Background. Second-generation migrants represent a growing demographic in Italy, yet evidence on their health status and health-related behaviours remain limited. This study aims to investigate differences in self-rated health and lifestyle behaviours among children, adolescents, and young adults with at least one foreign-citizen parent compared to those with Italian-citizen parents. Methods. Data from the Italian Daily Life Aspects cross-sectional surveys (2015–2022) were analysed, including participants aged 0–29 years. Multivariable logistic regression models with household-clustered standard errors were used to estimate adjusted odds ratios (aORs) for non-good self-rated health, overweight/obesity, sedentary lifestyle, low fruit and vegetable consumption, at-risk alcohol use, and smoking, adjusting for demographic, socioeconomic, household, and contextual factors. Results. 84,797 participants were included (77,097 with both Italian parents and 7,700 with one foreign-citizen parent). No significant differences were observed in self-rated health between the two groups (aOR 1.05; 95% CI 0.93–1.18). Individuals with at least one foreign-citizen parent showed higher odds of overweight/obesity (aOR 1.15; 95% CI 1.07–1.24) and sedentary lifestyle (aOR 1.73; 95% CI 1.59–1.87). Conversely, they had lower odds of at-risk alcohol use (aOR 0.66; 95% CI 0.58–0.75) and smoking (aOR 0.85; 95% CI 0.76–0.95). No clear differences were found in fruit and vegetable consumption. Conclusions. While self-perceived health appears similar, young people with foreign-citizen parents in Italy exhibit a distinct behavioural profile, combining higher physical inactivity and excess weight risks with lower substance use. Culturally sensitive public health interventions should address behavioural risks while reinforcing existing protective factors within migrant families.

Ceftazidime/avibactam (CZA) resistance in KPC-producing Klebsiella pneumoniae is a critical public health threat, traditionally associated with in vivo selection. In this three-year study conducted in an Intensive Care Unit (ICU), we aimed to investigate the emergence of CZA-resistant (CZA-R) K. pneumoniae in patients treated with CZA, assessing the possible role of hospital outbreaks in dissemination. We analysed a three-year dataset of antibiotic consumption and K. pneumoniae isolates collected from ICU patients receiving CZA therapy. Whole-genome sequencing (Illumina/Oxford Nanopore) and epidemiological reconstruction were used to investigate resistance mechanisms, KPC variants, and transmission dynamics, including outbreak detection. Among 871 ICU patients, 17.9

Introduction:Genome sequencing (GS) and exome sequencing (ES) technologies have gained increasing attention in health economics for evaluating their clinical and public health introduction, but their complexity challenges traditional methods. This systematic review aimed to investigate and discuss full economic evaluations (EEs) of GS and ES in relation to health outcomes, with a focus on methodological issues. Methods:A systematic search of several databases was carried out (PROSPERO CRD42023430992). Quality was evaluated using the Quality of Health Economic Studies instrument. Key methodological features were investigated, and a narrative synthesis of the findings was performed after grouping studies by testing scope. Results:Overall, 12 recently published cost-utility analyses (CUAs) were included, assessing the use of GS/ES for guiding targeted therapy in oncology (N = 4) or major depressive disorder (N = 1), and diagnosing rare genetic diseases (N = 7). The findings suggested that GS/ES may be cost-effective for diagnosing rare diseases and may also be cost-effective for treatment guidance under favorable conditions. Methodological rigor tended to be higher in treatment guidance studies, whereas EEs in pediatric diagnostics faced greater challenges. Utility values were largely derived from a common survey using validated multi-attribute utility instruments, and studied on proxy conditions. Variability in perspectives, target populations, and costs limited comparability. To strengthen future EEs, standardized methodologies and long-term, real-world data on clinical and non-clinical benefits are needed. Conclusion:Traditional CUA approaches are essential to guide the implementation of new technologies, but they should be accommodated or complemented by alternative methods, innovative and comprehensive frameworks that capture the broader value of GS/ES and support their integration into clinical and public health practice.

