Public health genomics research in Italy: an overview of ongoing projects.

Public health genomics (PHG) aims to integrate advances in genomic sciences into healthcare for the benefit of the general population. As in many countries, there are various research initiatives in this field in Italy, but a clear picture of the national research portfolio has never been sketched. Thus, we aimed to provide an overview of current PHG research projects at the national or international level by consultation with Italian institutional and academic experts. We included 68 PHG projects: the majority were international projects in which Italian researchers participated (n = 43), mainly funded by the European Commission, while the remainder were national initiatives (N = 25), mainly funded by central government. Funding varied considerably, from € 50,000 to € 80,803,177. Three main research themes were identified: governance (N = 20); precision medicine (PM; N = 46); and precision public health (N = 2). We found that research activities are preferentially aimed at the clinical application of PM, while other efforts deal with the governance of the complex translation of genomic innovation into clinical and public health practice. To align such activities with national and international priorities, the development of an updated research agenda for PHG is needed.

How well does vaccine literacy predict intention to vaccinate and vaccination status? A systematic review and meta-analysis.

This review quantified the association of vaccine literacy (VL) and vaccination intention and status. PubMed, Scopus, and Web of Science were searched. Any study, published until December 2022, that investigated the associations of interest were eligible. For each outcome, articles were grouped according to the vaccine administrated and results were narratively synthesized. Inverse-variance random-effect models were used to compare standardized mean values in VL domain(s) between the two groups: individuals willing vs. unwilling to get vaccinated, and individuals vaccinated vs. unvaccinated. This review of 18 studies shows that VL strongly predicts the vaccination intention while its association with vaccination status is attenuated and barely significant, suggesting that other factors influence the actual vaccination uptake. However, given the scarce evidence available, the heterogeneity in the methods applied and some limitations of the studies included, further research should be conducted to confirm the role of VL in the vaccination decision-making process.

The Impact of Rotavirus Vaccination on Discharges for Pediatric Gastroenteritis in Italy: An Eleven Year (2009-2019) Nationwide Analysis.

In Italy, despite the documented positive effects of rotavirus (RV) vaccination on reducing the burden of RV disease, an updated national assessment of its impact on clinical outcomes is still lacking. This study aims to analyze the implementation of RV vaccination in Italy, evaluating its impact on discharges for acute pediatric gastroenteritis (AGE). A retrospective analysis, including hospital discharge records and data on vaccination coverage for children aged 0-71 months from 2009 to 2019, was conducted. We examined trends in hospital discharge standardized incidence before and after vaccine introduction using a negative binomial mixture model with fixed effects to evaluate the impact of universal vaccination. The percentage of vaccination coverage increased over the years, from <5% between 2009 and 2013 to 26% in 2017, reaching 70% in 2019. The standardized incidence of discharges decreased over the period from 16.6/100,000 inhabitants in 2009-2013 to 9.9/100,000 inhabitants in 2018-2019. In this phase, about 15% of the estimated hospital discharges were avoided compared with those estimated in the first phase. The implementation of RV vaccination reduced AGE incidence discharges in children aged 0-71 months. Further efforts are needed to continue monitoring the vaccination effect over time and to increase vaccination coverage.

Early Warning Systems for Emerging Profiles of Antimicrobial Resistance in Italy: A National Survey.

Antimicrobial resistance (AMR) national surveillance systems in Italy lack alert systems for timely detection of emerging profiles of AMR with potential relevance to public health. Furthermore, the existence of early warning systems (EWS) at subnational level is unclear. This study aims at mapping and characterizing EWS for microbiological threats available at regional level in Italy, focusing on emerging AMR, and at outlining potential barriers and facilitators to their development/implementation. To this end, a three-section, web-based survey was developed and administered to all Italian regional AMR representatives from June to August 2022. Twenty out of twenty-one regions and autonomous provinces (95.2%) responded to the survey. Among these, nine (45%) reported the implementation of EWS for microbiological threats at regional level, three (15%) reported that EWS are in the process of being developed, and eight (40%) reported that EWS are not currently available. EWS characteristics varied widely among the identified systems concerning both AMR profiles reported and data flow: the microorganisms most frequently included were extensively drug-resistant (XDR) Enterobacterales, with the lack of a dedicated regional IT platform reported in most cases. The results of this study depict a highly heterogeneous scenario and suggest that more efforts aimed at strengthening national AMR surveillance systems are needed.

