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In the past decade, significant European calls for research proposals have supported translational collaborative research on non-communicable and infectious diseases within the biomedical life sciences by bringing together interdisciplinary and multinational consortia. This research has advanced our understanding of disease pathophysiology, marking considerable scientific progress. Yet, it is crucial to retrospectively evaluate these efforts’ societal impact. Research proposals should be thoughtfully designed to ensure that the research findings can be effectively translated into actionable policies. In addition, the choice of scientific methods plays a pivotal role in shaping the societal impact of research discoveries. Understanding the factors responsible for current unmet public health issues and medical needs is crucial for crafting innovative strategies for research policy interventions. A multistakeholder survey and a roundtable helped identify potential needs for consideration in the EU research and policy agenda. Based on survey findings, mental health disorders, metabolic syndrome, cancer, antimicrobial resistance, environmental pollution, and cardiovascular diseases were considered the public health challenges deserving prioritisation. In addition, early diagnosis, primary prevention, the impact of environmental pollution on disease onset and personalised medicine approaches were the most selected unmet medical needs. Survey findings enabled the formulation of some research-policies interventions (RPIs), which were further discussed during a multistakeholder online roundtable. The discussion underscored recent EU-level activities aligned with the survey-derived RPIs and facilitated an exchange of perspectives on public health and biomedical research topics ripe for interdisciplinary collaboration and warranting attention within the EU’s research and policy agenda. Actionable recommendations aimed at facilitating the translation of knowledge into transformative, science-based policies are also provided.

BackgroundCardiovascular diseases (CVDs) pose a significant global health challenge, necessitating innovative approaches for primary prevention. Personalized prevention, based on genetic risk scores (PRS) and digital technologies, holds promise in revolutionizing CVD preventive strategies. However, the clinical efficacy of these interventions requires further investigation. This study presents the protocol of the INNOPREV randomized controlled trial, aiming to evaluate the clinical efficacy of PRS and digital technologies in personalized cardiovascular disease prevention.MethodsThe INNOPREV trial is a four-arm RCT conducted in Italy. A total of 1,020 participants, aged 40–69 with high 10-year CVD risk based on SCORE 2 charts, will be randomly assigned to traditional CVD risk assessment, genetic testing (CVD PRS), digital intervention (app and smart band), or a combination of genetic testing and digital intervention. The primary objective is to evaluate the efficacy of providing CVD PRS information, measured at baseline, either alone or in combination with the use of an app and a smart band, on two endpoints: changes in lifestyle patterns, and modification in CVD risk profiles. Participants will undergo a comprehensive assessment and cardiovascular evaluation at baseline, with follow-up visits at one, five, and 12 months. Lifestyle changes and CVD risk profiles will be assessed at different time points beyond the initial assessment, using the Life's Essential 8 and SCORE 2, respectively. Blood samples will be collected at baseline and at study completion to evaluate changes in lipid profiles. The analysis will employ adjusted mixed-effect models for repeated measures to assess significant differences in the data collected over time. Additionally, potential moderators and mediators will be examined to understand the underlying mechanisms of behavior change.DiscussionAs the largest trial in this context, the INNOPREV trial will contribute to the advancement of personalized cardiovascular disease prevention, with the potential to positively impact public health and reduce the burden of CVDs on healthcare systems. By systematically examining the clinical efficacy of PRS and digital interventions, this trial aims to provide valuable evidence to guide future preventive strategies and enhance population health outcomes.

Introduction Prevention of cardiovascular disease (CVD) is of key importance in reducing morbidity, disability and mortality worldwide. Observational studies suggest that digital health interventions can be an effective strategy to reduce cardiovascular (CV) risk. However, evidence from large randomised clinical trials is lacking.Methods and analysis The CV-PREVITAL study is a multicentre, prospective, randomised, controlled, open-label interventional trial designed to compare the effectiveness of an educational and motivational mobile health (mHealth) intervention versus usual care in reducing CV risk. The intervention aims at improving diet, physical activity, sleep quality, psycho-behavioural aspects, as well as promoting smoking cessation and adherence to pharmacological treatment for CV risk factors. The trial aims to enrol approximately 80 000 subjects without overt CVDs referring to general practitioners’ offices, community pharmacies or clinics of Scientific Institute for Research, Hospitalization and Health Care (Italian acronym IRCCS) affiliated with the Italian Cardiology Network. All participants are evaluated at baseline and after 12 months to assess the effectiveness of the intervention on short-term endpoints, namely improvement in CV risk score and reduction of major CV risk factors. Beyond the funded life of the study, a long-term (7 years) follow-up is also planned to assess the effectiveness of the intervention on the incidence of major adverse CV events. A series of ancillary studies designed to evaluate the effect of the mHealth intervention on additional risk biomarkers are also performed.Ethics and dissemination This study received ethics approval from the ethics committee of the coordinating centre (Monzino Cardiology Center; R1256/20-CCM 1319) and from all other relevant IRBs and ethics committees. Findings are disseminated through scientific meetings and peer-reviewed journals and via social media. Partners are informed about the study’s course and findings through regular meetings.Trial registration number NCT05339841.

