A NLP-based semi-automatic identification system for delays in follow-up examinations: an Italian case study on clinical referrals.

BACKGROUND: This study aims to propose a semi-automatic method for monitoring the waiting times of follow-up examinations within the National Health System (NHS) in Italy, which is currently not possible to due the absence of the necessary structured information in the official databases. METHODS: A Natural Language Processing (NLP) based pipeline has been developed to extract the waiting time information from the text of referrals for follow-up examinations in the Lombardy Region. A manually annotated dataset of 10 000 referrals has been used to develop the pipeline and another manually annotated dataset of 10 000 referrals has been used to test its performance. Subsequently, the pipeline has been used to analyze all 12 million referrals prescribed in 2021 and performed by May 2022 in the Lombardy Region. RESULTS: The NLP-based pipeline exhibited high precision (0.999) and recall (0.973) in identifying waiting time information from referrals' texts, with high accuracy in normalization (0.948-0.998). The overall reporting of timing indications in referrals' texts for follow-up examinations was low (2%), showing notable variations across medical disciplines and types of prescribing physicians. Among the referrals reporting waiting times, 16% experienced delays (average delay = 19 days, standard deviation = 34 days), with significant differences observed across medical disciplines and geographical areas. CONCLUSIONS: The use of NLP proved to be a valuable tool for assessing waiting times in follow-up examinations, which are particularly critical for the NHS due to the significant impact of chronic diseases, where follow-up exams are pivotal. Health authorities can exploit this tool to monitor the quality of NHS services and optimize resource allocation.

Impact of chronic GLP-1 RA and SGLT-2I therapy on in-hospital outcome of diabetic patients with acute myocardial infarction.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium glucose cotransporter-2 inhibitors (SGLT-2i) demonstrated cardiovascular and renal protection. Whether their benefits occur also during hospitalization for acute myocardial infarction (AMI) in patients with diabetes mellitus (DM) is not known. We evaluated in-hospital outcomes of patients hospitalized with AMI according to their chronic use of GLP-1 RA and/or SGLT-2i. METHODS: Using the health administrative databases of Lombardy, patients hospitalized with AMI from 2010 to 2019 were included. They were stratified according to DM status, then grouped into three cohorts using a propensity score matching: non-DM patients; DM patients treated with GLP-1 RA and/or SGLT-2i; DM patients not treated with GLP-1 RA/SGLT-2i. The primary endpoint of the study was the composite of in-hospital mortality, acute heart failure, and acute kidney injury requiring renal replacement therapy. RESULTS: We identified 146,798 patients hospitalized with AMI (mean age 71 ± 13 years, 34% females, 47% STEMI; 26% with DM). After matching, 3,090 AMI patients (1030 in each group) were included in the analysis. Overall, the primary endpoint rate was 16% (n = 502) and progressively increased from non-DM patients to DM patients treated with and without GLP-1 RA/SGLT-2i (13%, 16%, and 20%, respectively; P < 0.0001). Compared with non-DM patients, DM patients with GLP-1 RA/SGLT-2i had a 30% higher risk of the primary endpoint, while those not treated with GLP-1 RA/SGLT-2i had a 60% higher risk (P < 0.0001). CONCLUSION: Chronic therapy with GLP-1 RA and/or SGLT-2i has a favorable impact on the clinical outcome of DM patients hospitalized with AMI.

Prognostic Impact of Percutaneous Coronary Intervention in Chronic Dialysis Patients with Acute Myocardial Infarction: Findings from the Lombardy Health Database.