Introduction As genomic medicine becomes increasingly integrated into routine healthcare, genetic/genomic (G/G) literacy has emerged as a key determinant of informed decision-making. However, evidence on how G/G literacy influences intentions to undergo testing or actual test uptake remains fragmented. This systematic review synthesizes current research on the association between G/G literacy and decisions regarding G/G testing. Methods Databases were searched up to February 2025. Inclusion criteria were observational studies assessing G/G literacy with validated or ad hoc measures and reporting its association with genomic testing intention or uptake. Quality assessment and data extraction were conducted independently by multiple reviewers. A narrative synthesis of the findings was performed (PROSPERO CRD420250654819). Results Seven recently published (2019-2025) cross-sectional studies were included, spanning diverse countries and populations. Five studies examined testing intentions, while the remaining investigated testing uptake. Quality was variable. Most studies used Likert-scale measures for testing intention and single-item questions for uptake. Adjusted analyses using validated G/G tools consistently showed that higher G/G literacy was associated with greater testing intention across various contexts. Conversely, evidence for actual uptake was extremely limited and inconsistent. Specific dimensions of literacy, particularly familiarity with terms and communicative/critical skills, may play a greater role than factual knowledge alone. Conclusions Current evidence suggests that G/G literacy positively influences testing intention, while additional factors may contribute to actual test uptake. Given the paucity of evidence and some methodological limitations, standardized and longitudinal designs are needed to clarify these associations and inform interventions that support high-quality genomic decision-making. Practice implications Supporting testing decisions may require moving beyond knowledge-based approaches to focus on building familiarity with genomic terminology and addressing perceived benefits and barriers.

OBJECTIVES:The implementation of new applications into healthcare systems and practices frequently relies on health technology assessment (HTA). Given their complexity, HTA of genetic and genomic technologies (GGTs) faces multiple challenges; yet, no comprehensive synthesis exists. We systematically reviewed and summarized HTA challenges for GGTs, overall and by HTA domain. METHODS:Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched 3 databases (OSF protocol h4qg2). Eligible studies primarily discussed HTA challenges/barriers for GGTs across any HTA domain. Issues were classified into 9 EUnetHTA's Core Model domains plus a "framework" category. Results were synthesized narratively. RESULTS:Twenty records published between 2007 and 2025 were included: heterogeneous in structure, most discussed multiple HTA domains, and some reported suggestions. Economic (n = 12), clinical (n = 9), and social (n = 8) considerations predominated, whereas safety and organizational aspects were underrepresented. Across domains, we identified a persistent mismatch between the rapid evolution of GGTs and the slower generation of evidence, along with insufficient standardization and validation of key procedures that hinder cross-study comparability. Other major issues included defining clear healthcare pathways, valuing genomic testing, and strengthening regulatory frameworks to protect patient rights, data integrity, and equity of access. Suggested remedies were adopting living/rapid HTA, defining core outcome sets, harnessing real-world data sources, standardizing guidelines, engaging stakeholders, and enhancing national commitment. CONCLUSIONS:Fast-moving science and inadequate methods hamper HTA of GGTs. Adopting flexible HTA methods, standardized outcomes and procedures, and multistakeholder engagement, supported by national infrastructures, can shift HTA toward a more agile, resource-enabled system that better supports timely, generalizable, and equitable decision making in genomics.

OBJECTIVE:To examine the association between cancer literacy (CL) and cancer screening behaviors, including screening intention and uptake. METHODS:A comprehensive search was conducted across three databases up to October 2024 (CRD42024500935). Studies were included if they (i) had an observational design, (ii) measured CL using validated or ad hoc tools, and (iii) quantified its association with cancer screening intention and/or uptake. Quality was assessed using the Newcastle-Ottawa Scale. Findings were narratively synthesized by cancer type for each outcome. RESULTS:Six cross-sectional studies met the inclusion criteria: one focused on screening intention, four on screening uptake, and one on both outcomes. Data were available for breast, cervical, colorectal, prostate, and skin cancer. Study quality was heterogeneous, with most studies rated as fair quality and affected by methodological limitations, including reliance on self-reported data, imprecise outcome definitions and measurements, and heterogeneous target populations. While higher levels of CL were linked to increased screening intentions in both included studies, findings on screening uptake were inconsistent across and within cancer types, with significant associations more commonly observed in adjusted analyses. Although a few studies suggested that awareness of the importance of preventive measures may influence screening adherence, the overall results remained inconclusive across all cancer types. CONCLUSIONS:This review suggests a positive association between higher CL and cancer screening intentions, although the evidence is limited. The role of CL in screening uptake remains uncertain, indicating that additional factors may influence adherence. Given the limited evidence, methodological variability, and study limitations, further research employing more robust and standardized approaches is essential to better understand the role of CL in cancer-related behaviors. PRACTICAL IMPLICATIONS:Improving CL may have a role in shaping cancer screening behaviors, particularly in promoting screening intention. More rigorous research is needed to clarify the role of CL in screening behaviors.