Summary: Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett’s oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture. Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO. Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level. Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO. Funding: German Research Foundation (DFG).

Abstract Background Risk prediction models incorporating single nucleotide polymorphisms (SNPs) could lead to individualized prevention of colorectal cancer (CRC). However, the added value of incorporating SNPs into models with only traditional risk factors is still not clear. Hence, our primary aim was to summarize literature on risk prediction models including genetic variants for CRC, while our secondary aim was to evaluate the improvement of discriminatory accuracy when adding SNPs to a prediction model with only traditional risk factors. Methods We conducted a systematic review on prediction models incorporating multiple SNPs for CRC risk prediction. We tested whether a significant trend in the increase of Area Under Curve (AUC) according to the number of SNPs could be observed, and estimated the correlation between AUC improvement and number of SNPs. We estimated pooled AUC improvement for SNP-enhanced models compared with non-SNP-enhanced models using random effects meta-analysis, and conducted meta-regression to investigate the association of specific factors with AUC improvement. Results We included 33 studies, 78.79% using genetic risk scores to combine genetic data. We found no significant trend in AUC improvement according to the number of SNPs (p for trend = 0.774), and no correlation between the number of SNPs and AUC improvement (p = 0.695). Pooled AUC improvement was 0.040 (95% CI: 0.035, 0.045), and the number of cases in the study and the AUC of the starting model were inversely associated with AUC improvement obtained when adding SNPs to a prediction model. In addition, models constructed in Asian individuals achieved better AUC improvement with the incorporation of SNPs compared with those developed among individuals of European ancestry. Conclusions Though not conclusive, our results provide insights on factors influencing discriminatory accuracy of SNP-enhanced models. Genetic variants might be useful to inform stratified CRC screening in the future, but further research is needed.

BackgroundAlthough physical activity (PA) has been recognized as a favourable factor in the prevention of various diseases, including certain forms of cancer, the relationship between PA and gastric cancer (GC) is not yet fully understood. This study aims to provide data from a pooled analysis of case-control studies within the Stomach cancer Pooling (StoP) Project to estimate the association between leisure-time PA and the occurrence of GC.MethodsSix case-control studies from StoP project collected data on leisure-time PA, for a total of 2,343 cases and 8,614 controls. Subjects were classified into three leisure-time PA categories, either none/low, intermediate or high, based on study-specific tertiles. We used a two-stage approach. Firstly, we applied multivariable logistic regression models to obtain study-specific odds ratios (ORs) and corresponding 95% confidence intervals (CIs) then, we used a random-effect models to obtain pooled effect estimates. We performed stratified analyses according to demographic, lifestyle and clinical covariates.ResultsThe meta-analysis showed ORs of GC with no significant differences between intermediate vs low and high vs low PA level (OR 1.05 [95%CI 0.76-1.45]; OR 1.23 [95%CI 0.78-1.94], respectively). GC risk estimates did not strongly differ across strata of selected covariates except for age ≤ 55 years old (high vs low level: OR 0.72 [95%CI 0.55-0.94]) and for control population-based studies (high vs low level: OR 0.79 [95%CI 0.68-0.93]).ConclusionsNo association was found between leisure time PA and GC, apart from a slight suggestion of decreased risk below age 55 and in control population-based studies. These results may reflect specific characteristics of GC at a younger age, or the presence of a cohort effect mediating and interacting with socioeconomic determinants of GC The different distribution of PA levels among hospitalized controls could have led to an underestimated effect of PA on GC risk.

