Myocarditis and pericarditis following the Coronavirus Disease 2019 (COVID-19) mRNA vaccines administration have been reported, but their frequency is still uncertain in the younger population. This study investigated the association between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) mRNA vaccines, BNT162b2, and mRNA-1273 and myocarditis/pericarditis in the population of vaccinated persons aged 12 to 39 years in Italy. We conducted a self-controlled case series study (SCCS) using national data on COVID-19 vaccination linked to emergency care/hospital discharge databases. The outcome was the first diagnosis of myocarditis/pericarditis between 27 December 2020 and 30 September 2021. Exposure risk period (0 to 21 days from the vaccination day, subdivided in 3 equal intervals) for first and second dose was compared with baseline period. The SCCS model, adapted to event-dependent exposures, was fitted using unbiased estimating equations to estimate relative incidences (RIs) and excess of cases (EC) per 100,000 vaccinated by dose, age, sex, and vaccine product. Calendar period was included as time-varying confounder in the model. During the study period 2,861,809 persons aged 12 to 39 years received mRNA vaccines (2,405,759 BNT162b2; 456,050 mRNA-1273); 441 participants developed myocarditis/pericarditis (346 BNT162b2; 95 mRNA-1273). Within the 21-day risk interval, 114 myocarditis/pericarditis events occurred, the RI was 1.99 (1.30 to 3.05) after second dose of BNT162b2 and 2.22 (1.00 to 4.91) and 2.63 (1.21 to 5.71) after first and second dose of mRNA-1273. During the [0 to 7) days risk period, an increased risk of myocarditis/pericarditis was observed after first dose of mRNA-1273, with RI of 6.55 (2.73 to 15.72), and after second dose of BNT162b2 and mRNA-1273, with RIs of 3.39 (2.02 to 5.68) and 7.59 (3.26 to 17.65). The number of EC for second dose of mRNA-1273 was 5.5 per 100,000 vaccinated (3.0 to 7.9). The highest risk was observed in males, at [0 to 7) days after first and second dose of mRNA-1273 with RI of 12.28 (4.09 to 36.83) and RI of 11.91 (3.88 to 36.53); the number of EC after the second dose of mRNA-1273 was 8.8 (4.9 to 12.9). Among those aged 12 to 17 years, the RI was of 5.74 (1.52 to 21.72) after second dose of BNT162b2; for this age group, the number of events was insufficient for estimating RIs after mRNA-1273. Among those aged 18 to 29 years, the RIs were 7.58 (2.62 to 21.94) after first dose of mRNA-1273 and 4.02 (1.81 to 8.91) and 9.58 (3.32 to 27.58) after second dose of BNT162b2 and mRNA-1273; the numbers of EC were 3.4 (1.1 to 6.0) and 8.6 (4.4 to 12.6) after first and second dose of mRNA-1273. The main study limitations were that the outcome was not validated through review of clinical records, and there was an absence of information on the length of hospitalization and, thus, the severity of the outcome. This population-based study of about 3 millions of residents in Italy suggested that mRNA vaccines were associated with myocarditis/pericarditis in the population younger than 40 years. According to our results, increased risk of myocarditis/pericarditis was associated with the second dose of BNT162b2 and both doses of mRNA-1273. The highest risks were observed in males of 12 to 39 years and in males and females 18 to 29 years vaccinated with mRNA-1273. The public health implication of these findings should be considered in the light of the proven mRNA vaccine effectiveness in preventing serious COVID-19 disease and death. Pharmacovigilance reports and observational studies have suggested an increased risk of myocarditis/pericarditis following the Coronavirus Disease 2019 (COVID-19) mRNA vaccine administration in people younger than 40 years. More information on the safety of COVID-19 mRNA vaccines is needed to further explore the relationship between mRNA vaccines and myocarditis/pericarditis in this population. We conducted a multiregional self-controlled case series (SCCS) study in Italy between 27 December 2020 to 30 September 2021 to investigate the association between myocarditis/pericarditis and COVID-19 mRNA vaccines in the population aged 12 to 39 years (n = 2,861,809). We found 441 myocarditis/pericarditis cases, 114 of which occurred within the 21-day risk interval after vaccination. Within the 21-day risk interval, the relative incidence (RI) was 1.99 (95% confidence interval [CI] 1.30 to 