Winning during a pandemic: epidemiology of SARS-CoV-2 during EURO2020 in Italy.

INTRODUCTION: EURO2020 generated a growing media and population interest across the month period, that peaked with large spontaneous celebrations across the country upon winning the tournament. METHODS: We retrospectively analysed data from the national surveillance system (indicator-based) and from event-based surveillance to assess how the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) changed in June-July 2021 and to describe cases and clusters linked with EURO2020. RESULTS: Widespread increases in transmission and case numbers, mainly among younger males, were documented in Italy, none were linked with stadium attendance. Vaccination coverage against SARS-CoV-2 was longer among cases linked to EURO2020 than among the general population. CONCLUSIONS: Transmission increased across the country, mainly due to gatherings outside the stadium, where, conversely, strict infection control measures were enforced. These informal 'side' gatherings were dispersed across the entire country and difficult to control. Targeted communication and control strategies to limit the impact of informal gatherings occurring outside official sites of mass gathering events should be further developed.

Publisher Correction to: Temporal dynamics in total excess mortality and COVID-19 deaths in Italian cities.

An amendment to this paper has been published and can be accessed via the original article.

Temporal dynamics in total excess mortality and COVID-19 deaths in Italian cities.

BACKGROUND: Standardized mortality surveillance data, capable of detecting variations in total mortality at population level and not only among the infected, provide an unbiased insight into the impact of epidemics, like COVID-19 (Coronavirus disease). We analysed the temporal trend in total excess mortality and deaths among positive cases of SARS-CoV-2 by geographical area (north and centre-south), age and sex, taking into account the deficit in mortality in previous months. METHODS: Data from the Italian rapid mortality surveillance system was used to quantify excess deaths during the epidemic, to estimate the mortality deficit during the previous months and to compare total excess mortality with deaths among positive cases of SARS-CoV-2. Data were stratified by geographical area (north vs centre and south), age and sex. RESULTS: COVID-19 had a greater impact in northern Italian cities among subjects aged 75-84 and 85+ years. COVID-19 deaths accounted for half of total excess mortality in both areas, with differences by age: almost all excess deaths were from COVID-19 among adults, while among the elderly only one third of the excess was coded as COVID-19. When taking into account the mortality deficit in the pre-pandemic period, different trends were observed by area: all excess mortality during COVID-19 was explained by deficit mortality in the centre and south, while only a 16% overlap was estimated in northern cities, with quotas decreasing by age, from 67% in the 15-64 years old to 1% only among subjects 85+ years old. CONCLUSIONS: An underestimation of COVID-19 deaths is particularly evident among the elderly. When quantifying the burden in mortality related to COVID-19, it is important to consider seasonal dynamics in mortality. Surveillance data provides an impartial indicator for monitoring the following phases of the epidemic, and may help in the evaluation of mitigation measures adopted.

Mortality impacts of the coronavirus disease (COVID-19) outbreak by sex and age: rapid mortality surveillance system, Italy, 1 February to 18 April 2020.

Data from the rapid mortality surveillance system in 19 major Italian cities were used to carry out a timely assessment of the health impact of the COVID-19 epidemic. By 18 April, a + 45% excess in mortality was observed, with a higher impact in the north of the country (+ 76%). The excess was greatest among men, with an increasing trend by age. Surveillance data can be used to evaluate the lockdown and re-opening phases.

[Temporal variations in excess mortality during phase 1 and phase 2 of the COVID-19 epidemic in Italy]. / Variazioni temporali della mortalità totale e nei decessi per COVID-19 durante la fase 1 e la fase 2 dell'epidemia in Italia.

OBJECTIVES: to assess the temporal variation in excess total mortality and the portion of excess explained by COVID-19 deaths by geographical area, gender, and age during the COVID-19 epidemic. DESIGN: descriptive analysis of temporal variations of total excess deaths and COVID-19 deaths in the phase 1 and phase 2 of the epidemic in Italy. SETTING AND PARTICIPANTS: 12 Northern cities and 20 Central-Southern cities from December 2019 to June 2020: daily mortality from the National Surveillance System of Daily Mortality (SiSMG) and COVID-19 deaths from the integrated COVID-19 surveillance system. MAIN OUTCOME MEASURES: total mortality excess and COVID-19 deaths, defined as deaths in microbiologically confirmed cases of SARS-CoV-2, by gender and age groups. RESULTS: the largest excess mortality was observed in the North and during the first phase of the epidemic. The portion of excess mortality explained by COVID-19 decreases with age, decreasing to 51% among the very old (>=85 years). In phase 2 (until June 2020), the impact was more contained and totally attributable to COVID-19 deaths and this suggests an effectiveness of social distancing measures. CONCLUSIONS: mortality surveillance is a sensible information basis for the monitoring of health impact of the different phases of the epidemic and supporting decision making at the local and national level on containment measures to put in place in coming months.