Abstract Background Head and Neck Cancer (HNC) survivors are at increased risk of developing a second primary cancer (SPC). Along with the environmental risk factors, genetic factors have been associated with a potential increased susceptibility to SPC development. We aim to identify the Single Nucleotide Polymorphisms (SNPs) that contribute to SPC development among HNC survivors through a systematic review and meta-analysis. Methods We searched PubMed, Scopus and ISI Web of Science for eligible studies published in English until January 31st, 2020. We included studies reporting primary data that evaluated the association between SNPs and SPC risk in HNC patients. Data were pooled in a random-effect meta-analyses, when at least two studies on the same SNP evaluated the same genotype model. Heterogeneity was assessed using the χ2-based Q-statistics and the I2 statistics. Quality of the included studies was assessed using the Q-Genie tool. Results Twenty-one studies, of moderate to good quality, were included in the systematic review. Fifty-one genes were reported across the included studies to have significant associations with an increased SPC risk. Overall, 81 out of 122 investigated SNPs were significantly associated with the SPC risk. Seven studies were included in the meta-analysis, which showed five SNPs associated with an increased risk of SPC: p21C70T, CT + TT (HR = 1.76; 95% CI: 1.28–2.43); FASLG -844C > T, CT + TT (HR = 1.82; 95% CI: 1.35–2.46), P21 C98A, CA + AA (HR = 1.75; 95% CI: 1.28–2.38); FAS -670A > G (HR = 1.84; 95% CI: 1.28–2.66) and GST-M1, Null genotype (HR = 1.54; 95% CI: 1.13–2.10). Conclusions The identified SNPs in our systematic review and meta-analysis might serve as potential markers for identification of patients at high risk of developing SPC after primary HNC. PROSPERO Registration Number CRD42019135612 .

Abstract Background Italy was the first European country to implement a national lockdown because of the COVID-19 pandemic. Worldwide, this pandemic had a huge impact on the mental health of people in many countries causing similar reaction in terms of emotions and concerns at the population level. Our study investigated the impact of the COVID-19 pandemic on psychological well-being in a cohort of Italian university students. Methods We conducted a cross-sectional survey in the period immediately after the first lockdown through the administration of a questionnaire on the personal websites of students attending their undergraduate courses at the Università Cattolica del Sacro Cuore. We used the Patient-Health-Engagement-Scale, Self-Rating-Anxiety-Scale, and Self-Rating-Depression-Scale to assess engagement, anxiety symptoms, and depression symptoms of our sample. Results The sample size was 501 subjects, of which 35.33% were classified as anxious and 72.93% as depressed. Over 90% of respondents had good understanding of the preventive measures despite over 70% suffered from the impossibility of physically seeing friends and partners. Around 55% of students would have been willing to contribute much more to face the pandemic. An increase in the occurrences of anxiety was associated with being female, being student of the Rome campus, suffering from the impossibility of attending university, being distant from colleagues, and being unable of physically seeing one’s partner. Performing physical activity reduced this likelihood. Conclusion University students are at risk of psychological distress in the case of traumatic events. The evolution of the pandemic is uncertain and may have long-term effects on mental health. Therefore, it is crucial to study the most effective interventions to identify vulnerable subgroups and to plan for acute and long-term psychological services to control and reduce the burden of psychological problems.

Abstract Objective This study aimed to analyze the effectiveness of root‐shape inserts mounted on a reciprocating handpiece during the procedure of root surface debridement (RSD) on extracted teeth. Three different approaches were compared: ultrasonic scaling, employment of root‐shape inserts mounted on a reciprocating handpiece, and a combination of both. Materials and Methods A total of 51 extracted teeth were divided into three groups. The first group was instrumented with an ultrasonic scaler, the second group with flexible root‐shape inserts mounted on a reciprocating handpiece (grain size 40, 15, and 4 μm), whereas the final group underwent a combination of both approaches. The time required for the instrumentation was taken. The specimens were subjected to optical and scanning electron microscopy (SEM), and the photographs were evaluated by three examiners who were blinded to the study. The parameters included were: SEM roughness index (SRI) for the roughness calculation, remaining calculus Index (RCI) to evaluate the residual calculus deposits, and loss of tooth substance index (LTSI) to evaluate the loss of tooth substance caused by instrumentation. Result The results revealed that the time taken for the instrumentation was on average longer when the root‐shape inserts were employed alone, meanwhile the combined approach did not show significant difference in comparison with the ultrasonic scaling. The lower average RCI was obtained with a combined approach. The use of root‐shape inserts seems to cause a moderate increase in LTSI, especially in a combined approach, whereas it resulted in a better average SRI. Conclusion The employment of root‐shape inserts seems to be effective in the RSD for its ability to obtain a smooth and calculus‐free instrumented surface, especially when used in combination with an ultrasonic scaler, and their use can so represent a valid approach to be tested in further in vivo studies.

