49-0.68). These findings may not applied to the Omicron phase, we further planned a randomized controlled trial to verify these results.

Excess total mortality during the Covid-19 pandemic in Italy: updated estimates indicate persistent excess in recent months.

BACKGROUND: New releases of daily mortality data are available in Italy; the last containing data up to 31 January 2022. This study revises previous estimates of the excess mortality in Italy during the Covid-19 pandemic. METHODS: Excess mortality was estimated as the difference between the number of registered deaths and the expected deaths. Expected deaths in March-December 2020, January-December 2021 and January 2022 were estimated separately by sex, through an over-dispersed Poisson regression model using mortality and population data for the period 2011-2019. The models included terms for calendar year, age group, a smooth function of week of the year and the natural logarithm of the population as offset term. RESULTS: We estimated 99,334 excess deaths (+18.8%) between March and December 2020, 61,808 deaths (+9.5%) in 2021 and 4143 deaths (+6.1%) in January 2022. Over the whole pandemic period, 13,039 excess deaths (+10.2%) were estimated in the age group 25-64 years with most of the excess observed among men [10,025 deaths (+12.6%) among men and 3014 deaths (+6.3%) among women]. CONCLUSIONS: Up to 31 January 2022, over 165 thousand excess deaths were estimated in Italy, of these about 8% occurred among the working age population. Despite high vaccination uptake, excess mortality is still observed in recent months.

Attitudes towards COVID-19 vaccination and containment measures in Italy and the role of occupational physicians.

BACKGROUND: Vaccine hesitancy is the main barrier to the effective management of COVID-19. This study aims to evaluate attitudes towards vaccination and containment measures in Italy, and the role of occupational physicians in the management of COVID-19. METHODS: Between 26 and 31 January 2022, we conducted a national online survey including 1000 respondents (631 workers) representative of the Italian population. A series of questions were asked to get information on attitudes towards COVID-19 vaccination, containment measures and management of COVID-19. Sampling weights were used to obtain national estimates. RESULTS: The majority of respondents (92.6%) received at least two doses of SARS-CoV-2 vaccine (or one dose of Janssen, Ad26.COV2.S), only 4.9% did not get any dose. Most interviewees (79.2%) stated that the decision to be vaccinated was their own choice, while only 4.3% were convinced by the general practitioner or the occupational physician. History of SARS-CoV-2 infection was reported by 23.9% of the participants (30.2% among workers); and 40% of the infected workers were contacted/visited by an occupational physician. CONCLUSIONS: Vaccine uptake was remarkably high in Italy. Occupational physicians played a relevant role in the management of COVID-19 in occupational settings.

Excess total mortality in 2021 in Italy was about one third of that observed in 2020.

BACKGROUND: Italy was severely hit by the Covid-19 pandemic with an excess of around 90,000 total deaths in 2020. Comparable data in 2021 are needed for monitoring the effects of the interventions adopted to control its spread and reduce the burden. This study estimates the excess mortality in Italy in the first eight months of 2021, with a focus on the working age population. METHODS: Excess mortality was estimated as difference between the number of registered deaths and the expected deaths. Expected deaths in March-December 2020 and January-August 2021 were estimated separately by sex, through an over-dispersed Poisson regression model using mortality and population data for the period 2011-2019 (before the Covid-19 outbreak). The models included terms for calendar year, age group, a smooth function of week of the year and the natural logarithm of the population as offset term.  Results: In the first eight months of 2021, we estimated 34,599 excess deaths (+7.9% of the expected deaths), of these 3667 were among individuals of working age (25-64 years). In this age group, mortality was 8.2% higher than expected with higher excesses among men (2972 deaths, +10.7%) than women (695 deaths, +4.1%). CONCLUSIONS: The excess deaths in the first eight months of 2021 account for about one third of that registered in 2020. Current data indicate that around 5000 excess deaths are expected by the end of the year, leading to a total excess for 2021 of around 40 thousand deaths. Despite the absence of influenza in January-March 2021, a relevant excess was also observed among the working age population.

Changes in Lifestyle and Dietary Habits during COVID-19 Lockdown in Italy: Results of an Online Survey.

COVID-19 is an unprecedented global pandemic. On 12 March 2020, a lockdown order was issued in Italy in attempt to contain the health crisis. The study aimed to assess the impact of the COVID-19 lockdown on diet, physical activity, sleep quality, and distress in an Italian cohort. An online anonymous interview, which included validated questionnaires was created to compare lifestyle habits pre- and during the lockdown. Data analysis from 604 subjects with a mean age of 29.8 years was carried out using multivariate analysis. Compared to pre-COVID-19 times, 67% of people changed their eating habits and increased consumption of foods containing added sugars. Women and men with low adherence to the Mediterranean Diet (MedDiet) were more likely to be physically inactive (p < 0.0001 and p < 0.01, respectively). Results from logistic regression showed a three times higher risk of being inactive if adherence to the MedDiet was low (p < 0.0001), especially in men between 26 and 35 years. Lower levels of distress were reported in males who were physically active (89%) (p < 0.001). Our findings may help to identify effective lifestyle interventions during restrictive conditions.