Introduction. Oncological screenings and vaccinations are essential preventive strategies, yet participation in both remains suboptimal and variable. Methods. This pilot study examines the association between cervical cancer screening adherence and COVID-19 vaccination uptake among women aged 25-64 years in a large Local Health Authority in Rome, Italy, during 2021-2022. Analyzing data from 101,302 women, we identified a strong positive association between COVID-19 vaccination status and cervical screening participation, suggesting that common determinants influence both behaviors. Results. Age and area of residence also emerged as predictors of screening adherence, with lower participation observed among younger women and those living in central districts. Conclusions. Our findings highlight the need to foster a broader culture of prevention by integrating vaccination and screening efforts to improve public health outcomes. Enhancing health literacy and addressing shared barriers may increase participation in both programs. However, further research is needed to validate these findings, explore the underlying determinants of preventive behaviors, and develop targeted interventions to boost adherence to prevention programs.

Despite advances in precision medicine, the translation of genetic and genomic technologies into routine practice is hampered by a heterogeneous and limited evidence base and the absence of standardized evaluation methodologies. Health Technology Assessment (HTA) plays a critical role in bridging this gap, yet assessment approaches and comprehensiveness vary widely. This systematic review aims to map the landscape of the assessment reports on genetic and genomics applications, analyze their methodological aspects and identify gaps. PubMed, Scopus, Web of Science, and the international HTA database, were searched for assessment reports of genetic/genomic technologies. Information on reports general characteristics, assessment domains and their components, consulted sources of evidence and reported gaps was extracted. Findings were synthesized narratively. Out of 27,331 screened records, 41 reports were included, predominantly from Canada, the United Kingdom, and Australia, mainly aimed at informing policy making for single or multiple gene tests for cancer patients. Most reports used a generic HTA methodology and assessment domains varied across reports. Key clinical aspects, such as clinical accuracy and safety, suffered from evidence gaps (39.0

Background:The World Health Organization (WHO) recently advocated an urgent need for implementing national surveillance systems for the timely detection and reporting of emerging antimicrobial resistance (AMR). However, public information on the existing national early warning systems (EWSs) is often incomplete, and a comprehensive overview on this topic is currently lacking. Objective:This review aimed to map the availability of EWSs for emerging AMR in high-income countries and describe their main characteristics. Methods:A systematic review was performed on bibliographic databases, and a targeted search was conducted on national websites. Any article, report, or web page describing national EWSs in high-income countries was eligible for inclusion. EWSs were identified considering the emerging AMR-reporting WHO framework. Results:We identified 7 national EWSs from 72 high-income countries: 2 in the East Asia and Pacific Region (Australia and Japan), 3 in Europe and Central Asia (France, Sweden, and the United Kingdom), and 2 in North America (the United States and Canada). The systems were established quite recently; in most cases, they covered both community and hospital settings, but their main characteristics varied widely across countries in terms of the organization and microorganisms under surveillance, with also different definitions of emerging AMR and alert functioning. A formal system assessment was available only in Australia. Conclusions:A broader implementation and investment of national surveillance systems for the early detection of emerging AMR are still needed to establish EWSs in countries and regions lacking such capabilities. More standardized data collection and reporting are also advisable to improve cooperation on a global scale. Further research is required to provide an in-depth analysis of EWSs, as this study is limited to publicly available data in high-income countries.