ObjectiveTo evaluate the effect of volume guarantee (VG) combined with high-frequency oscillatory ventilation (HFOV) on respiratory and other physiological parameters immediately after lung recruitment and surfactant administration in HFOV elective ventilated extremely low gestational age newborns (ELGAN) with respiratory distress syndrome (RDS).DesignObservational study.SettingTertiary neonatal intensive care unit.PatientsTwenty-two ELGANs of 25.5 ± 1.1 weeks of gestational age requiring invasive mechanical ventilation and surfactant administration for RDS during the first 6 h of life.InterventionsAll infants intubated in delivery room, were managed with elective HFOV and received surfactant after a lung recruitment manoeuver. Eleven infants received HFOV + VG and were compared with a control group of 11 infants receiving HFOV alone. HFOV was delivered in both groups by Dräger Babylog VN500 ventilator (Dräger, Lubeck, Germany).Main Outcome MeasuresVariations and fluctuations of delivered high-frequency tidal volume (VThf), fluctuation of pressure amplitude (ΔP) and partial pressure of CO2 (pCO2) levels after recruitment manoeuver and immediately after surfactant administration, in HFOV + VG vs. HFOV ventilated infants.ResultsThere were no significant differences in the two groups at starting ventilation with or without VG. The mean applied VThf per kg was 1.7 ± 0.3 ml/kg in the HFOV group and 1.7 ± 0.1 ml/kg in the HFOV + VG group. Thirty minutes after surfactant administration, HFOV group had a significant higher VThf/Kg than HFOV + VG (2.1 ± 0.3 vs. 1.6 ± 0.1 ml/kg, p < 0.0001) with significantly lower pCO2 levels (43.1 ± 3.8 vs. 46.8 ± 1.5 mmHg, p = 0.01), 54.4% of patients having pCO2 below 45 mmHg. Measured post-surfactant ΔP values were higher in HFOV group (17 ± 3 cmH2O) than in HFOV + VG group (13 ± 3 cmH2O, p = 0.01).ConclusionHFOV + VG maintains pCO2 levels within target range and reduces VThf delivered variations more consistently than HFOV alone after surfactant administration.

At the onset of the SARS-CoV-2 pandemic, individual and social measures were strengthened through restrictive non-pharmaceutical interventions, labelled with the term “lockdown”. In Italy, there were two lockdowns (9 March 2020–3 May 2020 and 3 November 2020–27 March 2021). As part of preventive measures, healthcare workers and the administrative staff population of Policlinico A. Gemelli underwent nasopharyngeal swab tests from 1 March 2020 to 9 February 2022, a long time interval that includes the two aforementioned lockdowns. The population included 8958 people from 1 March 2020 to 31 December 2020; 8981 people from 1 January 2021 to 31 December 2021; and 8981 people from 1 January 2022 to 9 February 2022. We then analysed pseudo-anonymized data, using a retrospective observational approach to evaluate the impact of the lockdown on the incidence of SARS-CoV-2 infections within the population. Given the 14 day contagious period, the swab positivity rate (SPR) among the staff decreased significantly at the end of the first lockdown, every day prior to 18 May 2020, by 0.093 (p < 0.0001, CI = (−0.138–−0.047)). After the fourteenth day post the end of the first lockdown (18 May 2020), the SPR increased daily at a rate of 0.024 (p < 0.0001, 95% CI = (0.013–0.034)). In addition, the SPR appeared to increase significantly every day prior to 17 November 2020 by 0.024 (p < 0.0001, CI = (0.013–0.034)). After the fourteenth day post the start of the second lockdown (17 November 2020), the SPR decreased daily at a rate of 0.039 (p < 0.0001, 95% CI = (−0.050–−0.027)). These data demonstrate that, in our Institution, the lockdowns helped to both protect healthcare workers and maintain adequate standards of care for COVID and non-COVID patients for the duration of the state of emergency in Italy.