Background: Patients on chronic dialysis are less likely to be treated with percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). This is due to the lack of evidence from randomized trials, concerns about possible PCI-related side effects, and multimorbidity. Therefore, routine use of PCI for treatment of dialysis patients with AMI remains an unresolved issue. Methods: We analyzed data of patients on chronic dialysis hospitalized with AMI from 2003 to 2018, by using the administrative Lombardy Health Database (Italy). Patients were grouped according to whether they underwent or not PCI during index hospitalization. The primary outcome was in-hospital mortality, 1-year mortality was the secondary endpoint. Results: During the study period, 265,048 patients were hospitalized with AMI. Of them, 3206 (1.2%) were on chronic dialysis (age 71 ± 11; 72% males). Among dialysis patients, 44% underwent PCI, while 54% underwent PCI among non-dialysis patients (p < 0.0001). Dialysis was an independent predictor of treatment with medical therapy only (OR 0.75 [95% CI 0.70-0.81]). In-hospital mortality in the dialysis cohort was 15%, significantly lower in patients treated with PCI than in those not treated with PCI (11% vs. 19%; p < 0.0001). One-year mortality was 47% and it was lower in PCI-treated patients (33% vs. 52%; p < 0.0001). The adjusted risk of the study endpoints was significantly lower in dialysis patients undergoing PCI: OR 0.62 (95% CI 0.50-0.76) for in-hospital mortality; HR 0.63 (95% CI 0.56-0.71) for 1-year mortality. Conclusions: This study showed that in AMI patients on chronic dialysis, PCI is associated with a significant in-hospital and 1-year survival benefit. Yet, they underwent PCI less frequently than patients with preserved renal function.

COVID-19-associated Guillain-Barré syndrome in the early pandemic experience in Lombardia (Italy).

OBJECTIVE: To estimate the incidence and describe clinical characteristics and outcome of GBS in COVID-19 patients (COVID19-GBS) in one of the most hit regions during the first pandemic wave, Lombardia. METHODS: Adult patients admitted to 20 Neurological Units between 1/3-30/4/2020 with COVID19-GBS were included as part of a multi-center study organized by the Italian society of Hospital Neuroscience (SNO). RESULTS: Thirty-eight COVID19-GBS patients had a mean age of 60.7 years and male frequency of 86.8%. CSF albuminocytological dissociation was detected in 71.4%, and PCR for SARS-CoV-2 was negative in 19 tested patients. Based on neurophysiology, 81.8% of patients had a diagnosis of AIDP, 12.1% of AMSAN, and 6.1% of AMAN. The course was favorable in 76.3% of patients, stable in 10.5%, while 13.2% worsened, of which 3 died. The estimated occurrence rate in Lombardia ranges from 0.5 to 0.05 GBS cases per 1000 COVID-19 infections depending on whether you consider positive cases or estimated seropositive cases. When we compared GBS cases with the pre-pandemic period, we found a reduction of cases from 165 to 135 cases in the 2-month study period in Lombardia. CONCLUSIONS: We detected an increased incidence of GBS in COVID-19 patients which can reflect a higher risk of GBS in COVID-19 patients and a reduction of GBS events during the pandemic period possibly due to a lower spread of more common respiratory infectious diseases determined by an increased use of preventive measures.

Detecting early signals of COVID-19 outbreaks in 2020 in small areas by monitoring healthcare utilisation databases: first lessons learned from the Italian Alert_CoV project.

BackgroundDuring the COVID-19 pandemic, large-scale diagnostic testing and contact tracing have proven insufficient to promptly monitor the spread of infections.AimTo develop and retrospectively evaluate a system identifying aberrations in the use of selected healthcare services to timely detect COVID-19 outbreaks in small areas.MethodsData were retrieved from the healthcare utilisation (HCU) databases of the Lombardy Region, Italy. We identified eight services suggesting a respiratory infection (syndromic proxies). Count time series reporting the weekly occurrence of each proxy from 2015 to 2020 were generated considering small administrative areas (i.e. census units of Cremona and Mantua provinces). The ability to uncover aberrations during 2020 was tested for two algorithms: the improved Farrington algorithm and the generalised likelihood ratio-based procedure for negative binomial counts. To evaluate these algorithms' performance in detecting outbreaks earlier than the standard surveillance, confirmed outbreaks, defined according to the weekly number of confirmed COVID-19 cases, were used as reference. Performances were assessed separately for the first and second semester of the year. Proxies positively impacting performance were identified.ResultsWe estimated that 70% of outbreaks could be detected early using the proposed approach, with a corresponding false positive rate of ca 20%. Performance did not substantially differ either between algorithms or semesters. The best proxies included emergency calls for respiratory or infectious disease causes and emergency room visits.ConclusionImplementing HCU-based monitoring systems in small areas deserves further investigations as it could facilitate the containment of COVID-19 and other unknown infectious diseases in the future.

Protective action of natural and induced immunization against the occurrence of delta or alpha variants of SARS-CoV-2 infection: a test-negative case-control study.