Polygenic risk scores (PRSs) represent a promising innovation in the context of precision health, but their benefits for patients and healthcare systems remain unclear. This systematic review examined the methods used to quantify the costs and benefits of PRS-based approaches across different healthcare contexts, summarizing current evidence and identifying challenges. A systematic search of three databases was conducted, and full economic evaluations related to any intervention based on polygenic risk stratification strategies were included (PROSPERO CRD42023442780). Quality was assessed using the Quality of Health Economic Studies instrument. Studies were grouped into three categories (cancer, cardiovascular disease, and other diseases), and key methodological features and characteristics were extracted. A total of 24 cost-utility analyses of generally high quality were included: 16 studies focused on cancer, five on cardiovascular disease, and three on other diseases. Studies on cancer mainly aimed to optimize screening programs, while in the other fields, PRSs were mostly used to refine eligibility for preventive therapies. Analyses were robust, but they mostly relied on hypothetical cohorts, had limited generalizability, paid insufficient attention to implementation aspects-including the delivery model-and considered only clinical benefits. Despite a positive trend toward cost effectiveness following PRS implementation, several challenges remain. These include the limited use of real-world data, issues of representativeness, and gaps in accounting for implementation costs, as well as long-term health and non-health benefits. Further research and pilot studies are needed to evaluate both the costs and benefits of PRS applications across diverse populations for multiple health outcomes simultaneously.

Systematic reviews play a critical role in evidence-based research but are labor-intensive, especially during title and abstract screening. Compact large language models (LLMs) offer potential to automate this process, balancing time/cost requirements and accuracy. The aim of this study is to assess the feasibility, accuracy, and workload reduction by three compact LLMs (GPT-4o mini, Llama 3.1 8B, and Gemma 2 9B) in screening titles and abstracts. Records were sourced from three previously published systematic reviews and LLMs were requested to rate each record from 0 to 100 for inclusion, using a structured prompt. Predefined 25-, 50-, 75-rating thresholds were used to compute performance metrics (balanced accuracy, sensitivity, specificity, positive and negative predictive value, and workload-saving). Processing time and costs were registered. Across the systematic reviews, LLMs achieved high sensitivity (up to 100%) and low precision (below 10%) for records included by full text. Specificity and workload savings improved at higher thresholds, with the 50- and 75-rating thresholds offering optimal trade-offs. GPT-4o-mini, accessed via application programming interface, was the fastest model (~40 minutes max.) and had usage costs ($0.14–$1.93 per review). Llama 3.1-8B and Gemma 2-9B were run locally in longer times (~4 hours max.) and were free to use. LLMs were highly sensitive tools for the title/abstract screening process. High specificity values were reached, allowing for significant workload savings, at reasonable costs and processing time. Conversely, we found them to be imprecise. However, high sensitivity and workload reduction are key factors for their usage in the title/abstract screening phase of systematic reviews.

It is well known that, to be effective, vaccination programs require a high and consistent population uptake. Nevertheless, vaccine coverage is often insufficient. University students occupy a unique position within the broader population: they are highly mobile and socially active individuals who serve as influential figures among their peers and younger age groups, making them an ideal target for educational campaigns. This review (CRD42022309724) quantified the vaccination intention rates for routine immunizations in university students and systematically examined the determinants of vaccination acceptance. Cross-sectional studies that analyzed vaccination intention for at least one routine immunization using multivariable logistic regression were included. We used random-effects models to calculate the pooled proportions of vaccination intention. Determinants were categorized into contextual factors (such as socio-demographic, economic and cultural factors), individual/group factors (such as knowledge, awareness, peer opinions, infection risk perceptions) and vaccine-specific issues (such as vaccine effectiveness and vaccination policies). Thirty-six articles were included: 29 on the human papilloma virus (HPV) vaccine and seven on the influenza vaccine. The pooled proportion of students intending to get vaccinated was 54