Screening for Infectious Diseases among Newly Arrived Migrants: Experiences and Practices in Non-EU Countries of the Mediterranean Basin and Black Sea.

Changing migration dynamics in the Mediterranean Sea and differences in infectious diseases (ID) burden between the countries of origin have raised questions whether public health actions are needed to avoid the transmission of ID. Screening newly arrived migrants for ID is one health monitoring option, offering opportunities for prevention, early detection and treatment. The authors conducted a survey among country experts in non-European Union countries of the Mediterranean and Black Sea, in order to explore current ID screening practices and policies for newly arrived migrants. The association between the existence of guidelines and the proportion of refugees in the population was also estimated. Eighteen country experts responded (90%) out of the 20 invited. Eleven countries (61%) implemented screening programmes and six (38%) had national guidelines. Screening was performed most often for tuberculosis at the holding level. A higher proportion of refugees in the population was associated with the existence of guidelines for screening (p = 0.05). Fourteen experts (88%) considered screening among migrants useful. The results show that screening for ID in newly arrived migrants is relevant for non-EU countries of the Mediterranean and Black Sea. Common guidelines could be promoted focusing on both individual and public health benefits of screening programmes.

A point-of-care test for facing the burden of undiagnosed celiac disease in the Mediterranean area: a pragmatic design study.

BACKGROUND: We aimed at assessing the factors that can influence results of the dissemination of an already validated, new generation commercial Point-of-Care Test (POCT) for detecting celiac disease (CD), in the Mediterranean area, when used in settings where it was designed to be administered, especially in countries with poor resources. METHODS: Pragmatic study design. Family pediatricians at their offices in Italy, nurses and pediatricians in Slovenia and Turkey at pediatricians', schools and university primary care centers looked for CD in 3,559 (1-14 yrs), 1,480 (14-23 yrs) and 771 (1-18 yrs) asymptomatic subjects, respectively. A new generation POCT detecting IgA-tissue antitransglutaminase antibodies and IgA deficiency in a finger-tip blood drop was used. Subjects who tested positive and those suspected of having CD were referred to a Celiac Centre to undergo further investigations in order to confirm CD diagnosis. POCT Positive Predictive Value (PPV) at tertiary care (with Negative Predictive Value) and in primary care settings, and POCT and CD rates per thousand in primary care were estimated. RESULTS: At tertiary care setting, PPV of the POCT and 95% CI were 89.5 (81.3-94.3) and 90 (56-98.5) with Negative Predictive Value 98.5 (94.2-99.6) and 98.7% (92-99.8) in children and adults, respectively. In primary care settings of different countries where POCT was performed by a different number of personnel, PPV ranged from 16 to 33% and the CD and POCT rates per thousand ranged from 4.77 to 1.3 and from 31.18 to 2.59, respectively. CONCLUSIONS: Interpretation of POCT results by different personnel may influence the performance of POC but dissemination of POCT is an urgent priority to be implemented among people of countries with limited resources, such as rural populations and school children.

Celiac disease in the Mediterranean area.

BACKGROUND: The World Gastroenterology Organization recommends developing national guidelines for the diagnosis of Celiac Disease (CD): hence a profile of the diagnosis of CD in each country is required. We aim to describe a cross-sectional picture of the clinical features and diagnostic facilities in 16 countries of the Mediterranean basin. Since a new ESPGHAN diagnostic protocol was recently published, our secondary aim is to estimate how many cases in the same area could be identified without a small intestinal biopsy. METHODS: By a stratified cross-sectional retrospective study design, we examined clinical, histological and laboratory data from 749 consecutive unselected CD children diagnosed by national referral centers. RESULTS: The vast majority of cases were diagnosed before the age of 10 (median: 5 years), affected by diarrhea, weight loss and food refusal, as expected. Only 59 cases (7.8%) did not suffer of major complaints. Tissue transglutaminase (tTG) assay was available, but one-third of centers reported financial constraints in the regular purchase of the assay kits. 252 cases (33.6%) showed tTG values over 10 times the local normal limit. Endomysial antibodies and HLA typing were routinely available in only half of the centers. CD was mainly diagnosed from small intestinal biopsy, available in all centers. Based on these data, only 154/749 cases (20.5%) would have qualified for a diagnosis of CD without a small intestinal biopsy, according to the new ESPGHAN protocol. CONCLUSIONS: This cross-sectional study of CD in the Mediterranean referral centers offers a puzzling picture of the capacities to deal with the emerging epidemic of CD in the area, giving a substantive support to the World Gastroenterology Organization guidelines.

Effect of lysine hyaluronate on the healing of decubitus ulcers in rehabilitation patients.