BACKGROUND: The evolution of SARS-CoV-2 has led to the emergence of several new variants, and few data are available on the impact of vaccination on SARS-CoV-2 variants. We aimed to assess the association between natural (previous infection) and induced (partial or complete vaccination) exposure to SARS-CoV-2 and the onset of new infection supported by the delta variant, and of comparing it with that supported by alpha. METHODS: We performed a test-negative case-control study, by linking population-based registries of confirmed diagnoses of infection with SARS-CoV-2, vaccinations against Covid-19 and healthcare utilization databases of the Italian Lombardy Region. Four hundred ninety-six persons who between 27 December 2020 and 16 July 2021 had an infection by the delta variant were 1:1 matched with citizens affected by alphavariant and 1:10 matched with persons who had a negative molecular test, according to gender, age and date of molecular ascertainment. We used a conditional logistic regression for estimating relative risk reduction of either variants associated with natural and/or induced immunization and corresponding 95% confidence interval (CI). RESULTS: Previous infection was associated with 91% (95% CI 85% to 95%) reduced relative risk of reinfection, without evidence of significant differences between delta and alpha cases (p=0.547). Significant lower vaccinal protection against delta than alpha variant infection was observed with reduced relative risk associated with partial vaccination respectively of 29% (7% to 45%), and 62% (48% to 71%) (p=0.001), and with complete vaccination respectively of 75% (66% to 82%) and 90% (85% to 94%) (p=0.003). CONCLUSIONS: Lower protection towards infections caused by the delta variant with respect to alpha variant was noticed, even after the completion of the vaccination cycle. This finding would support efforts to maximize both vaccine uptake with two doses and fulfilment with individual protection measures, especially as the delta variant is rampant worldwide presently.

Factors associated with severe or fatal clinical manifestations of SARS-CoV-2 infection after receiving the third dose of vaccine.

BACKGROUND: Little is known about vulnerability to severe COVID-19 illness after vaccination completion with three doses of vaccine against COVID-19. OBJECTIVES: To identify individual features associated with increased risk of severe clinical manifestation of SARS-CoV-2 infections after receiving the third dose of vaccine against COVID-19. METHODS: We performed a nested case-control study based on 3,360,116 citizens from Lombardy, Italy, aged 12 years or older who received the third dose of vaccine against COVID-19 from 20 September through 31 December 2021. Individuals were followed from 14 days after vaccination completion until the occurrence of severe COVID-19 illness, death unrelated to COVID-19, emigration or 15 March 2022. For each case, controls were randomly selected to be 1:10 matched for the date of vaccination completion and municipality of residence. The association between candidate predictors and outcome was assessed through multivariable conditional logistic regression models. RESULTS: During 12,538,330 person-months of follow-up, 5171 cases of severe illness occurred. As age increased, a trend towards increasing odds of severe illness was observed. Male gender was a significant risk factor. As the number of contacts with the Regional Health Service increased, a trend towards increasing odds of severe illness was observed. Having had a previous SARS-CoV-2 infection was a significant protective factor. Having received the Moderna vaccine significantly decreased the odds of severe illness. Significant higher odds were associated with 42 diseases/conditions. Odds ratios ranged from 1.23 (diseases of the musculoskeletal system) to 5.00 (autoimmune disease). CONCLUSIONS: This study provides useful insights for establishing priority in fourth-dose vaccination programs.

Increased risk of myocarditis and pericarditis and reduced likelihood of severe clinical outcomes associated with COVID-19 vaccination: a cohort study in Lombardy, Italy.

INTRODUCTION: We aimed to assess harms (post-vaccine myocarditis and pericarditis) and benefits (preventing severe disease) of COVID-19 vaccination. METHODS: We conducted a population-based retrospective cohort study. Using the integrated platform of the vaccination campaign of Lombardy Region (Italy), after the exclusion of 24,188 individuals not beneficiaries of the Regional Health Service, 9,184,146 citizens candidates to vaccine at December 27, 2020 were followed until November 30, 2021 (the loss to follow-up rate was 0.5%). From the date of administration of each vaccine dose to day 28 post-administration, three periods that covered exposure to the first, second, and third dose were defined. The benefit-risk profile of vaccines was performed by comparing the number needed to harm (NNH) and number needed to treat (NNT) by sex, age, and vaccine type. RESULTS: Incidence rates of myocarditis were 9.9 and 5.2 per million person-months during the exposure and no-exposure periods, respectively, and the incidence rates of pericarditis were 19.5 and 15.9 per million person-months, respectively. The risk of myocarditis was highest following exposure to the second dose of the Moderna vaccine (adjusted HR: 5.5, 95% CI: 3.7 to 8.1). Exposure to the Moderna vaccine was also associated with an increased risk of pericarditis (adjusted HR 2.2, 1.5 to 3.1). NNT was higher than NNH (9471 vs. 7213) for 16 to 19-year-old men who received the Moderna vaccine, while all other sex, age, and vaccine subgroups had a favourable harm-benefit profile. CONCLUSIONS: Men 16 to 19 years of age has the highest rates of myocarditis within a few days after receiving the Moderna vaccines. The balance between harms and benefits was almost always in favour of vaccination.