The objectives of the study were to calculate the standardised mortality rates (SMRs) for COVID-19 in European Union/European Economic Area countries plus the UK and Switzerland and to evaluate the correlation between SMRs and selected indicators in the first versus the subsequent waves until 23 June 2021. We used indirect standardisation (using Italy as the reference) to compute SMRs and considered 16 indicators of health and social well-being, health system capacity and COVID-19 response. The highest SMRs were in Belgium, the UK and Spain in the first wave (1.20–1.84) and in Hungary, Czechia and Slovakia in the subsequent waves (2.50–2.69). Human Development Index (HDI), life expectancy, urbanisation and healthcare expenditure had positive correlations with SMR in the first wave (rho=0.30–0.46), but negative correlations (rho=−0.67 to −0.47) in the subsequent waves. Retail/recreation mobility and transit mobility were negatively correlated with SMR in the first wave, while transit mobility was inversely correlated with SMR in the subsequent waves. The first wave hit most hard countries with high HDI, high life expectancy, high urbanisation, high health expenditures and high tourism. This pattern may reflect higher early community seeding and circulation of the virus. Conversely, in the subsequent waves, this pattern was completely inversed: countries with more resources and better health status did better than eastern European countries. While major SMR differences existed across countries in the first wave, these differences largely dissipated by 23 June 2021, with few exceptions.

Introduction Precision health requires citizens that are empowered to orient health decisions towards their personal values, aware of the benefits and risks, and committed to sharing their personal data to trustful institutions. Effective citizen engagement initiatives are fundamental for the success of a precision health approach.Objective To provide an overview of citizen engagement initiatives in precision health in European Union (EU) member states.Design Scoping review.Methods The electronic databases PubMed, Web of Science, CINAHL and Embase were searched to include articles published in English. Furthermore, desk research was conducted in English, Dutch, French, Italian and Spanish. Articles or reports regarding ongoing initiatives of citizen engagement in precision health conducted in EU member states and published from January 2015 to July 2020 were considered eligible. A quality assessment of the retrieved entries using Critical Appraisal Skills Programme tool was conducted.Results We identified nine documents, which reported eight ongoing citizen engagement initiatives, with substantial variability. Government agencies, non-governmental organisations and scientific societies were the main organisers and funders. Most of the initiatives were conducted in the UK. Genomics was the most emphasised aspect of precision health in these initiatives. Among the identified initiatives, both in-person and digital means were reported.Conclusion Our work provides an overview of current citizen engagement initiatives in the EU that can be useful for stakeholders interested in designing and developing precision health projects enriched by meaningful citizen participation.PROSPERO registration number CRD42020193866.

Abstract Background We aimed to survey Delivery Room and Neonatal Intensive Care Unit (NICU) respiratory strategies dedicated to the extremely low gestational age newborn (ELGAN – GA

Severe Acquired Brain Injury (sABI) is a leading cause of disability and requires intensive rehabilitation treatment. Discharge from the rehabilitation ward is a key moment in patient management. Delays in patient discharge can adversely affect hospital productivity and increase healthcare costs. The discharge should be structured from the hospital admission toward the most appropriate environment. The purpose of our study is to investigate early predictors of outcome for discharge in older adults with sABI. A retrospective study was performed on 22 patients who were admitted to an intensive neurorehabilitation unit between June 2019 and December 2021. Patients were divided into two outcome categories, good outcome (GO) or poor outcome (PO), based on discharge destination, and the possible prognostic factors were analyzed at one and two months after admission. Among the factors analyzed, changes in the Disability Rating Scale (DRS) and Level of Cognitive Functioning (LCF) at the first and second month of hospitalization were predictive of GO at discharge (DRS, p = 0.025; LCF, p = 0.011). The presence of percutaneous endoscopic gastrostomy at two months after admission was also significantly associated with PO (p = 0.038). High Body Mass Index (BMI) and the presence of sepsis at one month after admission were possible predictors of PO (BMI p = 0.048; sepsis p = 0.014). An analysis of dynamic predictors could be useful to guarantee an early evaluation of hospital discharge in frail patients with sABI.