Abstract Background The last decade has witnessed a steady embrace of Personalized Medicine. However, the evaluation of genetic/genomic tests is not straightforward. The purpose of this systematic review is to identify health technology assessment (HTA) reports assessing genetic and genomic tests, to summarize the methodologies used, the maturity level of the evidence included in it and the highlighted gaps in research. Methods PubMed, Scopus, and Web of Science were searched. Additionally, a desk research was performed on the main HTA reports repositories. HTA reports expressly created to assess genetic/genomic technologies including at least three core evaluation components (analytic validity, clinical validity, clinical utility, economic evaluation, organizational aspects, ethical, legal, and social implications) were included. This study was supported by the EC and MUR under PNRR - M4C2-I1.3 Project PE_00000019 ‘HEAL ITALIA’. Results Overall, 27331 unique records were retrieved, 55 of which were included in the systematic review. The reports were mainly from Australia (29%), Canada (27%) and UK (25%), regarded pharmacogenomics (36%) and oncology (35%), and analysed test use for treatment choice (29%) and diagnosis (13%). The most reported evaluation components were economic evaluation (87%), clinical utility (76%), and clinical validity (67%). Personal utility (7%), ethical (15%), legal (11%) and social (24%) implications and the patient’s perspective (27%) were poorly represented. Analytical validity, safety, and organizational aspects were included in about half of the reports. Discussion Although these are only preliminary results, the substantial lack of a shared standard in the evaluation of genetic/genomic applications appears clear, given the heterogeneity of the dimensions addressed between reports, as well as the need to strengthen the evaluation of the neglected dimensions, often of primary importance in the definition of the value and risks of personalized medicine. Key messages • The findings highlight the lack of a standard in evaluating genetic/genomic applications. • A common methodology should be developed to comprehensively evaluate genetic/genomic applications.

Abstract Background This study aimed at investigating the association between cancer literacy (CL) and adherence to cancer screening programs. Methods PubMed, Scopus and Web of Science were searched. Any study, published until March 2024, that investigated the associations between CL and cancer screening intention or uptake in any target population were eligible. For CL measurement, both validated and ad hoc tools were considered. For each outcome, articles were grouped according to the type of cancer investigated and results were narratively synthesized. Results A total of 3426 records were retrieved. After deduplication and screening process, six studies were included. Population enrolled was heterogeneous as well as the tool used to measure CL. Four studies explored the relationship between CL and screening uptake, one focused solely on screening intention and another investigated both intention and uptake. Significant association was found between CL and screening intention in the two studies included, with higher literacy levels correlating to increased intent for screening. A significant association between higher CL and skin cancer screening uptake was reported, while the uptake of prostate cancer screening was not significantly associated with CL levels. By contrast, mixed results were obtained investigating breast, cervix and colorectal screening uptake. Conclusions Higher levels of cancer literacy appeared to be associated with screening intention, while its association with screening uptake was found barely significant for any screening type, suggesting that other factors influence the actual screening uptake. However, the scarce number of studies, along with the absence of validated tools and the heterogeneity of target populations, limits the generalizability of the results. Further research, differentiating screening types and timelines and using multivariate models, is needed to clarify the role of CL in screening behaviours. Key messages • Higher levels of cancer literacy appear to be associated with screening intention, suggesting its importance in promoting motivation for early cancer detection. • Association between cancer literacy and screening uptake was found barely significant for any screening type, suggesting that other factors influence actual screening uptake, urging further research.

Stereotactic radiotherapy (SRT) is an established treatment for melanoma brain metastases (MBM). Recent evidence suggests that perilesional edema volume (PEV) might compromise the delivery and efficacy of radiotherapy to treat BM. This study investigated the association between SRT efficacy and PEV extent in MBM. This retrospective study reviewed medical records from January 2020 to September 2023. Patients with up to 5 measurable MBMs, intracranial disease per RANO/iRANO criteria, and on low-dose corticosteroids were included. MRI scans assessed baseline neuroimaging, with PEV analyzed using 3D Slicer. SRT plans were based on MRI-CT fusion, delivering 18–32.5 Gy in 1–5 fractions. Outcomes included intracranial objective response rate (iORR) and survival measures (L-iPFS and OS). Statistical analysis involved decision tree analysis and multivariable logistic regression, adjusting for clinical and treatment variables. Seventy-two patients with 101 MBM were analyzed, with a mean age of 68.83 years. The iORR was 61.4

