EASY-NET Program: Effectiveness of an Audit and Feedback Intervention in the Emergency Care for Acute Conditions in the Lazio Region.

The EASY-NET network program (NET-2016-02364191)-effectiveness of audit and feedback (A&F) strategies to improve health practice and equity in various clinical and organizational settings), piloted a novel and more structured A&F strategy. This study compared the effectiveness of the novel strategy against the sole periodic dissemination of indicators in enhancing the appropriateness and timeliness of emergency health interventions for patients diagnosed with acute myocardial infarction (AMI) and ischemic stroke in the Lazio Region. The efficacy of the intervention was assessed through a prospective quasi-experimental design employing a pre- and post-intervention (2021-2022) comparison with a control group. Participating hospitals in the Lazio Region, where professional teams voluntarily engaged in the intervention, constituted the exposed group, while the control group exclusively engaged in routine reporting activities. Effectiveness analysis was conducted at the patient level, utilizing regional health information systems to compute process and outcome indicators. The effectiveness of the intervention was evaluated using difference-in-difference models, comparing pre- and post-intervention periods between exposed and control groups. Estimates were calculated in terms of the difference in percentage points (PP) between absolute risks. Sixteen facilities for the AMI pathway and thirteen for the stroke pathway participated in the intervention. The intervention yielded a reduction in the proportion of 30-day readmissions following hospitalization for ischemic stroke by 0.54 pp in the exposed patients demonstrating a significant difference of -3.80 pp (95% CI: -6.57; -1.03; 5453 patients, 63.7% cases) in the exposed group compared to controls. However, no statistically significant differences attributable to the implemented A&F intervention were observed in other indicators considered. These results represent the first evidence in Italy of the impact of A&F interventions in an emergency setting, utilizing aggregated data from hospitals involved in the Lazio Region's emergency network.

[A&F: obstacles to implementing interventions in the health system.] / A&F: gli ostacoli nell'implementare interventi nel sistema sanitario.

Understanding how well a clinician or health care team is performing provides an essential foundation for improvement. If done well, Audit and Feedback (A&F) provides data in non-judgemental, motivating insights and leads to changes in clinical processes that benefit patients. This article will explore obstacles to optimizing the potential positive effects of A&F to improve patient care and outcomes by examining three interrelated steps in the process: the audit; the feedback; and the action. The audit requires data that will be perceived as both valid and actionable. Acquiring and using such data properly often requires partnerships. Feedback recipients need to know how to turn data into action. The A&F, therefore, should include components that direct the recipient toward feasible next steps to undertake the change that will lead to improvement. The proposed actions may be individual (learning new diagnostic or therapeutic strategies, trying a more patient-centered approach, etc.) or organizational (more proactive approaches often including the involvement of additional team members). The ability to turn feedback into action will depend on the culture of the recipient-group, and its level of experience with these change processes. Feedback facilitation or coaching may be useful for some groups or certain kinds of desired changes in practice. Inadequate leadership and support for health professionals, as they try to respond to A&F, is also often a barrier. Finally, with the final focus on the challenges of the individual Work Packages (WP) within the Easy-Net network program, the article focuses on what were the facilitating and hindering factors, the obstacles encountered, and the resistance to change overcome, useful considerations in support of the increasingly widespread implementation of A&F activities in our Healthcare System in the future.

Lymph node staging with 68Ga-PSMA PET in patients with intermediate and high-risk prostate cancer suitable for radical prostatectomy managed in a prostate cancer unit.