Incidence of Healthcare-Associated Infections in a Neonatal Intensive Care Unit before and during the COVID-19 Pandemic: A Four-Year Retrospective Cohort Study.

The COVID-19 pandemic may have had an impact on healthcare-associated infection (HAI) rates. In this study, we analyzed the occurrence of HAIs in a neonatal intensive care unit (NICU) of the Umberto I teaching hospital in Rome before and during the pandemic. All infants admitted from 1 March 2018 to 28 February 2022 were included and were divided into four groups according to their admission date: two groups before the pandemic (periods I and II) and two during the pandemic (periods III and IV). The association between risk factors and time-to-first event was analyzed using a multivariable Cox regression model. Over the four-year period, a total of 503 infants were included, and 36 infections were recorded. After adjusting for mechanical ventilation, birth weight, sex, type of delivery, respiratory distress syndrome, and previous use of netilmicin and fluconazole, the multivariable analysis confirmed that being hospitalized during the pandemic periods (III and IV) was the main risk factor for HAI acquisition. Furthermore, a change in the etiology of these infections was observed across the study periods. Together, these findings suggest that patient management during the pandemic was suboptimal and that HAI surveillance protocols should be implemented in the NICU setting promptly.

Attitudes of University Students towards Mandatory COVID-19 Vaccination Policies: A Cross-Sectional Survey in Rome, Italy.

Mandatory vaccination (MV) against COVID-19 is a contentious topic. In this study, we used logistic regression models to identify attitudes among Sapienza University students towards MV for COVID-19. We considered three different scenarios: mandatory COVID-19 vaccination (MCV) for healthcare workers (HCWs) (Model 1), for all people aged ≥ 12 years (Model 2), and for admission to schools and universities (Model 3). We collected 5287 questionnaires over a six-month period and divided these into three groups (September-October 2021, November-December 2021, and January-February 2022). MCV for HCWs was the most strongly supported policy (69.8% in favour), followed by MCV for admission to schools and universities (58.3%), and MCV for the general population (54.6%). In a multivariable analysis, the models showed both similarities and differences. There was no association of socio-demographic characteristics with the outcomes, apart from being enrolled in non-healthcare courses, which negatively affected Models 2 and 3. A greater COVID-19 risk perception was generally associated with a more positive attitude towards MCV, although heterogeneously across models. Vaccination status was a predictor of being in favour of MCV for HCWs, whereas being surveyed in November-February 2022 favoured MCV for admission to schools and universities. Attitudes towards MCV were variable across policies; thus, to avoid unintended consequences, these aspects should be carefully considered by policymakers.

The Association of Health Literacy with Intention to Vaccinate and Vaccination Status: A Systematic Review.

Despite health literacy (HL) being recognized as a driver of health-promoting behavior, its influence on the vaccination decision-making process remains unclear. This study summarized current evidence on the association between HL and both intention to vaccinate and vaccination status. We searched PubMed, Scopus, and Web of Science, retrieving observational studies published until January 2022 that used HL-validated tools to investigate the above associations for any vaccine. Quality was assessed using the Newcastle-Ottawa scale. Twenty-one articles were included; of these, six investigated the intention to vaccinate and the remainder vaccination status. Articles on intention looked at SARS-CoV-2 vaccination using heterogeneous HL tools and were of high/fair quality. Vaccination status, mainly for influenza or pneumococcal vaccines, was explored using various HL tools; the quality was generally high. We found inconsistent results across and within vaccine types, with no clear conclusion for either vaccination intention or status. A weak but positive association was reported between a high HL level and influenza vaccination uptake for individuals aged more than 65 years. HL did not seem to significantly influence behavior towards vaccination. Differences in the methods used might explain these results. Further research is needed to investigate the role of HL in the vaccination decision-making process.

What Are the Effects of Vitamin A Oral Supplementation in the Prevention and Management of Viral Infections? A Systematic Review of Randomized Clinical Trials.