Access to SARS-CoV-2 diagnostic tests: are there barriers for the immigrants in Italy?

OBJECTIVES: to describe the epidemiology of SARS-CoV-2 infection in relation with the use of nasal swabs in the immigrant population in Italy, using data from the COVID-19 national surveillance system and to verify if a difference is present comparing natives and immigrant. DESIGN: descriptive study based on longitudinal health-administrative data. SETTING AND PARTICIPANTS: general population of six Italian Regions (Piedmont, Lombardy, Veneto, Emilia-Romagna, Tuscany, Lazio) covering about 55% of the resident population and 72% of foreigners' population. MAIN OUTCOME MEASURES: regional rates of access to at least a nasal swab, separately by country of origin. RESULTS: across all the periods, a lower rate in the foreigners' group was observed, with the only exception of the period May-June 2021. Considering separately High Migratory Pressure Countries (HMPCs) and Highly Developed Countries (HDCs), a higher proportion of nasal swabs performed in people coming from HDC with respect to HMPCs and natives was noticed. This observation is consistent in males and females. CONCLUSIONS: during the first wave of the pandemic, Italians have had a higher proportion of nasal swabs compared to migrants across all Regions. This difference disappeared in the following periods, probably due to a major availability of diagnostic tests.

[SARS-CoV-2 epidemic among Italians e resident immigrant population: differential incidence from an interregional multicentre study]. / L'epidemia di SARS-CoV-2 nella popolazione italiana e straniera: differenze di incidenza che emergono da uno studio multicentrico interregionale.

OBJECTIVES: to describe differences in the incidence of SARS-CoV-2 infections between Italians and foreigners residing in seven Italian Regions during the different phases of the pandemic and by gender. DESIGN: retrospective observational study. SETTING AND PARTICIPANTS: all confirmed SARS-CoV-2 infections from 02.02. 2020 to 16.07.2021 in the seven Regions under study were included. Italian resident population calculated by the National Institute of Statistics as of 01.01.2020 was used to calculate the rates. The considered period is divided into 5 sub-periods (phases). MAIN OUTCOME MEASURES: number of confirmed SARS-CoV-2 infections in the five phases of the pandemic and crude rates by citizenship (Italian vs foreign). Distribution of infections by age group and by week. Crude and age-adjusted incidence rates ratios (IRR) were calculated, by Region, gender, and phase of the pandemic. RESULTS: an epidemic curve delay was observed in foreigners in the first phase of the epidemic, in particular in the northern Regions, the most affected in that phase. The first phase of the epidemic was characterized by a greater proportion of cases occurred in people aged over 60 years than the other phases, both in Italians and in foreigners. The incidence among foreigners is higher during the summer of 2020 (intermediate period: June-September 2020) and during the last period (May-July 2021) in all Regions. The overall figure shows a lower incidence among foreigners than Italians, except for males in Tuscany. CONCLUSIONS: the lower incidence rates among foreigners should be interpreted with caution as the available data suggest that it is at least partly attributable to less access to diagnostic tests. Regional differences found in the study deserve further research together with the effect of gender and country of origin.

Characteristics and outcomes of patients with cancer hospitalized with new onset acute heart failure.