BACKGROUND: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is coming up as a superior imaging tool for prostate cancer (PCa). However, its use in primary staging is still debated. The aim of this study was to assess accuracy of 68Ga-PSMA PET/CT in staging patients with intermediate and high risk PCa candidates to radical prostatectomy managed in the Prostate Cancer Unit of our institution. METHODS: We retrospectively evaluated patients with biopsy-proven PCa staged through PSMA PET/CT before undergoing radical prostatectomy (RP) with extended pelvic lymph node dissection (ePLND). PET findings were categorized with respect to primary tumor (T), nodal (N) and distant metastasis (M). We analyzed the correspondence between PSMA PET/CT and final histopathological examination. RESULTS: We evaluated 42 men with high and intermediate risk PCa submitted to RP with ePLND. Mean age was 65.5 years (range, 49-76 years) and median preoperative prostate-specific antigen (PSA) was 13 ng/mL (IQR, 8.1-20 ng/mL). Patients in the high-risk group were 23 (54.7%), and the remainders were in the intermediate risk group. The mean risk of lymph node involvement (LNI) using the Memorial Sloan Kettering Cancer Center (MSKCC)-nomogram was 20%. The most common International Society of Urological Pathology (ISUP) grade was 3 (26.19%) after prostate biopsy. PSMA PET/CT showed focal prostatic uptake in 28 patients [mean value of maximum standardized uptake value (SUVmax) 18.5] and detected pelvic lymph node metastases in 6 cases (14.3%) with a median value of SUVmax 4.5 (IQR, 2-6.9). Histopathological examination detected lymph node metastases in seven patients (16.6%). In the only patient with negative PSMA PET/CT pathology revealed the presence of micrometastasis. After histopathological confirmation, sensitivity, specificity, positive and negative predictive values of pre-operative 68Ga-PSMA PET/CT were 85.7%, 100%, 100% and 97%, respectively. CONCLUSIONS: In our series, 68Ga-PSMA PET/CT holds high overall diagnostic value for lymph node staging in patients with intermediate and high risk PCa. Accuracy may depend on lymph node size.

EASY-NET Program: Methods and Preliminary Results of an Audit and Feedback Intervention in the Emergency Care for Acute Myocardial Infarction in the Lazio Region, Italy.

Within the EASY-NET network program (NET-2016-02364191), Work Package 1 Lazio evaluates the effectiveness of a structured audit and feedback (A&F) intervention compared with the web-based regional periodic publication of indicators in improving the appropriateness and timeliness of emergency healthcare for acute myocardial infarction (AMI). This work describes the A&F methodology and presents the results of the first feedback delivered. The intervention involves sending periodic reports via e-mail to participating hospitals. The feedback reports include a set of volume and quality (process and outcome) indicators, calculated by facility through the health information system of the Lazio Region and compared with regional mean, target values and values calculated for hospitals with similar volumes of activity. Health managers and clinicians of each participating hospital represent the "feedback recipients". They are invited to organize clinical and organizational audit meetings to identify possible critical issues in the care pathway and define, where necessary, improvement actions. A total of 16 facilities are involved. Twelve facilities present high volumes in all volume indicators, while three facilities present low volumes for each indicator. Concerning the quality indicators, four facilities do not present critical indicators or had average results, three facilities do not present critical indicators but show average results in at least one of the indicators and six facilities present a critical value for at least one of the indicators. The first report highlighted some critical issues in some facilities on several indicators. During the audit meetings, each facility analyzes these issues, defining appropriate improvement actions. The outcome of these actions will be monitored through subsequent reporting to support the continuous care quality improvement process.

Developing a Questionnaire Evaluating Knowledge, Attitudes and Behaviors on Audit & Feedback among General Practitioners: A Mixed Methods Study.