Vitamin A (VA) deficiency is associated with increased host susceptibility to infections, but evidence on its role in the prevention and management of viral infections is still lacking. This review aimed at summarizing the effects of VA supplementation against viral infections to support clinicians in evaluating supplemental treatments. PubMed, Scopus, and Web of Science were searched. Randomized clinical trials comparing the direct effects of VA oral supplementation in any form vs. placebo or standard of care in the prevention and/or management of confirmed viral infections in people of any age were included. A narrative synthesis of the results was performed. The revised Cochrane Risk-Of-Bias tool was used to assess quality. Overall, 40 articles of heterogeneous quality were included. We found data on infections sustained by Retroviridae (n = 17), Caliciviradae (n = 2), Flaviviridae (n = 1), Papillomaviridae (n = 3), Pneumoviridae (n = 4), and Paramyxoviridae (n = 13). Studies were published between 1987 and 2017 and mostly conducted in Africa. The findings were heterogeneous across and within viral families regarding virological, immunological, and biological response, and no meaningful results were found in the prevention of viral infections. For a few diseases, VA-supplemented individuals had a better prognosis and improved outcomes, including clearance of HPV lesions or reduction in some measles-related complications. The effects of VA oral supplementation seem encouraging in relation to the management of a few viral infections. Difference in populations considered, variety in recruitment and treatment protocols might explain the heterogeneity of the results. Further investigations are needed to better identify the benefits of VA administration.

Managing the introduction of genomic applications into the National Health Service: A special challenge for health technology assessment in Italy.

In recent years, the rapid proliferation of genomic tests for use in clinical practice has prompted healthcare systems to use a health technology assessment (HTA) approach to distinguish valuable from unwarranted applications. In this study, we narratively review the Italian HTA mechanisms for medical devices (MDs), both at the national and regional levels, and discuss the opportunity and benefits of extending them to genomic technologies, for which a dedicated assessment path was advocated by the National Plan for Public Health Genomics in 2017. We found that the National Health Technology Assessment Program for MDs, completed in 2019, had developed a structured pathway for the HTA of MDs; it established a hub-and-spoke structure, run by a governmental institution, and put in place transparent methodological procedures to cover all four HTA phases (i.e., proposal and prioritization, assessment, appraisal, and dissemination). However, several factors have hindered its adoption, and the regions are at different stages of its implementation. For these reasons, efforts should be made to ensure its effective deployment, both at national and regional levels. In addition, we argue that to harmonize the institutional roles and methodological procedures adopted, the time has come to concentrate resources on a single pathway for the assessment of all technologies that include both MDs and genomic applications.

What Went Wrong with the IMMUNI Contact-Tracing App in Italy? A Cross-Sectional Survey on the Attitudes and Experiences among Healthcare University Students.

The adoption of digital contact-tracing apps to limit the spread of SARS-CoV-2 has been sup-optimal, but studies that clearly identify factors associated with the app uptake are still limited. In April 2021, we administered a questionnaire to healthcare university students to investigate their attitudes towards and experiences of the IMMUNI app. A multivariable logistic regression model was built to identify app download predictors. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated. We surveyed 247 students. Most respondents (65.6%) had not downloaded IMMUNI, reporting as the main reason the perceived app uselessness (32.7%). In the multivariable analysis, being advised to use the app (aOR: 3.21, 95%CI: 1.80-5.73), greater fear of infecting others (aOR: 1.50, 95%CI: 1.01-2.23), and greater trust in the institutional response to the emergency (aOR: 1.33, 95%CI: 1.00-1.76) were positively associated with the outcome, whereas greater belief in the "lab-leak theory" of COVID-19 was a negative predictor (aOR: 0.75, 95%CI: 0.60-0.93). Major technical issues were reported by app users. Targeted strategies aimed at improving awareness of digital health applications should be devised. Furthermore, institutions should invest in the development of these technologies, to minimize technical issues and make them accessible to the entire population.

Acinetobacter baumannii Isolates from COVID-19 Patients in a Hospital Intensive Care Unit: Molecular Typing and Risk Factors.