AIMS: Limited evidence exists regarding the outcomes of cancer patients hospitalized with new onset acute heart failure (AHF). We assessed the in-hospital mortality and 1 year outcomes of cancer patients admitted for new onset AHF, taking into account both past and active cancer status as well as cancer site. METHODS: We examined administrative data of adult patients hospitalized with a first episode of AHF from 2003 to 2018 in Lombardy, Italy. Patients were categorized based on their cancer history. The primary endpoint was in-hospital mortality with secondary endpoints including 1 year all-cause mortality and 1 year re-hospitalization for AHF. RESULTS: Among 283 144 patients AHF hospitalizations, 55 145 (19%) involved patients with a history of cancer (60% past cancer, 40% active cancer). Both in-hospital and 1 year mortality rates were higher among cancer patients compared with those without (9.3% vs. 6.4% and 34.9% vs. 22.3%, respectively; P < 0.0001). After adjustment, cancer patients exhibited increased risk of in-hospital mortality [odds ratio (OR) 1.40; 99% confidence interval (CI) 1.34-1.46] and 1 year mortality (HR 1.35; 99% CI 1.32-1.39), particularly among those with lung cancer. Patients with active and past cancer had a similar in-hospital mortality risk (OR 0.99; 99% CI 0.91-1.07) while 1 year mortality risk was higher among those with active cancer (HR 1.26; 99% CI 1.21-1.31). CONCLUSIONS: Cancer is a prevalent comorbidity in patients hospitalized with new onset AHF, and it is associated with a poorer prognosis. Mortality risk appears to vary based on cancer status and type.

Development and validation of an electronic database-based frailty index to predict mortality and hospitalization in a population-based study of adults with SARS-CoV-2.

Background: Electronic health databases are used to identify people at risk of poor outcomes. Using electronic regional health databases (e-RHD), we aimed to develop and validate a frailty index (FI), compare it with a clinically based FI, and assess its association with health outcomes in community-dwellers with SARS-CoV-2. Methods: Data retrieved from the Lombardy e-RHD were used to develop a 40-item FI (e-RHD-FI) in adults (i.e., aged ≥18 years) with a positive nasopharyngeal swab polymerase chain reaction test for SARS-CoV-2 by May 20, 2021. The considered deficits referred to the health status before SARS-CoV-2. The e-RHD-FI was validated against a clinically based FI (c-FI) obtained from a cohort of people hospitalized with COVID-19 and in-hospital mortality was evaluated. e-RHD-FI performance was evaluated to predict 30-day mortality, hospitalization, and 60-day COVID-19 WHO clinical progression scale, in Regional Health System beneficiaries with SARS-CoV-2. Results: We calculated the e-RHD-FI in 689,197 adults (51.9% females, median age 52 years). On the clinical cohort, e-RHD-FI correlated with c-FI and was significantly associated with in-hospital mortality. In a multivariable Cox model, adjusted for confounders, each 0.1-point increment of e-RHD-FI was associated with increased 30-day mortality (Hazard Ratio, HR 1.45, 99% Confidence Intervals, CI: 1.42-1.47), 30-day hospitalization (HR per 0.1-point increment = 1.47, 99%CI: 1.46-1.49), and WHO clinical progression scale (Odds Ratio = 1.84 of deteriorating by one category, 99%CI 1.80-1.87). Conclusion: The e-RHD-FI can predict 30-day mortality, 30-day hospitalization, and WHO clinical progression scale in a large population of community-dwellers with SARS-CoV-2 test positivity. Our findings support the need to assess frailty with e-RHD.

Natural and vaccine-induced immunity are equivalent for the protection against SARS-CoV-2 infection.

OBJECTIVES: To compare the long-term cumulative risk of SARS-CoV-2 infection associated with natural and vaccine-induced immunity. METHODS: Retrospective population-based cohort study based on registry of COVID-19 vaccinations and SARS-CoV-2 infections among 9.1 million citizens of Lombardy, Italy, eligible for vaccination on 27th December 2020. Those who developed SARS-CoV-2 infection from 24th May to 14th September 2021, provided they did not yet receive the COVID-19 vaccine when infection was confirmed, and those who received the second mRNA vaccine dose, provided they had not yet developed the infection, were selected to be 1:1 matched for sex, age and index date. The latter corresponded to 90 days after confirmed infection or 14 days after vaccine administration. A control cohort including citizens who, on the index date, had neither developed infection nor received vaccination was also selected. Kaplan-Meier curves were used for comparing the cumulative incidence of new SARS-CoV-2 infection from the index date until 22nd June 2022. RESULTS: Overall, 19,418 1:1:1 risk-sets were included. After 9 months of follow-up, the cumulative risk of new SARS-CoV-2 infection was 21.8%, 22.0%, and 25.9%, respectively, among exposed to natural immunity, vaccine-induced immunity and unexposed. CONCLUSIONS: Equivalent potential for protecting against new SARS-CoV-2 infection was observed.