BACKGROUND: Audit and Feedback (A&F) is one of the most common strategies used to improve quality in healthcare. However, there is still lack of awareness regarding the enabling factors and barriers that could influence its effectiveness. The aim of this study was to develop a questionnaire to measure the knowledge, attitudes and behaviors of general practitioners (GPs) regarding A&F. The study was performed in the context of the EASY-NET program (project code NET-2016-02364191). METHODS: The survey was developed according to two steps. Firstly, a scoping review was performed in order to map the literature on the existing similar instruments with the aim of identifying the sub-domains and possible items to include in a preliminary version of the questionnaire. In the second phase, the questionnaire was reviewed by a multidisciplinary group of experts and administrated to a convenience sample in a pilot survey. RESULTS: Ten papers were included in the scoping review. The survey target and development methodology were heterogenous among the studies. The knowledge, attitudes and behaviors domains were assessed in six, nine and seven studies, respectively. In the first step, 126 pertinent items were extracted and categorized as follows: 8 investigated knowledge, 93 investigated attitudes, and 25 investigated behaviors. Then, 2 sub-domains were identified for knowledge, 14 for attitudes and 7 for behavior. Based on these results, a first version of the survey was developed via consensus among two authors and then revised by the multidisciplinary group of experts in the field of A&F. The final version of the survey included 36 items: 8 in the knowledge domain, 19 in the attitudes domain and 9 in the behaviors domain. The results of the pilot study among 15 GPs suggested a good acceptability and item relevance and accuracy, with positive answers totaling 100% and 93.3% in the proposed questions. CONCLUSIONS: The methodology used has shown to be a good strategy for the development of the survey. The survey will be administrated before and after the implementation of an A&F intervention to assess both baseline characteristics and changes after the intervention.

[The EASY-NET research programme: background, structure, and methodology]. / Il programma di rete EASY-NET: razionale, struttura e metodologie.

This is the first contribution of a series of interventions describing the EASY-NET research program (Bando Ricerca Finalizzata 2016, funds 2014-2015; NET-2016-02364191). Here, the objective is to illustrate the background and the research question, the structure and organization, the methodologies and the expected results of the programme. The main theme is audit&feedback (A&F), a proven and widespread technique for improving the quality of health care. EASY-NET, funded by the Italian Ministry of Health and by the governments of the participating Italian Regions, starts its research activities in 2019 with the aim of evaluating the effectiveness of A&F in improving care for different clinical conditions in various organizational and legislative contexts. The research network involves seven Italian Regions, each conducting specific research activities described by as many work packages (WP): Lazio (the leading Region, coordinator of the research activities), Friuli Venezia Giulia, Piedmont, Lombardy, Emilia-Romagna, Calabria, and Sicily. The involved clinical areas include the management of chronic diseases, emergency care for acute conditions, surgery in the oncological area, the treatment of heart disease, obstetrics, and the use of caesarean section and post-acute rehabilitation. The involved settings concern the community, the hospital, the emergency room, and the rehabilitation facilities. Different experimental or quasi-experimental study designs are applied in each WP to achieve specific objectives of the specific clinical and organizational context. In all WPs, the process and outcome indicators are calculated on the basis of the Health Information Systems (HIS) and, in some cases, they are integrated with measures obtained from ad hoc data collections. The programme aims to contribute to the scientific evidence on A&F also exploring the obstacles and favourable factors for its effectiveness and to promote its implementation in the health service, with the ultimate aim of improving the access to healthcare and the health outcomes for citizens.

[A&F: integrating research into practice and practice into research.] / A&F: integrare la ricerca nella pratica e la pratica nella ricerca.

This article proposes a focus on Audit & Feedback (A&F)'s sustainability. If on one side, it is essential to ask how to bring A&F interventions out of research programs into clinical practices and contexts of care. On the other, it is fundamental to ensure that the experiences gained within care contexts can inform research, helping to define the research objectives and questions whose development can support paths of change. The reflection starts from two research programs on A&F carried out in the United Kingdom, respectively, at the regional level (Aspire) in the field of primary care and at the national level (Affinitie and Enact) in the field of the transfusion system. Aspire raised awareness of the importance of establishing a primary care implementation laboratory, which randomizes practices to different types of feedback to evaluate the effectiveness, also to improve patient care. The national Affinitie and Enact programs served to 'inform' recommendations to improve the conditions for sustainable collaboration between A&F researchers and audit programs. They represent an example to understand how to incorporate research results within a national clinical audit program. Finally, starting from the complex experience of the Easy-Net research program, the reflection moves on to how it was possible to make A&F interventions sustainable in Italy beyond research projects, in clinical-care contexts in which the resources provisions make continuous and structured interventions difficult and impractical. The Easy-Net program envisages different clinical care settings, study designs, interventions, and recipients, which require different actions to adapt research results to the specific realities to which A&F's interventions are addressed.