3.05) after the second dose of BNT162b2 and 2.22 (1.00 to 4.91) and 2.63 (1.21 to 5.71) after the first and second doses of mRNA-1273, respectively. Within the 0 to 7-day risk interval, the RI was 6.55 (2.73 to 15.72) after first dose of mRNA-1273 and 3.39 (2.02 to 5.68) and 7.59 (3.26 to 17.65) after the second doses of BNT162b2 and mRNA-1273, respectively. The highest risk was seen in males, 0 to 7 days after the first and second dose of mRNA-1273 (RIs of 12.28 (4.09 to 36.83) and 11.91 (3.88 to 36.53), respectively). After the second dose of mRNA-1273 in males, the excess of cases (EC) was 8.8 (4.9 to 12.9) per 100,000 vaccinated individuals. Consistent with previous studies, the findings suggest that COVID-19 mRNA vaccines were associated with myocarditis/pericarditis in the population younger than 40 years. The results provide information that could be helpful for the continuous assessment of the postmarketing benefit/risk profile of the COVID-19 mRNA vaccines and should be considered within the context of the proven mRNA vaccine effectiveness in reducing COVID-19 morbidity and mortality.

Introduction: COVID-19 case fatality rate in hospitalized patients varies across countries and studies. Reliable estimates, specific for age, sex, and comorbidities, are needed to monitor the epidemic, to compare the outcome in different settings, and to correctly design trials for COVID-19 interventions. The aim of this study was to provide population-based survival curves of hospitalized COVID-19 patients. Materials and Methods: A cohort study was conducted in three areas of Northern Italy, heavily affected by SARS-CoV-2 infection (Lombardy and Veneto Regions, and Reggio Emilia province), using a loco-regional COVID-19 surveillance system, linked to hospital discharge databases. We included all patients testing positive for SARS-CoV-2 RNA by RT-PCR on nasopharyngeal/throat swab samples who were hospitalized from 21 February to 21 April 2020. Kaplan–Meier survival estimates were calculated at 14 and 30 days for death in any setting, stratifying by age, sex, and the Charlson Index. Results: Overall, 42,926 hospitalized COVID-19 patients were identified. Patients’ median age was 69 years (IQR: 57– 79), 62.6% were males, and 6.0% had a Charlson Index ≥ 3. Survival curves showed that 22.0% (95% CI 21.6– 22.4) of patients died within 14 days and 27.6% (95% CI 27.2– 28.1) within 30 days from hospitalization. Survival was higher in younger patients and in females. The negative impact of comorbidities on survival was more pronounced in younger age groups. Conclusion: The high fatality rate observed in the study (28% at 30 days) suggests that studies should focus on death as primary endpoint during a follow-up of at least one month.

Cervical cancer screening is uncommon, especially in low-income countries and among lower socioeconomic status people in high-income countries. The aims of this study were to examine the adherence of Sicilian women to Pap testing and to identify the determinants of this in a population with a secondary prevention attitude lower than high-income countries and the national average. A cross-sectional study called “Save Eva in Sicily” was conducted among all women aged 25–64 years, with a sample drawn by the list of general practitioners (GPs), using a proportional sampling scheme, stratified by age and resident population. The study outcome was performing a Pap test within the past three years. The association between the outcome and Pap test determinants was analyzed through a multivariable logistic regression. Among the 365 interviewed women, 66% (n = 243) had a Pap test during the last 3 years. On the other hand, 18% of the other women (n = 66) had performed at least one Pap test previously and 16% (n = 56) had never had a Pap test. In a multivariable model, GPs’ advice (adjusted OR 2.55; 95% CI 1.57–4.14) and perceived susceptibility (adjusted OR 3.24; 95% CI 1.92–5.48) increased the likelihood of the execution of a Pap test. The “Save Eva in Sicily” study identified GP advice and perceived cancer severity as the main correlates of Pap testing among Sicilian women, producing evidence regarding how policy makers can increase compliance. Interventions to increase Pap test adhesion should focus on stimulating GPs to identify patients who regularly do not undergo it and to recommend testing on a regular basis to their patients.