Lynch syndrome (LS) is an autosomal dominant condition caused by pathogenic variants in mismatch repair (MMR) genes that predispose individuals to different malignancies, such as colorectal cancer (CRC) and endometrial cancer. Current guidelines recommended testing for LS in individuals with newly diagnosed CRC to reduce cancer morbidity and mortality in relatives. Economic evaluations in support of such approach, however, are not available in Italy. We developed a decision-analytic model to analyze the cost-effectiveness of LS screening from the perspective of the Italian National Health System. Three testing strategies: the sequencing of all MMR genes without prior tumor analysis (Strategy 1), a sequential IHC and MS-MLPA analysis (Strategy 2), and an age-targeted strategy with a revised Bethesda criteria assessment before IHC and methylation-specific MLPA for patients ≥ than 70 years old (Strategy 3) were analyzed and compared to the "no testing" strategy. Quality Adjusted Life Years (QALYs) in relatives after colonoscopy, aspirin prophylaxis and an intensive gynecological surveillance were estimated through a Markov model. Assuming a CRC incidence rate of 0.09% and a share of patients affected by LS equal to 2.81%, the number of detected pathogenic variants among CRC cases ranges, in a given year, between 910 and 1167 depending on the testing strategy employed. The testing strategies investigated, provided one-time to the entire eligible population (CRC patients), were associated with an overall cost ranging between €1,753,059.93-€10,388,000.00. The incremental cost-effectiveness ratios of the Markov model ranged from €941.24 /QALY to €1,681.93 /QALY, thus supporting that "universal testing" versus "no testing" is cost-effective, but not necessarily in comparison with age-targeted strategies. This is the first economic evaluation on different testing strategies for LS in Italy. The results might support the introduction of cost-effective recommendations for LS screening in Italy.

Background and objectivesA summary indicator for evaluating the breast cancer network has never been measured at the regional level. The aim is to design treemaps providing a summary description of hospitals (including breast units) and Local Health Units (LHUs) in terms of their levels of performance within the breast cancer network of the Lazio region (central Italy). The treemap structure has an intuitive design and displays information from both general and specific analyses.MethodsPatients admitted to the regional hospitals for malignant breast cancer (MBC) surgery in 2010-2017 were selected in a population-based cohort study. These quality indicators were calculated based on the international guidelines (EUSOMA, ESMO) to assess the performance in terms of volume of activity, surgery procedure, post-surgery assistance and timeliness of medical therapy or radiotherapy beginning. The quality indicators were calculated using administrative health data systematically collected at the regional level and were included in the treemap to represent the surgery or the post-surgery areas of the breast cancer clinical pathway. In order to allow aggregation of scores for different indicators belonging to the same clinical area, up to five evaluation classes were defined using the "Jenks Natural Breaks" algorithm. A score and a colour were assigned to each clinical area based on the ranking of the indicators involved. The analyses were performed on an annual basis, by the LHU of residence and by the hospital which performed the surgical intervention.ResultsIn 2017, 6218 surgical interventions for MBC were performed in the hospitals of Lazio. The results showed a continuous increase of the level of performance over the years. Hospitals showed higher variability in the levels of performance than the LHUs. 36% of the evaluated hospitals reached a high level of performance. An audit of the S. Filippo Neri breast unit revealed incorrect coding of the input data. For this reason, the score for the indicator for the volume of wards was re-calculated and re-evaluated, with a subsequent improvement of the level of performance. Most LHUs achieved at least an average overall level of performance, with 20% of the LHUs reaching a high level of performance.ConclusionsThis is the first attempt to apply the treemap logic to a single clinical network, in order to obtain a summary indicator for the evaluation of the breast cancer care network. Our results supply decision makers with a transparent instrument of governance for heterogeneous users, directing efforts improving and promoting equity of care. The treemaps could be reproduced and adapted for other local contexts, in order to limit inappropriateness and ensure uniform levels of breast cancer care within local areas. The next step is the evaluation of audit and feedback interventions to improve the quality of care and to guarantee homogeneous levels of care throughout the region.

Background: Due to its high incidence, evaluating performance of care delivered to breast cancer patients is a crucial issue. The multidisciplinary panel E.Pic.A. (Economic Appropriateness of an Integrated Care Pathway) defined a set of key performance indicators (KPIs) to evaluate economic waste in breast cancer healthcare interventions. Methods: The E.Pic.A. panel identified the principal KPIs that are crucial within the breast cancer care pathway to evaluate the performance of care. KPIs were defined taking into account their reliability, validity, usability and feasibility of measurement through the linkage between multiple routine healthcare data sources. Results: Seven KPIs were identified: three on instrumental diagnostics, two on surgery and two on treatment. The three KPIs regarding instrumental diagnostics are aimed at assessing the inappropriateness of diagnostic tests performed before and after the index surgery. The two KPIs regarding surgery measure the inappropriateness of possible repeated interventions considering the time elapsed from the index surgery. The two KPIs regarding oncologic therapy measure the inappropriateness about the administration time of adjuvant therapy and radiotherapy considering the time elapsed from the index surgery. Conclusion: E.Pic.A methodology could help to evaluate economic waste in healthcare interventions with the objective of redirecting resources to interventions with greater value. (HTA & Market Access)