Case Identification and Characterization of Migrants with Dementia in the Lazio Region Using Health Administrative Data.

BACKGROUND: A crucial step for planning effective public health policies for migrants with dementia is the collection of data on the local dimensions of the phenomenon and patients' characteristics. OBJECTIVE: This study aimed to identify and characterize migrants with dementia in the Lazio region using health administrative databases. METHODS: Residents with dementia aged 50 years or older, living in the Lazio region as of December 31, 2018, were identified using a validated algorithm based on hospital discharge(s), claims for antidementia drugs, and co-payment exemption for dementia. Migrants were defined as people born abroad and grouped in migrants from High Migratory Pressure Countries (HMPCs) and Highly Developed Countries (HDCs). Overall and age-specific prevalence rates were estimated in native- and foreign-born patients. RESULTS: Dementia was ascertained in 38,460 residents. Among them, 37,280 (96.9%) were born in Italy, 337 (0.9%) were migrants from HDCs, and 843 (2.2%) from HMPCs. Dementia prevalence was higher among natives (1.15%, 95% CI 1.14-1.16) relative to migrants from HDCs (0.60%, 95% CI 0.54-0.67) and HMPCs (0.29%, 95% CI 0.27-0.31). The prevalence of comorbidities did not differ between groups. Migrants with dementia had a lower likelihood of receiving antidementia treatments compared with natives (51.6% in migrants from HDCs, 49.3% in migrants from HMPCs, and 53.5% among Italians). CONCLUSION: Routinely collected data in healthcare administrative databases can support the identification of migrants with dementia. Migrants exhibited a lower age-standardized prevalence of registered dementia and lower access to dedicated treatments than Italians. These findings are suggestive of underdiagnosis and undertreatment of dementia in migrants.

SARS-CoV-2 spread and area economic disadvantage in the italian three-tier restrictions: a multilevel approach.

BACKGROUND: To face the second wave of COVID-19, Italy implemented a tiered restriction system with different limitation levels (yellow = medium; orange = medium-high, red = high) at the beginning of November 2020. The restrictions systematically reduced the transmission of SARS-CoV-2 with increasing strength for increasing tier. However, it is unknown whether the effect of limitations was equal between provinces with different socioeconomic levels. Therefore, we investigated the association between the province's socioeconomic level and SARS-CoV-2 infection daily reproduction number in each restriction level. METHODS: We measured the province's socioeconomic level as the percentage of individuals whose 2019 total yearly income was lower than 10,000€, using the measure as a proxy of economic disadvantage. We estimated the daily reproduction number (Rt) at the province level using the SARS-CoV-2 daily incidence data from November 2020 to May 2021. We then used multilevel linear regression models with random intercepts stratified by restriction level to estimate the association between economic disadvantage and Rt. We also adjusted the analyses for potential confounders of the association between the province's economic disadvantage and the Rt: the percentage of people with 0-5 years, the quartiles of population density, and the geographical repartition. RESULTS: Overall, we found increasing Rt in yellow (+ 0.004 p < 0.01, from Rt = 0.99 to 1.08 in three weeks) and containing effects for the orange (-0.005 p < 0.01, from Rt = 1.03 to 0.93) and the red tier (-0.014 p < 0.01, from Rt = 1.05 to 0.76). More economically disadvantaged provinces had higher Rt levels in every tier, although non-significantly in the yellow level (yellow = 0.001 p = 0.19; orange = 0.002 p = 0.02; red = 0.004 p < 0.01). The results showed that the association between economic disadvantage and Rt differed by level of restriction. The number of days into the restriction and the economic disadvantage had statistically significant interactions in every adjusted model. Compared to better off, more economically disadvantaged provinces had slower increasing trends in yellow and steeper Rt reductions in orange, but they showed slower Rt reductions in the highest tier. CONCLUSION: Lower tiers were more effective in more economically disadvantaged provinces, while the highest restriction level had milder effects. These results underline the importance of accounting for socioeconomic level when implementing public health measures.