Infections caused by Acinetobacter baumannii represent a major concern for intensive care unit (ICU) patients. However, the epidemiology of these infections among COVID-19 patients has not been fully explored. The aims of this study were (i) to characterize the clonal spread of A. baumannii among COVID-19 patients admitted to the ICU of the Umberto I hospital of Rome during the first year of the pandemic and (ii) to identify risk factors for its acquisition. Isolates were analysed by pulsed-field gel electrophoresis, and a multivariable regression model was constructed. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated. Overall, 193 patients were included, and 102 strains were analysed. All isolates had highly antibiotic-resistant profiles and derived from two genotypes. The cumulative incidence of A. baumannii acquisition (colonization or infection) was 36.8%. Patients with A. baumannii had higher mortality and length of stay. Multivariable analysis showed that previous carbapenem use was the only risk factor associated with A. baumannii acquisition (aOR: 4.15, 95% CI: 1.78-9.64). We documented substantial A. baumannii infections and colonization and high levels of clonal transmission. Given the limited treatment options, effective prevention and containment strategies to limit the spread of A. baumannii should be implemented.

Comparing the Occurrence of Healthcare-Associated Infections in Patients with and without COVID-19 Hospitalized during the Pandemic: A 16-Month Retrospective Cohort Study in a Hospital Intensive Care Unit.

The COVID-19 pandemic has increased the healthcare-associated infection (HAI) risk in intensive care unit (ICU) patients. However, a comparison between patients with and without COVID-19 in terms of HAI incidence has been rarely explored. In this study, we characterized the occurrence of HAI among patients with and without COVID-19 admitted to the ICU of the Umberto I hospital of Rome during the first 16 months of the pandemic and also identified risk factors for HAI acquisition. Patients were divided into four groups according to their ICU admission date. A multivariable conditional risk set regression model for multiple events was constructed for each admission period. Adjusted hazard ratios and 95% confidence intervals were calculated. Overall, 352 COVID-19 and 130 non-COVID-19 patients were included, and a total of 361 HAIs were recorded. We found small differences between patients with and without COVID-19 in the occurrence and type of HAI, but the infections in the two cohorts mostly involved different microorganisms. The results indicate that patient management was likely an important factor influencing the HAI occurrence during the pandemic. Effective prevention and control strategies to reduce HAI rates should be implemented.

Impact of hospital mergers: a systematic review focusing on healthcare quality measures.

BACKGROUND: Despite mergers have increasingly affected hospitals in the recent decades, literature on the impact of hospitals mergers on healthcare quality measures (HQM) is still lacking. Our research aimed to systematically review evidence regarding the impact of hospital mergers on HQM focusing especially on process indicators and clinical outcomes. METHODS: The search was carried out until January 2020 using the Population, Intervention, Comparison and Outcome model, querying electronic databases (MEDLINE, Scopus, Web Of Science) and refining the search with hand search. Studies that assessed HQM of hospitals that have undergone a merger were included. HQMs were analyzed through a narrative synthesis and a strength of the evidence analysis based on the quality of the studies and the consistency of the findings. RESULTS: The 16 articles, included in the narrative synthesis, reported inconsistent findings and few statistically significant results. All indicators analyzed showed an insufficient strength of evidence to achieve conclusive results. However, a tendency in the decrease of the number of beds, hospital staff and inpatient admissions and an increase in both mortality and readmission rate for acute myocardial infarction and stroke emerged in our analysis. CONCLUSIONS: In our study, there is no strong evidence of improvement or worsening of HQM in hospital mergers. Since a limited amount of studies currently exists, additional studies are needed. In the meanwhile, hospital managers involved in mergers should adopt a clear evaluation framework with indicators that help to periodically and systematically assess HQM ascertaining that mergers ensure and primarily do not reduce the quality of care.

Risk of SARS-CoV-2 infection in migrants and ethnic minorities compared with the general population in the European WHO region during the first year of the pandemic: a systematic review.