To manage the number of critical COVID-19 patients, Umberto I Teaching Hospital in Rome established a temporary ICU on March 1, 2021. This study investigated the incidence and risk factors of healthcare-associated infections (HAIs) among these patients during various COVID-19 waves. Patients were grouped by admission date according to the dominant SARS-CoV-2 variant prevalent at the time (Alpha, Delta, Omicron BA.1, Omicron BA.2, Omicron BA.5, and Omicron XBB). First-HAI and mortality rates were calculated per 1000 patient-days. Predictors of first-HAI occurrence were investigated using a multivariable Fine–Gray regression model considering death as a competing event. Among 355 admitted patients, 27.3% experienced at least one HAI, and 49.6% died. Patient characteristics varied over time, with older and more complex cases in the later phases, while HAI and mortality rates were higher in the first year. Pathogens responsible for HAIs varied over time, with first Acinetobacter baumannii and then Klebsiella pneumoniae being progressively predominant. Multivariable analysis confirmed that, compared to Alpha, admission during the Omicron BA.1, BA.2, BA.5, and XBB periods was associated with lower hazards of HAI. Despite worsening COVID-19 patient conditions, late-phase HAI rates decreased, likely due to evolving pathogen characteristics, improved immunity, but also better clinical management, and adherence to infection prevention practices. Enhanced HAI prevention in emergency situations is crucial.

Abstract Introduction Evaluating genetic/genomic applications (GGAs) is crucial for their implementation in clinical practice but hindered by several issues, such as rapid development processes and unclear benefits. Since these challenges lack comprehensive discussion, this study aims to identify and analyze all barriers emerged in the Health Technology Assessment (HTA) of genetic/genomic tests, filling a gap in the current literature. Methods PubMed, Scopus and Web of Science were searched to identify studies that specifically discussed any challenge or barrier in the HTA evaluation of GGAs. No restriction was applied on evaluation aspect or study type. Challenges/barriers were then grouped into the domains outlined in the EUnetHTA Core Model. A narrative synthesis of the main findings was performed. This study was supported by the EC and MUR- PNRR-M4C2-I1.3 Project PE_00000019 ‘HEAL ITALIA’. Results 19 articles were included: one third involved experts from different countries, and about 50% were author perspectives. Articles either focused on one aspect only (37%) or were more general (47%). The most challenging domain was economic aspects (69%), followed by clinical effectiveness (47%) and social impact (42%), but issues were found in all domains. The lack of a standardized HTA approach, the paucity of evidence on clinical outcomes, the challenges in capturing all health benefits, and the difficulties in identifying the healthcare pathways triggered by the test were consistently mentioned across the HTA domains. Conclusions Our study systematically summarized challenges in the HTA evaluation of GGAS, providing a thorough analysis and categorization of these issues. Various challenges surfaced, notably related to the identification of costs, as well as clinical and non-clinical benefits. There is a need for exhaustive discussion on potential solutions to facilitate the assessment process of these technologies to ultimately foster their implementation in clinical practice. Key messages • There are multiple challenges in the HTA evaluation of genetic and genomic tests in clinical practice that impact every HTA domain. • There is a need for concrete efforts in generating further evidence in relation to the definition of costs and benefits of the healthcare pathways triggered by genetic/genomic applications.

Abstract Background An urgent need of implementing national surveillance systems for timely detection and reporting of emerging antimicrobial resistance (AMR) was recently advocated by the World Health Organization (WHO). However, public information on existing national early warning systems (EWSs) is often incomplete. Furthermore, when findings are available, understanding these systems is challenging due to different approaches used for data collection, reporting and definitions, with a comprehensive overview on this topic currently lacking. The aim of this study was to map existing EWSs for emerging AMR, focusing on high-income countries, and describe their main characteristics. Methods A systematic review was performed on bibliographic databases, and a targeted search was conducted on national websites. Any article, report or webpage describing national EWSs in high-income countries was eligible for inclusion. EWSs were identified considering the emerging AMR reporting WHO framework. Results We identified seven national EWSs in 72 high-income countries: two (Australia, Japan) in the East Asia and Pacific Region, three (France, Sweden, United Kingdom) in Europe and Central Asia, and two (United States, Canada) in North America. The systems were established quite recently; in most cases they covered both community and hospital settings, but their main characteristics varied widely across countries in terms of organization and microorganisms under surveillance, with also different definitions of emerging AMR and alert functioning. A formal system assessment was available only in Australia. Conclusions A broader implementation and investment of national surveillance systems that allow early detection of emerging AMR is still needed to establish EWSs in countries and regions lacking such capabilities. A more standardized data collection and reporting is also advisable to improve cooperation on a global scale. Key messages • This study provides a synthesis of publicly available information on national EWSs for emerging AMR in high-income countries, highlighting the urgent need for a broader implementation of such systems. • Main characteristics of EWSs have been outlined, varying widely across countries. Findings could help stakeholders in strengthening current standard national AMR surveillance systems.