[Fifteen ways to optimize feedback.] / Quindici modi per ottimizzare il feedback.

This article proposes a series of insights that are drawn from the most up-to-date scientific literature and functional for an optimal implementation of Audit & Feedback (A&F). The focus is on the "feedback" component of the methodology. Some key issues of the feedback are the capability to address changes perceived as priorities for the recipients, recommend actions that bring real improvements, and allow the people to whom recommendations are addressed to manage them. Other suggestions concern how to share the data: it is important to provide feedback as soon as possible, multiple times, starting from individual rather than general data, and including comparisons able to promote the desired change. Other operational indications concern the most effective way to display the feedback, such as tightly linking the graphical representation and the summary message, presenting the feedback in multiple ways, and simplifying the message to minimize cognitive overload. Finally, some suggestions are about how to transmit feedback: tailor interventions according to the specific barriers of a given clinical-organizational context, provide short and easily understandable messages followed by more details, emphasize the credibility of information, increase motivation to change practice, and encourage participatory feedback construction rather than passive delivery. It also proposes an analysis of some of the challenges related to the design of A&F interventions translatable into improvements in practice starting from the context of the Easy-Net network program.

Survey of Professionals of the European Public Health Association (EUPHA) towards Direct-to-Consumer Genetic Testing.

BACKGROUND: The increasing availability of Direct-to-Consumer Genetic Tests (DTC-GTs) has great implications for public health (PH) and requires literate healthcare professionals to address the challenges they pose. We designed and conducted a survey to assess the state of knowledge, attitudes and behaviours of PH professionals members of the European Public Health Association (EUPHA) towards DTC-GTs. METHODS: EUPHA members were invited to participate and fill in the survey. We performed multivariable logistic regression to evaluate associations between selected covariates and knowledge, attitudes and behaviours of healthcare professionals towards DTC-GT. RESULTS: Three hundred and two professionals completed the survey, 66.9% of whom were not involved in genetics or genomics within their professional activities. Although 74.5% of respondents were aware that DTC-GTs could be purchased on the web, most of them reported a low level of awareness towards DTC-GTs applications and regulatory aspects. The majority did not approve the provision of DTC-GTs without consultation of a healthcare professional (91.4%), were doubtful about the test utility and validity (61%) and did not feel prepared to address citizens' questions (65.6%). Predictors of knowledge on DTC-GT were the involvement in genetics/genomics and receiving training during the studies (P < 0.0001 and P = 0.043). Predictors of attitudes were medical degree and knowledge about DTC-GTs (P = 0.006 and P = 0.027). CONCLUSIONS: Our results revealed a high level of awareness of DTC-GT web purchasing and a moderate to low level of awareness towards their applications. Despite the overall positive attitudes, PH professionals reported a high need for strengthening regulatory aspects of DTC-GTs provision process.

[How to optimize Audit&Feedback: experience from the EASY-NET programme]. / Come rendere più efficace l'Audit&Feedback: riflessioni dal programma di rete EASY-NET.

This is the second of a series of papers dedicated to the EASY-NET research programme (NET-2016-02364191). The rationale, structure and methodologies are described in the previous contribution. Scientific literature demonstrated that Audit & Feedback (A&F) is an effective strategy for continuous quality improvement and its effectiveness varies considerably according to factors that are currently little known. Some recent publication pointed out, with the contribution of an international group of experts, 15 suggestions to optimize A&F and developed a tool to evaluate their application. This tool, called REFLECT-52, includes 52 items related to the 15 suggestions and organized into four categories relating to the "Nature of the desired action", to the "Nature of the data available for feedback", to the "Feedback Display" and to the "Intervention delivery". Then, the aim of this work was to evaluate the level of adherence of A&F interventions tested in EASY-NET to suggestions from the literature by using a slightly adapted version of the REFLECT-52 tool, in its original language. In EASY-NET, 14 A&F interventions with different characteristics and in different clinical and organizational contexts were tested in seven Italian regions, each of these was evaluated by the respective research groups. Overall, the level of adherence was high in three of the four categories analysed, with some difficulties reported regarding the nature of the data available for feedback. In fact, contrary to what the literature suggests, it was not possible to send repeated feedback for some interventions and, in some cases, the data available for feedback presented a delay longer than one year. In summary, this analysis has confirmed a high level of compliance of the interventions tested with the suggestions from the literature, but it has also allowed researchers to identify critical aspects that need to be addressed for the future development of these strategies.