Qualitative and quantitative research investigating determinants of adherence to clinical guidelines (GLs) on surgical antibiotic prophylaxis (SAP) are scarce. We conducted a mixed-method study aimed at investigating barriers and at describing attitudes of healthcare professionals (HCPs) regarding SAP in three Italian children’s hospitals. The study comprised two sequential phases: 1) collection of qualitative data through focus groups; 2) conduction of a survey on HCPs attitudes towards SAP. Focus groups were carried out in each hospital with a theoretical convenience sample of 10–15 HCPs. Categorical analysis was conducted. Emerging categories and additional topics derived by literature search were used to develop the survey questionnaire, which included 13 questions expressed through a 4-point Likert scale. Members of surgical teams were invited by e-mail to fill in the questionnaire. We summed up the points assigned to each 4-point Likert scale response and calculated a cumulative score expressing overall concordance to expected HCPs attitudes on SAP. We conducted univariate and multivariate analysis to evaluate the relationship among characteristics of respondents and concordance with expected attitudes. The main categories identified in the qualitative phase included determinants of general adherence to GLs (e.g., relevance of clinical judgment), individual determinants (e.g., poor knowledge on hospital data) and organizational/structural determinants (e.g., patient flows). A total of 357 HCPs participated in the survey (response rate: 82.1%). Among respondents, 75% reported that SAP should be performed with first or second-generation cephalosporins, 44% that 2–3 days of antibiotic administration are useful as a precaution after surgery, 32% that SAP is needed for all surgical procedures. At multivariate analysis, professional category (physicians vs nurses; OR: 3.31; 95%CI: 1.88–5.82), and hospital (hospital 1 and 2 vs hospital 3; ORs: 2.79, 95%CI: 1.22–6.36; 2.40, 95%CI: 1.30–4.43, respectively) were significantly and independently associated with higher concordance with expected attitudes on SAP. Results from this study were useful to identify obstacles to appropriate SAP use in children. In our setting, findings support that a quality-improvement intervention should take into account local contexts, with development of hospital policies, education on SAP recommendations, and dissemination of data on adherence to recommendations.

The signal of an association between vaccination in the second year of life with a hexavalent vaccine and sudden unexpected deaths (SUD) in the two days following vaccination was reported in Germany in 2003. A study to establish whether the immunisation with hexavalent vaccines increased the short term risk of SUD in infants was conducted in Italy. The reference population comprises around 3 million infants vaccinated in Italy in the study period 1999–2004 (1.5 million received hexavalent vaccines). Events of SUD in infants aged 1–23 months were identified through the death certificates. Vaccination history was retrieved from immunisation registries. Association between immunisation and death was assessed adopting a case series design focusing on the risk periods 0–1, 0–7, and 0–14 days after immunisation. Among the 604 infants who died of SUD, 244 (40%) had received at least one vaccination. Four deaths occurred within two days from vaccination with the hexavalent vaccines (RR = 1.5; 95% CI 0.6 to 4.2). The RRs for the risk periods 0–7 and 0–14 were 2.0 (95% CI 1.2 to 3.5) and 1.5 (95% CI 0.9 to 2.4). The increased risk was limited to the first dose (RR = 2.2; 95% CI 1.1 to 4.4), whereas no increase was observed for the second and third doses combined. The RRs of SUD for any vaccines and any risk periods, even when greater than 1, were almost an order of magnitude lower than the estimates in Germany. The limited increase in RRs found in Italy appears confined to the first dose and may be partly explained by a residual uncontrolled confounding effect of age.