BACKGROUND: Migrants and ethnic minorities have suffered a disproportionate impact of the COVID-19 pandemic compared to the general population from different perspectives. Our aim was to assess specifically their risk of infection in the 53 countries belonging to the World Health Organization European Region, during the first year of the pandemic. METHODS: We conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO CRD42021247326). We searched multiple databases for peer-reviewed literature, published on Medline, Embase, Scisearch, Biosis and Esbiobase in 2020 and preprints from PubMed up to 29/03/2021. We included cross-sectional, case-control, cohort, intervention, case-series, prevalence or ecological studies, reporting the risk of SARS-CoV-2 infection among migrants, refugees, and ethnic minorities. RESULTS: Among the 1905 records screened, 25 met our inclusion criteria and were included in the final analysis. We found that migrants and ethnic minorities during the first wave of the pandemic were at increased exposure and risk of infection and were disproportionately represented among COVID-19 cases. However, the impact of COVID-19 on minorities does not seem homogeneous, since some ethnic groups seem to be more at risk than others. Risk factors include high-risk occupations, overcrowded accommodations, geographic distribution, social deprivation, barriers to access to information concerning preventive measures (due to the language barrier or to their marginality), together with biological and genetic susceptibilities. CONCLUSIONS: Although mixed methods studies will be required to fully understand the complex interplay between the various biological, social, and cultural factors underlying these findings, the impact of structural determinants of health is evident. Our findings corroborate the need to collect migration and ethnicity-disaggregated data and contribute to advocacy for inclusive policies and programmatic actions tailored to reach migrants and ethnic minorities.

The association between adherence to cancer screening programs and health literacy: A systematic review and meta-analysis.

The effectiveness of a cancer screening program relies on its adherence rate. Health literacy (HL) has been investigated among the factors that could influence such participation, but the findings are not always consistent. The aim of this meta-analysis was to summarize the evidence between having an adequate level of HL (AHL) and adherence to cancer screening programs. PubMed, Scopus, and Web of Science were searched. Cross-sectional studies, conducted in any country, that provided raw data, unadjusted or adjusted odds ratio (OR) on the associations of interest were included. The quality of the studies was assessed with the Newcastle-Ottawa Scale. Inverse-variance random effects methods were used to produce pooled ORs and their associated confidence interval (CI) stratified by time interval (e.g., undergoing screening in the last period, or at least once during lifetime) for each cancer type, considering unadjusted and adjusted estimates separately. A sensitivity analysis was performed for those studies providing more estimates. Overall, 15 articles of average-to-good quality were pooled. We found a significant association between AHL and higher screening participation for breast, cervical and colorectal cancer, independently of other factors, both overall (N = 7, aOR = 1.73; 95% CI: 1.27-2.36; N = 3, aOR = 1.64; 95% CI: 1.30-2.09; and N = 5, aOR = 1.25, 95% CI: 1.12-1.39, respectively) and in most time-stratified analyses. The sensitivity analyses confirmed these results. Health literacy seems to be critical for an effective cancer prevention. Given the high prevalence of illiterate people across the world, a long-term action plan is needed.

The effects of orally administered lactoferrin in the prevention and management of viral infections: A systematic review.

It has been demonstrated that lactoferrin (LF) plays a role in host defence, but evidence on its potential antiviral property from clinical studies is fragmented. Our systematic review aimed at identifying the effects of orally administered LF against virus infections. The systematic search was conducted on PubMed, Scopus, Web of Science, BioRxiv.org and ClinicalTrials.gov from database inception to 7th January 2021. Eligible articles investigated any virus family and provided data on the effects of orally administered LF of any origin in the prevention and/or management of confirmed viral infections in people of any age. A narrative synthesis of the results was performed. Quality was assessed with the Cochrane Risk-Of-Bias and ROBINS-1 tools. A total of 27 records were included, nine of which were registered protocols. We found data on Flaviviridae (n = 10), Retroviridae (n = 3), Coronaviridae (n = 2), Reoviridae (n = 2) and Caliciviridae (n = 1). Most published trials were at high risk of bias. The findings were heterogeneous across and within viral families regarding virological, immunological and biological response, with no clear conclusion. Some weak but positive results were reported about decrease of symptom severity and duration, or reduction in viral loads. Despite high tolerability, the effects of LF as oral supplement are still inconsistent, both in preventing and managing viral infections. Small sample sizes, variety in recruitment and treatment protocols, and low study quality may have contributed to such heterogeneity. Better-designed studies are needed to further investigate its potential benefits against viral infections, including SARS-CoV-2.