[Audit & Feedback: how it works.] / Audit & Feedback: come funziona.

This article is the first of a series that aims to describe the Audit & Feedback (A&F) methodology. Some key elements focus on what A&F is and how it works. While it is an effective tool for promoting change in professional behaviour and improving the quality of care, there is still substantial uncertainty concerning how to implement A&F interventions to maximize its effects. The article explains how to design effective A&F on relevant issues, considering the available literature and direct experiences conducted in the National Health System (NHS). A&F interventions should aim to achieve clear, attainable, and evaluable objectives, which concern aspects of care for which there is solid evidence of literature and potential space for improvement. Based on data that measure any distance between what is expected and observed in local practice, the feedback must turn to those who can pursue the proposed change and who must trust the data collection and analysis process. Feedback should be provided more than once, in verbal and written form, and might include explicit objectives and an action plan. When planning A&F interventions, it is essential to provide specific data (e.g., aggregated at the level of a team, department, or individual doctor) rather than general, sending them directly to the professional or department involved rather than generically to the healthcare organization involved. In addition, it is essential to simplify the message so that the staff who receives the feedback can quickly understand the quality of the performance addressed and how to change it. Finally, it is necessary to encourage collaboration between the various healthcare professionals responsible for the quality of care and competence for improvement interventions (health professions, health management, quality expert personnel, and methodologists). Networking between staff improves the knowledge and effectiveness of A&F. This article finally proposes practical examples of two main aspects of A&F planning from the context of the EASY-NET program: how to increase the participation and involvement of the recipients of the intervention and the related pros and cons regarding the choice between the use of routinely available data from health information systems (SIS) and data collected ad hoc.

Escherichia coli resistance patterns, empiric and targeted antibiotic prescriptions in children: a single center experience.

BACKGROUND AND AIM: Antibiotic resistance represents one of the major public health issues, due to the potential future ineffectiveness of available antibiotics. However, epidemiological studies on E. coli antibiotic resistance patterns in the pediatric population are limited. METHODS: We conducted a retrospective analysis on children younger than 18 years of age admitted to the Department of Pediatrics from April 2016 to April 2018 with E. coli isolation on biological materials. RESULTS: 205 subjects were included in the study (mean age 1.6 years). We found an overall low rate of resistance of E. coli isolates to Amoxicil-lin/Clavulanate (20%), Cephalosporins (6.3%) and Aminoglycosides (6.3%), while no isolates were resistant to Carbapenems. Presence of invasive devices and intensive care admissions were as-sociated with resistance to Cephalosporines (P < 0.001; OR 9.21, 95% CI 2.7 - 31.39) and Amino-glycosides (P < 0.004; OR 5.42, 95% CI 1.71 - 17.15), while no factors associated with resistance to the other antibiotics were found. CONCLUSIONS: Aminoglycosides and Cephalosporins were frequently used as empiric therapy, whereas targeted therapies aimed at sparing these classes of antibiotics once antibiograms were available have not always been established. These data may inform local antimicrobial stewardship and guide the development of programs aiming at a better use of antibiotics.

Incidence and Outcomes of SARS-CoV-2 Infection in Older Adults Living with Dementia: A Population-Based Cohort Study.