Flu vaccination for the general population, and specifically for vulnerable subgroups, brings the potential to reduce the impact of the COVID-19 pandemic in terms of mobility, mortality, and hospitalizations. In Italy, flu vaccination is recommended to all ≥6 months of age, even if it is only free of charge for specific categories. We investigated the intentions towards flu and COVID-19 vaccinations from a sample of 436 Italian university students. Results of a web-based survey show that 77.52% of them were willing to get the flu vaccine and 94.73% were willing to be vaccinated against COVID-19 when available. We identified positive predictive factors to undertake flu vaccination as being a medical student, having undertaken a previous vaccination against flu, and having a high level of concern and perceived vulnerability to the COVID-19 pandemic. Reinforced public health activities might consider engaging university students a as possible “positive influencer” towards flu and COVID-19 vaccination programs.

Objective To evaluate if weaning from high-frequency oscillatory ventilation (HFOV) directly to a non-invasive mode of respiratory support is feasible and results in successful extubation in extremely low birth weight (ELBW) infants.Design Prospective observational study.Setting Tertiary neonatal intensive care unit.Patients One hundred and eight ELBW infants of 26.2±1.4 weeks of gestational age (GA) directly extubated from HFOV.Interventions All infants were managed with elective HFOV and received surfactant after a recruitment HFOV manoeuvre. Extubation was attempted at mean airways pressure (MAP) ≤6 cm H2O with FiO2 ≤0.25. After extubation, all infants were supported by nasal continuous positive airway pressure (6–8 cm H2O).Main outcome measures Extubation failure (clinical deterioration requiring reintubation) was defined as shorter than 7 days.Results Ninety patients (83%) were successfully extubated and 18 (17%) required reintubation. No significant differences were found between the two groups in terms of birth weight, day of life and weight at the time of extubation. Multivariable analysis showed that GA (OR 1.71; 95% CI 1.04, 2.08) and higher MAP prior to surfactant (OR 1.51; 95% CI 1.06, 2.15) were associated with successful extubation.Conclusions In ELBW infants, direct extubation from HFOV at MAP ≤6 cm H2O with FiO2 ≤0.25 is feasible. Our extubation success rate (83%) is higher than conventional mechanical ventilation in this very vulnerable class of infants.

BackgroundLynch syndrome (LS) is the most common hereditary colon cancer syndrome, accounting for 3–5% of colorectal cancer (CRC) cases, and it is associated with the development of other cancers. Early detection of individuals with LS is relevant, since they can take advantage of life-saving intensive care surveillance. The debate regarding the best screening policy, however, is far from being concluded. This prompted us to conduct a systematic review of the existing screening pathways for LS.MethodsWe performed a systematic search of MEDLINE, ISI Web of Science, and SCOPUS online databases for the existing screening pathways for LS. The eligibility criteria for inclusion in this review required that the studies evaluated a structured and permanent screening pathway for the identification of LS carriers. The effectiveness of the pathways was analyzed in terms of LS detection rate.ResultsWe identified five eligible studies. All the LS screening pathways started from CRC cases, of which three followed a universal screening approach. Concerning the laboratory procedures, the pathways used immunohistochemistry and/or microsatellite instability testing. If the responses of the tests indicated a risk for LS, the genetic counseling, performed by a geneticist or a genetic counselor, was mandatory to undergo DNA genetic testing. The overall LS detection rate ranged from 0 to 5.2%.ConclusionThis systematic review reported different existing pathways for the identification of LS patients. Although current clinical guidelines suggest to test all the CRC cases to identify LS cases, the actual implementation of pathways for LS identification has not been realized. Large-scale screening programs for LS have the potential to reduce morbidity and mortality for CRC, but coordinated efforts in educating all key stakeholders and addressing public needs are still required.