A survey on the frequency of COVID-19-like symptoms on students and staff of the University of Milan.

A survey was conducted through a web link on the students and staff of the Università degli Studi di Milano, Italy in the period 14-30 April 2020. It was anonymous at the source and included history of COVID-19-related questions (fever, headache, cold, cough, anosmia, gastrointestinal complaints and separately fever over 38.5°C) in the previous three weeks, and similar information on cohabitants. A total of 14 374 subjects were included. Overall, from 24 March to 30 April, 3138 subjects (21.8%) reported COVID-19-like symptoms, and 219 (1.5%) fever above 38.5°C; 217 subjects performed at least one swab. Of these, 46 were positive (21.3% of those performed, 0.3% of the total). The frequency of any symptom was similar in women and men, but fever above 38.5°C was lower in women (multivariate odds ratio (OR) = 0.65, 95% confidence interval, CI, 0.49-0.85). There was a strong association between symptoms in the respondent and in cohabitants: 64% of subjects with symptoms reported at least one cohabitant with symptoms, compared to 14% of asymptomatic subjects (OR = 11.4, 95% CI, 10.4-12.6). The lower risk of serious symptoms in women, and the strong intra-nucleus of cohabitation contagiousness are an indication that at least part of the symptoms was caused by a new pathogen - SARS-CoV-2. These data, therefore, suggest that the number of persons affected by COVID-19 was much greater in northern Italy than the number of recorded cases. This has implications for the prevention, management and mortality of other serious diseases, including cancer.

Area-level indicators of income and total mortality during the COVID-19 pandemic.

BACKGROUND: There is mounting evidence that socioeconomic inequalities in mortality have widened during the COVID-19 pandemic. This study aimed at evaluating the relationship between area-level indicators of income and total mortality during the first phase of COVID-19 pandemic in the most hit Italian region. METHODS: We conducted an ecological study based on the number of deaths registered in the municipalities of the Lombardy region (Italy) between January 2019 and June 2020. Municipalities were grouped according to quintiles of average income and pension of their resident population. Monthly age-standardized mortality ratios (MRs) between the poorest and the richest municipalities and the corresponding 95% CI were computed to evaluate whether the pre-existing socioeconomic inequalities widened during the pandemic. RESULTS: Over the study period, 175 853 deaths were registered. During the pre-pandemic period (January 2019 to February 2020) the MR between the poorest and the richest municipalities ranged between 1.12 (95% CI: 1.00-1.25) and 1.33 (95% CI: 1.20-1.47). In March 2020, when the pandemic began to rapidly spread in the region, it raised up to 1.61 (95% CI: 1.51-1.72) and decreased thereafter, reaching the pre-pandemic values in April 2020. Similar results were observed in the analysis of the mortality at ages 65 and over in municipalities grouped according to average pension, where the MR increased up to 1.82 (95% CI: 1.70-1.94) in March 2020. CONCLUSIONS: The socioeconomic inequalities in mortality widened in Lombardy, the Italian region most severely hit during the first phase of the COVID-19 pandemic.

Bergamo and Covid-19: How the Dark Can Turn to Light.

The novel coronavirus, SARS-CoV-2, continues to spread rapidly. Here we discuss the dramatic situation created by COVID-19 in Italy, particularly in the province of Bergamo (the most severely affected in the first wave), as an example of how, in the face of an unprecedented tragedy, acting (albeit belatedly)-including imposing a very strict lockdown-can largely resolve the situation within approximately 2 months. The measures taken here ensured that Bergamo hospital, which was confronted with rapidly rising numbers of severely ill COVID-19 patients requiring hospitalization, was able to meet the initial challenges of the pandemic. We also report that local organization and, more important, the large natural immunity against SARS-CoV-2 of the Bergamo population developed during the first wave of the epidemic, can explain the limited number of new COVID-19 cases during the more recent second wave compared to the numbers in other areas of Lombardy. Furthermore, we highlight the importance of coordinating the easing of containment measures to avoid what is currently observed in other countries, especially in the United States, Latin American and India, where this approach has not been adopted, and a dramatic resurgence of COVID-19 cases and an increase in the number of hospitalisations and deaths have been reported.

Prevalence of COVID-19-like symptoms in Italy and Lombardy, March-April 2020, and their implications on cancer prevention, diagnosis and management.

Two population-based surveys on coronavirus disease-2019 (Covid-19)-like symptoms were conducted by BVA-Doxa on representative samples of the general population from Italy and its largest region, Lombardy, with over 10 million inhabitants and heavily struck by Covid-19, on 27-30 March and 3-7 April, on a total of 2000 individuals - 353 from Lombardy. Overall, 14.2% of Italians - and 19.6% in Lombardy - reported Covid-19-like symptoms. The estimated prevalence was higher in the young, in smokers, and in Lombardy over the period 20 March to 7 April. Although the influenza season was ended by mid-March, at least part of the symptoms may be not Covid-19 related. Even assuming that only half are, at least 7% of Italians and 10% in Lombardy had been affected by Covid-19. To these, asymptomatic or paucisymptomatic cases have to be added. These estimates are at least one or two orders of magnitude larger than official registered cases. This has major implications for cancer prevention, management and treatment.