BACKGROUND: The identification of risk factors for SARS-CoV-2 infection and mortality in patients with dementia is a key aspect to support clinical decisions and public health interventions. OBJECTIVE: To assess the incidence of SARS-CoV-2 infection and COVID-19 related death in a cohort of patients with dementia residing in the Lazio region and to investigate predicting factors for both infection and mortality. METHODS: This population-based study used information from administrative databases and the SARS-CoV-2 infection surveillance system. Patients with dementia (age ≥65) were enrolled as of December 31, 2019 and followed-up until February 28, 2021. Cumulative risk of infection and death within 60 days of infection onset, and age-standardized incidence (SIR) and mortality (SMR) ratios were calculated. Logistic regression models were applied to identify factors associated with infection and mortality. RESULTS: Among 37,729 dementia patients, 2,548 had a diagnosis of SARS-CoV-2 infection. The crude risk of infection was 6.7%. An increase in risk of infection was observed both in women (SIR 1.72; 95% CI 1.64-1.80) and men (SIR 1.43; 95% CI 1.33-1.54). Pneumonia, cerebrovascular and blood diseases, femur fracture, anxiety, antipsychotic and antithrombotic use were associated with an increased risk of infection. The crude risk of death was 31.0%, the SMRs 2.32 (95% CI 2.05-2.65) for men, and 2.82 (95% CI 2.55-3.11) for women. Factors associated with mortality included: male gender, age ≥85, symptoms at the diagnosis, antipsychotic and systemic antibiotics treatment. CONCLUSION: These findings emphasize the need of close and tailored monitoring of dementia patients to reduce the impact of COVID-19 on this fragile population.

Stress in Medical Students: PRIMES, an Italian, Multicenter Cross-Sectional Study.

Medical students (MSs) are healthcare workers and must also cope with education-related stressors. This study aims to assess factors associated with perceived stress in Italian MSs. A cross-sectional study was conducted in 12 Italian medical schools (MSCs) in November 2018. A questionnaire assessed socio-demographic characteristics, habits, opinions about MSC, and concerns about the future. Stress was assessed with the PSS-10. Descriptive and univariable tests were performed. A linear model was fitted to find associations of the PSS-10 score with characteristics. There were 2513 collected questionnaires. Median PSS-10 score was 18 (IQR 11). Median age was 22 (IQR 4) and 61% of the sample was female. Female gender, being part of a sexual minority, poor financial situation, competitive atmosphere, having hobbies, resting, and sleeping hindered by MSC were characteristics associated with higher PSS-10 scores. Current relationship, good family relationship, and no concerns about the future were protective factors. Being part of sexual minorities had greater effects in students not living away from home, while in the other group it was not having satisfying friendships. Medical students suffer higher levels of stress than the general population, and many MSC stressors are associated. Living away from home modifies risk and protective factors, offering the possibility to tailor group-specific interventions.

Immunosuppressive treatment and radiotherapy in kidney transplant patients: A systematic review.

BACKGROUND: Immunosuppression (IS) therapy may contribute to cancer development. Some authors have proposed to reduce immunosuppression drugs dose in case of viral infections, in immunosuppression-related diseases, and in patients undergoing radiotherapy. The present analysis reports the results of a systematic review on kidney transplant recipients undergoing immunosuppression and radiotherapy. AIM: To define if it is necessary reduce immunosuppression drugs during radiotherapy. METHODS: The literature search was based on three electronic databases (Pubmed, Scopus, and Web of Science) using selected keywords linked through the "AND" and "OR" Boolean operators to build specific strings for each electronic search engine. Two researchers independently screened the citations, and disagreement was resolved by discussion or through the intervention of a third author. The review was conducted and reported according to the PRISMA statement. Extracted data were narratively synthesized, and, where possible, frequencies, percentages, and ranges were calculated. RESULTS: The literature search resulted in 147 citations. After abstracts screening, 21 records were selected for full-text evaluation. Fifteen of these were excluded, leaving six papers considered suitable for analysis. There is still no clear evidence that withdrawing antimetabolites and/or calcineurin inhibitors and/or mammalian target of rapamycin-inhibitors, as opposed to continuing maintenance IS, improves patient survival in kidney transplant recipients with cancer undergoing radiotherapy. Only few retrospective studies on small cancer patient cohorts are available in this setting, but without comparison of different immunosuppression treatments. Even where immunosuppression therapy was described, patient survival seemed to be correlated only with cancer stage and type. CONCLUSION: The results of this systematic review do not support the reduction of immunosuppression dose in patients undergoing radiotherapy.