Prognostic Impact of Percutaneous Coronary Intervention in Older Patients Hospitalized with Acute Myocardial Infarction: Real-World Findings from the Lombardy Health Database.

BACKGROUND: Older patients are less likely to receive percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) compared to younger patients. We investigated the prognostic impact of PCI in a large population of patients hospitalized with AMI in the period 2003-2018 by using the administrative Lombardy Health Database (Italy). METHODS: We considered all patients aged ≥75 years hospitalized with AMI (either STEMI or NSTEMI) from 2003 to 2018 in Lombardy. Patients were grouped according to whether they were treated or not with PCI during the index hospitalization. The primary outcome was in-hospital mortality. The secondary endpoints were 1-year mortality and 1-year re-hospitalization for acute heart failure (AHF) or AMI. RESULTS: 116,063 patients aged ≥75 years (mean age 83 ± 6; 48% males; 46% STEMI) were hospitalized with a primary diagnosis of AMI. Thirty-seven percent of them (n = 42,912) underwent PCI. The in-hospital mortality rate was significantly lower in PCI-treated patients (6% vs. 15%; p < 0.0001). One-year mortality and 1-year re-hospitalization for AHF/AMI were less frequent in PCI-treated patients (16% vs. 41% and 15% vs. 21%, respectively; p < 0.0001). The adjusted risks of the study endpoints were lower in PCI-treated patients: OR 0.37 (95% CI 0.36-0.39) for in-hospital mortality; HR 0.37 (95% CI 0.36-0.38) for 1-year mortality; HR 0.74 (95% CI 0.71-0.77) for 1-year re-hospitalization for AHF/AMI. Similar results were found in STEMI and NSTEMI patients considered separately. CONCLUSIONS: Our real-world data showed that in patients with AMI ≥ 75 years of age, PCI use is associated with lower in-hospital and 1-year mortality.

Early Detection of SARS-CoV-2 Epidemic Waves: Lessons from the Syndromic Surveillance in Lombardy, Italy.

We evaluated the performance of the exponentially weighted moving average (EWMA) model for comparing two families of predictors (i.e., structured and unstructured data from visits to the emergency department (ED)) for the early detection of SARS-CoV-2 epidemic waves. The study included data from 1,282,100 ED visits between 1 January 2011 and 9 December 2021 to a local health unit in Lombardy, Italy. A regression model with an autoregressive integrated moving average (ARIMA) error term was fitted. EWMA residual charts were then plotted to detect outliers in the frequency of the daily ED visits made due to the presence of a respiratory syndrome (based on coded diagnoses) or respiratory symptoms (based on free text data). Alarm signals were compared with the number of confirmed SARS-CoV-2 infections. Overall, 150,300 ED visits were encoded as relating to respiratory syndromes and 87,696 to respiratory symptoms. Four strong alarm signals were detected in March and November 2020 and 2021, coinciding with the onset of the pandemic waves. Alarm signals generated for the respiratory symptoms preceded the occurrence of the first and last pandemic waves. We concluded that the EWMA model is a promising tool for predicting pandemic wave onset.

Persistence of protection against SARS-CoV-2 clinical outcomes up to 9 months since vaccine completion: a retrospective observational analysis in Lombardy, Italy.