Time to Align: A Call for Consensus on the Assessment of Genetic Testing.

In this paper, we updated our 2018 systematic review aimed to identify and compare ad hoc designed frameworks for genetic testing evaluation. Overall, we identified 30 frameworks (29 in the first systematic review and one in the update): they were mainly based on the ACCE model, whereas a minority were adjustments of the more traditional Health Technology Assessment (HTA) approach. After discussing the strengths and weaknesses of the retrieved frameworks, this perspective calls for consensus on the assessment of genetic testing. In line with the recent European recommendations that encouraged the generation of comparable evidence across Member States, we believe that the time has come to align all the ideas that have emerged over the last few decades and find a sustainable and sharable tool for the evaluation of genetic and genomic applications. Therefore, we suggest stopping the evaluation of such technologies using ad hoc strategies-affected by validation, implementation, and adoption issues-and we propose to use a general HTA approach, particularly the European reference tool for the assessment of health technologies, the EUnetHTA HTA core model, that is built on solid theoretical and methodological principles and provides a comprehensive assessment of the technologies value.

COVID-19 Vaccine Hesitancy among Italian University Students: A Cross-Sectional Survey during the First Months of the Vaccination Campaign.

Achieving high levels of vaccination coverage against COVID-19 may be hindered by vaccine hesitancy. We quantified over time the prevalence of COVID-19 vaccine hesitancy among university students, investigated its determinants, and analyzed student attitudes, risk perceptions and compliance with preventive measures. The survey was administered online from 1 March to 30 June 2021. A multivariable logistic regression model was built to identify predictors of hesitancy. Overall, we collected 5369 questionnaires that were grouped into three survey periods (March, April-May, and May-June). The response rate ranged from 81.2% to 76.4%, whereas vaccine hesitancy ranged from 22% to 29%. Multivariable analysis showed that April-May participants had higher odds of hesitancy than March respondents. Other positive predictors were being male, not being a healthcare student, having a lower academic level, and not disclosing a political position. Conversely, higher levels of perceived COVID-19 severity, concern for the emergency, confidence in vaccine safety and effectiveness, and self-reported adherence to mask wearing indoors and outdoors were negatively associated with hesitancy. We found that vaccine hesitancy changed over time and in relation to several factors. Strategies aimed at increasing the students' awareness and engagement, restoring confidence in health authorities, and limiting disinformation around the vaccines should be devised.

Prior Antibiotic Therapy and the Onset of Healthcare-Associated Infections Sustained by Multidrug-Resistant Klebsiella pneumoniae in Intensive Care Unit Patients: A Nested Case-Control Study.

Epidemiological research has demonstrated direct relationships between antibiotic consumption and the emergence of multidrug-resistant (MDR) bacteria. In this nested case-control study, we assessed whether prior exposure to antibiotic therapy and its duration affect the onset of healthcare-associated infections (HAIs) sustained by MDR Klebsiella pneumoniae (MDR-Kp) in intensive care unit patients. Cases were defined as patients who developed an MDR-Kp HAI. Controls matched on sex and the length of intensive care unit (ICU) stay were randomly selected from the at-risk population. Any antibiotic agent received in systemic administration before the onset of infection was considered as antibiotic exposure. Multivariable conditional logistic regression analyses were performed to estimate the effect of prior exposure to each antibiotic class (Model 1) or its duration (Model 2) on the onset of HAIs sustained by MDR-Kp. Overall, 87 cases and 261 gender-matched controls were compared. In Model 1, aminoglycosides and linezolid independently increased the likelihood of developing an MDR-Kp HAI, whereas exposure to both linezolid and penicillins reduced the effect of linezolid alone. In Model 2, cumulative exposure to aminoglycosides increased the likelihood of the outcome, as well as cumulative exposures to penicillins and colistin, while a previous exposure to both penicillins and colistin reduced the influence of the two antibiotic classes alone. Our study confirms that aminoglycosides, penicillins, linezolid, and colistin may play a role in favoring the infections sustained by MDR-Kp. However, several double exposures in the time window before HAI onset seemed to hinder the selective pressure exerted by individual agents.