INTRODUCTION:Along with the proliferation of Open Access (OA) publishing, the interest for comparing the scientific quality of studies published in OA journals versus subscription journals has also increased. With our study we aimed to compare the methodological quality and the quality of reporting of primary epidemiological studies and systematic reviews and meta-analyses published in OA and non-OA journals. METHODS:In order to identify the studies to appraise, we listed all OA and non-OA journals which published in 2013 at least one primary epidemiologic study (case-control or cohort study design), and at least one systematic review or meta-analysis in the field of oncology. For the appraisal, we picked up the first studies published in 2013 with case-control or cohort study design from OA journals (Group A; n = 12), and in the same time period from non-OA journals (Group B; n = 26); the first systematic reviews and meta-analyses published in 2013 from OA journals (Group C; n = 15), and in the same time period from non-OA journals (Group D; n = 32). We evaluated the methodological quality of studies by assessing the compliance of case-control and cohort studies to Newcastle and Ottawa Scale (NOS) scale, and the compliance of systematic reviews and meta-analyses to Assessment of Multiple Systematic Reviews (AMSTAR) scale. The quality of reporting was assessed considering the adherence of case-control and cohort studies to STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist, and the adherence of systematic reviews and meta-analyses to Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) checklist. RESULTS:Among case-control and cohort studies published in OA and non-OA journals, we did not observe significant differences in the median value of NOS score (Group A: 7 (IQR 7-8) versus Group B: 8 (7-9); p = 0.5) and in the adherence to STROBE checklist (Group A, 75% versus Group B, 80%; p = 0.1). The results did not change after adjustment for impact factor. The compliance with AMSTAR and adherence to PRISMA checklist were comparable between systematic reviews and meta-analyses published in OA and non-OA journals (Group C, 46.0% versus Group D, 55.0%; p = 0.06), (Group C, 72.0% versus Group D, 76.0%; p = 0.1), respectively). CONCLUSION:The epidemiological studies published in OA journals in the field of oncology approach the same methodological quality and quality of reporting as studies published in non-OA journals.

The human leukocyte antigen (HLA) complex on chromosome 6p21 has been unambiguously associated with multiple sclerosis (MS). The complex features of the HLA region, especially its high genic content, extreme polymorphism, and extensive linkage disequilibrium, has prevented to resolve the nature of HLA association in MS. We performed a family based association study on the isolated population of the Nuoro province (Sardinia) to clarify the role of HLA genes in MS. The main stage of our study involved an analysis of the ancestral haplotypes A2Cw7B58DR2DQ1 and A30Cw5B18DR3DQ2. On the basis of a multiplicative model, the effect of the first haplotype is protective with an odds ratio (OR) = 0.27 (95% confidence interval CI 0.13-0.57), while that of the second is deleterious, OR 1.78 (95% CI 1.26-2.50). We found both class I (A, Cw, B) and class II (DR, DQ) loci to have an effect on MS susceptibility, but we saw that they act independently from each other. We also performed an exploratory analysis on a set of 796 SNPs in the same HLA region. Our study supports the claim that Class I and Class II loci act independently on MS susceptibility and this has a biological explanation. Also, the analysis of SNPs suggests that there are other HLA genes involved in MS, but replication is needed. This opens up new perspective on the study of MS.

Multiple genome screens have been performed to identify regions in linkage or association with Multiple Sclerosis (MS, OMIM 126200), but little overlap has been found among them. This may be, in part, due to a low statistical power to detect small genetic effects and to genetic heterogeneity within and among the studied populations. Motivated by these considerations, we studied a very special population, namely that of Nuoro, Sardinia, Italy. This is an isolated, old, and genetically homogeneous population with high prevalence of MS. Our study sample includes both nuclear families and unrelated cases and controls. A multi-stage study design was adopted. In the first stage, microsatellites were typed in the 17q11.2 region, previously independently found to be in linkage with MS. One significant association was found at microsatellite D17S798. Next, a bioinformatic screening of the region surrounding this marker highlighted an interesting candidate MS susceptibility gene: the Amiloride-sensitive Cation Channel Neuronal 1 (ACCN1) gene. In the second stage of the study, we resequenced the exons and the 3' untranslated (UTR) region of ACCN1, and investigated the MS association of Single Nucleotide Polymorphisms (SNPs) identified in that region. For this purpose, we developed a method of analysis where complete, phase-solved, posterior-weighted haplotype assignments are imputed for each study individual from incomplete, multi-locus, genotyping data. The imputed assignments provide an input to a number of proposed procedures for testing association at a microsatellite level or of a sequence of SNPs. These include a Mantel-Haenszel type test based on expected frequencies of pseudocase/pseudocontrol haplotypes, as well as permutation based tests, including a combination of permutation and weighted logistic regression analysis. Application of these methods allowed us to find a significant association between MS and the SNP rs28936 located in the 3' UTR segment of ACCN1 with p = 0.0004 (p = 0.002, after adjusting for multiple testing). This result is in tune with several recent experimental findings which suggest that ACCN1 may play an important role in the pathogenesis of MS.