BACKGROUND: Scarce information is available on the duration of the protective effect of COVID-19 vaccination against the risk of SARS-CoV-2 infection and its severe clinical consequences. We investigated the effect of time since vaccine completion on the SARS-CoV-2 infection and its severe forms. METHODS: In this retrospective observational analysis using the vaccination campaign integrated platform of the Italian region of Lombardy, 5 351 085 individuals aged 12 years or older who received complete vaccination from Jan 17 to July 31, 2021, were followed up from 14 days after vaccine completion until Oct 20, 2021. Changes over time in outcome rates (ie, SARS-CoV-2 infection and severe illness among vaccinated individuals) were analysed with age-period-cohort models. Trends in vaccine effectiveness (ie, outcomes comparison in vaccinated and unvaccinated individuals) were also measured. FINDINGS: Overall, 14 140 infections and 2450 severe illnesses were documented, corresponding to incidence rates of 6·7 (95% CI 6·6-6·8) and 1·2 (1·1-1·2) cases per 10 000 person-months, respectively. From the first to the ninth month since vaccine completion, rates increased from 4·6 to 10·2 infections, and from 1·0 to 1·7 severe illnesses every 10 000 person-months. These figures correspond to relative reduction of vaccine effectiveness of 54·9% (95% CI 48·3-60·6) for infection and of 40·0% (16·2-57·0) for severe illness. The increasing infection rate was greater for individuals aged 60 years or older who received adenovirus-vectored vaccines (from 4·0 to 23·5 cases every 10 000 person-months). The increasing severe illness rates were similar for individuals receiving mRNA-based vaccines (from 1·1 to 1·5 every 10 000 person-months) and adenovirus-vectored vaccines (from 0·5 to 0·9 every 10 000 person-months). INTERPRETATION: Although the risk of infection after vaccination, and even more of severe illness, remains low, the gradual increase in clinical outcomes related to SARS-CoV-2 infection suggests that the booster campaign should be accelerated and that social and individual protection measures against COVID-19 spread should not be abandoned. FUNDING: None.

Vulnerability Predictors of Post-Vaccine SARS-CoV-2 Infection and Disease-Empirical Evidence from a Large Population-Based Italian Platform.

We aimed to identify individual features associated with increased risk of post-vaccine SARS-CoV-2 infection and severe COVID-19 illness. We performed a nested case-control study based on 5,350,295 citizens from Lombardy, Italy, aged ≥ 12 years who received a complete anti-COVID-19 vaccination from 17 January 2021 to 31 July 2021, and followed from 14 days after vaccine completion to 11 November 2021. Overall, 17,996 infections and 3023 severe illness cases occurred. For each case, controls were 1:1 (infection cases) or 1:10 (severe illness cases) matched for municipality of residence and date of vaccination completion. The association between selected predictors (sex, age, previous occurrence of SARS-CoV-2 infection, type of vaccine received, number of previous contacts with the Regional Health Service (RHS), and the presence of 59 diseases) and outcomes was assessed by using multivariable conditional logistic regression models. Sex, age, previous SARS-CoV-2 infection, type of vaccine and number of contacts with the RHS were associated with the risk of infection and severe illness. Moreover, higher odds of infection and severe illness were significantly associated with 14 and 34 diseases, respectively, among those investigated. These results can be helpful to clinicians and policy makers for prioritizing interventions.

Pediatric interregional healthcare mobility in Italy.

BACKGROUND: The analysis of interregional healthcare mobility represents one of the main criteria for evaluating Regional Healthcare Systems, both in terms of its economic-financial relevance and the quality and satisfaction of the services provided. The aim of the study is to analyze healthcare mobility and its associated cost in Italy in 2019 for all children ≤ 14 years of age. METHODS: We collected data from the "Rapporto annuale sull'attività di ricovero ospedaliero - Dati SDO 2019" published by the Italian Ministry of Health. These data represent the tool for collecting information relating to all hospitalization services provided in accredited public and private hospitals present throughout the national territory. We collected data for all Italian regions and clustered them in two geographical areas: Center-North regions and South regions (including Sicily and Sardinia). We have analyzed the magnitude of the mobility of children among regions and in particular from the South to the Center-North and the relative cost of this interregional mobility. RESULTS:  The hospitalization rate of children residing in the South regions was higher than  that of children residing in the Center-North regions (13.9% vs 12.3%). Children residing in the South were more frequently treated in other regions than those living in the Center-North (11.9% vs 6.9%). Even considering the high complexity hospitalizations, children living in the South more frequently underwent treatment in other regions (21.3% vs 10.5% of the Center-North). The cost of passive mobility amounts to € 103.9 million for the South regions (15.1% of the total hospitalizations' expenditure) and the 87.1% of this cost refers to the mobility to the hospitals of Center-North. The cost of healthcare migration from South regions to other South regions was much lower (12.9%, equal to € 13.4 million). CONCLUSIONS: Healthcare mobility, while affecting all Italian regions, is particularly relevant in the South regions and indicates a lack of pediatric care, which should be strengthened by creating services that are currently not evenly distributed throughout the territory.