INTRODUCTION: Chronically hospitalized patients are often burdened with skin ulcerations, which may be persistent and even irreversible. Treatment with hyaluronic acid is widely used in the early phases of the ulcers to relieve symptoms and accelerate the healing process. The present study hypothesized that lysine hyaluronate (Lys-HA) (Lysial(®), Fatai-Nyl Srl; Jasper LLC, Lugano, Switzerland), a new formulation of hyaluronic acid, would improve the healing of decubitus ulcers more than the commonly used sodium hyaluronate (SH). A double-blind randomized controlled trial was designed to assess the superiority of Lys-HA versus SH on decubitus ulcer size reduction over a 15-day period, and on the time necessary to reach 50% lesion size regression. METHODS: After a clinical evaluation, 50 hospitalized patients with decubitus ulcers were divided into three groups according to ulcer stage (stage 1: erythema and edema; stage 2: all-thickness skin destruction; stage 3: destruction of subcutaneous tissue) and randomized to receive Lys-HA or SH. Digital photographs were taken before the start of treatment, then every 3 days, and at the end of the study. Pre- and posttreatment differences in each group were tested using Student t tests and analysis of covariance with basis values as covariates. RESULTS: Ulcer reduction was greater in all the Lys-HA groups than SH groups. In stage 1 patients, 90% and 70% lesion size reductions were observed in the groups allocated to Lys-HA and SH, respectively (P<0.05). In stage 2 patients, 70% and 40% lesion size reductions were observed in the Lys-HA and SH groups, respectively (P<0.02). In stage 3 patients, 71% and 29% lesion size reductions were observed in the Lys-HA and SH groups, respectively (P<0.01). The regression time of 50% of lesion size was shorter in all the Lys-HA groups than SH groups (P<0.05). CONCLUSION: The use of Lys-HA in the healing process of decubitus ulcers provides an improved efficacy with respect to SH in hospitalized patients, suggesting its use from the early phases of ulceration.

Natalizumab: a country-based surveillance program.

Natalizumab is a humanized monoclonal antibody with a selective adhesion-molecule inhibitor effect, and a demonstrated efficacy in decreasing the frequency of relapses and progression of disability in relapsing-remitting multiple sclerosis (RR MS). After the approval of FDA and EMEA in MS cases unresponsive to immunomodulating therapy or in severe MS patients also not previously treated with interferons, and considering the concern on the possible side effects, an accurate program of surveillance was organized in our country by a combined effort of AIFA, Cineca, Department of Pharmacology of University of Bologna, and a group of neurologists appointed by the National Society of Neurology (SIN). After 15 months from the authorization of natalizumab therapy in MS, as of 31 March 2008, 908 cases have been treated with natalizumab and enrolled in this pharmaco-vigilance study. The mean age is 35 years, while the duration of disease is longer and disability is higher than that reported in the registrative study. Side effects are at the moment mild and similar to those previously described. At follow-up, the majority of treated cases are stable or ameliorated. The treatment was discontinued in 6% of patients.

An update on the first decade of the European centralized procedure: how many innovative drugs?

AIMS: In a previous paper, we proposed an algorithm to assess the degree of therapeutic innovation of the agents approved by the European centralized procedure, which must be followed by biotechnological products and is optional for drugs claimed as innovative. A low overall degree of therapeutic innovation (about 30%) was found. This figure may be an underestimate of the actual level of innovation, because common biotechnological products, such as recombinant human insulins, must follow this procedure. To test the hypothesis that therapeutic innovation prevails among nonbiotechnological products, we evaluated separately the degree of therapeutic innovation of biotechnological vs. nonbiotechnological agents in the first decade of European Medicines Agency activity, also studying a possible time trend. METHODS: We assessed, for each drug: (i) the seriousness of the target disease, (ii) the availability of previous treatments, and (iii) the extent of therapeutic effect according to the previously proposed algorithm. RESULTS: Our analysis considered 251 medicinal products corresponding to 198 active substances, classified according to four main areas as therapeutic agents (88.9%), diagnostics (5.5%), vaccines (5.1%) and life-style drugs (0.5%). Among all therapeutic agents, 49 out of 176 agents (28%) were classified as having an important degree of therapeutic innovation. Fifteen out of 60 biotechnological therapeutic agents were considered important therapeutic innovations (25%), whereas this figure was 29% for nonbiotechnological agents. CONCLUSIONS: Among active substances claimed as innovative by the manufacturers, only a minority deserve this definition according to our algorithm.

Therapeutic innovation in the European Union: analysis of the drugs approved by the EMEA between 1995 and 2003.

Since January 1995, all European Union applications for marketing approval for medicinal products derived from biotechnology and other drugs considered potentially innovative follow the EMEA centralized procedure. In order to assess the overall degree of therapeutic innovation of these drugs, we considered, for each approved agent, its target, the availability of previous treatments and the extent of its therapeutic effect. The following scores for therapeutic innovation were assigned through a consensus process: 'A' (important), 'B' (moderate) and 'C' (modest). The overall degree of important/moderate therapeutic innovation was 47% of all therapeutic agents (32% important; 15% moderate). Most (80%) of the EMEA-approved therapeutic agents were for serious diseases. The remaining ones were for risk factors (7%) or nonserious diseases (13%).