Circulating immune profile can predict survival of metastatic uveal melanoma patients: results of an exploratory study.

Metastatic uveal melanoma (UM) is a poor prognosis malignancy. Immunotherapy is commonly employed, despite the low activity, considering the lack of other effective systemic treatments. In this study, the prognostic and predictive role of soluble immune checkpoints and inflammatory cytokines/chemokines in 22 metastatic UM patients was evaluated. Baseline levels of these molecules were assessed, as well as their changes during anti-PD-1 therapy. The correlation between soluble immune checkpoints/cytokines/chemokines and survival was analyzed. A comparison between circulating immune profile of metastatic cutaneous melanoma (CM), for which immunotherapy is a mainstay of treatment, and UM during anti-PD-1 therapy was also performed. Three immune molecules resulted significantly higher in metastatic UM patients with survival <6 months versus patients with survival ≥6 months: IL-8, HVEM and IDO activity. Considering these three molecules, we obtained a baseline score able to predict patients' survival. The same three molecules, together with soluble(s) CD137, sGITR and sCD27, resulted significantly lower in patients with survival >30 months. We also observed an increase of sCD137, sCD28, sPD-1, sPD-L2 sLAG3, sCD80 and sTim3 during anti-PD-1 treatment, as well as IDO activity, IP-10 and CCL2. Several of these molecules were significantly higher in UM compared to CM patients during anti-PD-1 therapy. The analysis of circulating immune molecules allows to identify patients with poor prognosis despite immunotherapy and patients with long survival treated with an anti-PD-1 agent. The different serum concentration of these molecules during anti-PD-1 therapy between UM and CM reflects the different efficacy of immune checkpoint inhibitors.

Spyramicine and Trimethoprim-Sulfamethoxazole Combination to Prevent Mother-To-Fetus Transmission of Toxoplasma gondii Infection in Pregnant Women: A 28-Years Single-center Experience.

BACKGROUND: There is weak evidence on the best treatment of pregnant women with Toxoplasma gondii infection to prevent the vertical transmission to the fetus. METHODS: We conducted a 28-year retrospective study aiming to compare the efficacy of three therapeutic regimens [Spiramicyn alone (Spy) vs. Pyrimethamine-Sulfadiazine (P/S) vs. Spiramicyn with Trimethoprim-Sulfamethoxazole (Spy+TMP-SMX)] for the prevention of mother-to-fetus transmission of T. gondii infection. RESULTS: 170 women were included: 58 (34.1%) had certain congenital toxoplasmosis (CT), 61 (35.9%) a probable infection and 41 (24.1%) possible infection. In total 97 mothers (57.1%) were treated with the Spy+TMP-SMX combination, 64 mothers (37.6%) were treated with Spy only and 8 mothers (4.7%) with P/S. Infected infants were 20/170 (11.7%). However, 8.2% (8/97) of infants born to mothers treated with Spy+TMP-SMX were infected, 20% (11/55) of infants born to women treated with Spy and 12.5% (1/8) of infants born to mothers treated with P/S were infected. Logistic regression analysis demonstrated that Spy treatment alone was associated with an increased risk of CT compared to the Spy+TMP-SMX combination (OR, 2.78, 95% CI 1.04-7.41, P value 0.041). No difference was observed when the Spy+TMP-SMX was compared with the P/S combination (OR 1.59; 95% CI 0.17 - 14.58; P value 0.682). Results were confirmed when the analyses were corrected by trimester of infection and by type of maternal treatment (OR 7.72; 95% CI 3.40-17.53, P value <0.001). CONCLUSIONS: The combination of Spy+TMP-SMX may be more effective in reducing the risk of maternal-fetal transmission of Toxoplasmosis compared to Spy alone; furthermore, this combination is not inferior to P/S, the current international standard-of-care maternal treatment for the prevention of CT. A prospective trial comparing the combination Spy+TMP-SMX with P/S would be necessary to provide definitive evidence on the best regimen for pregnant women with T. gondii infection.