Background: Acinetobacter baumannii (AB) poses a significant threat to critically ill patients in intensive care units (ICUs). Although an association between antibiotic exposure and resistant AB is reported in the literature, a synthesis of evidence in ICU patients is still lacking. Aim: To summarize the evidence on the association between prior antibiotic exposure and the occurrence of resistant AB in ICU patients. Methods: Online databases were searched for cohort and case-control studies providing data on the association of interest. Carbapenem/multidrug-resistant AB isolation was compared with non-isolation; carbapenem/multidrug-resistant AB was compared with carbapenem/antibiotic-susceptible AB; and extensively drug-resistant AB isolation was compared with non-isolation. Each comparison was subjected to a restricted maximum likelihood random-effects meta-analysis per antibiotic class, estimating pooled ORs. Stratified meta-analyses were performed by study design, outcome type and associationmeasure adjustment.Findings: Overall, 25 high-quality studies were retrieved. Meta-analyses showed that carbapenem/multidrug-resistant AB isolation was associated with previous exposure to aminoglycosides, carbapenems, third-generation cephalosporines, glycylcyclines, and nitroimidazoles. Increased risk of isolation of carbapenem/multidrug-resistant AB isolation vs carbapenem/antibiotic-susceptible AB was shown for prior exposure to aminoglycosides, antipseudomonal penicillins, carbapenems, fluoroquinolones, glycopeptides, and penicillins. Third-generation cephalosporin exposure increased the risk of extensively drug-resistant AB isolation vs non-isolation. Conclusion: This systematic review clarifies the role of antibiotic use in antibioticresistant AB spread in ICUs, although for some antibiotic classes the evidence is still uncertain due to the small number of adjusted analyses, methodological and reporting issues, and limited number of studies. Future studies need to be carried out with stand-ardized methods and appropriate reporting of multivariable models. 2023 The Authors. Published by Elsevier Ltd on behalf of The Healthcare Infection Society. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

IntroductionImplementation of polygenic risk scores (PRS) may improve disease prevention and management, but its benefits and costs are still to be quantified. The review aimed to summarize evidence on the economic evaluation of PRS, exploring how their use impacts healthcare resource utilization, cost outcomes, and overall cost-effectiveness in order to help guide healthcare decision-making and resource allocation.MethodsThe PubMed, Scopus, and Web of Science databases were searched. The search terms were constructed to identify full economic evaluations of healthcare programs containing PRS aimed at assessing the risk of diseases or other health outcomes in any target population. The search strategy was adapted to fit each database’s research criteria. The literature search was supplemented by scanning the reference lists of retrieved articles. No language or date restriction was applied. The database search was rerun just before the final analysis. This research was supported by the European Commission and the Ministry for Universities and Research under the National Recovery and Resilience Plan (M4C2-I1.3 Project PE_00000019 “HEAL ITALIA”).ResultsOf the 1,891 articles screened, seven economic evaluations were included. They were conducted between 2020 and 2022 in Asia (n=1), Australia (n=1), Europe (n=2), and the USA (n=3). The field of application was ophthalmology (n=2), oncology (n=1), cardiovascular (n=2), nephrology (n=1), and endocrinology (n=1). The time horizon was lifetime (57%) or between five and 40 years (43%). The most frequent viewpoint was the health system perspective (n=5). The target populations included healthy people or individuals at risk for a specific disease. Performing PRS tests was found to be a dominant strategy, with lower costs and better health outcomes in all studies.ConclusionsAlthough the integration of PRS in clinical practice seems to be a cost-effective strategy, the small number of studies available and the heterogeneity in the field of application and the target populations limits the generalizability of results. A health technology assessment approach could be useful for summarizing the evidence on all domains of PRS implementation.