[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.

[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.

[Emergency department visits for interpersonal violence injuries in Udine (Friuli Venezia Giulia Region, Northern Italy)]. / Gli accessi al Pronto soccorso dell'Azienda sanitaria universitaria integrata di Udine per traumatismi causati da violenza interpersonale.

OBJECTIVES: to describe frequency, characteristics, and consequences of intentional injuries due to interpersonal violence visited at the Emergency Rooms of Udine and Cividale del Friuli (Friuli Venezia Giulia Region, North-Eastern Italy). DESIGN: analysis of the administrative database of the Emergency Department. SETTING AND PARTICIPANTS: in the two Emergency Departments of Udine and Cividale del Friuli, serving a 250,000-inhabitant area, all the visits due to injuries from interpersonal violence in the years 2015-2017 were analysed. MAIN OUTCOME MEASURES: number of visits because of injuries from interpersonal violence, distribution of demographic characteristics of patients, of characteristics of the events (place of occurrence, mechanism, relation with patient's occupation, involvement of persons known to the victims), of consequences (discharge diagnosis, Emergency Department management times). RESULTS: in three years, 1,741 visits of violence victims were recorded in the Emergency Department of the Udine area; 8.7% of patients were assigned a triage yellow tag and 1.0% a red tag. Almost one third of victims were non-Italian citizens; 14.2% of events were work-related; more than one third occurred in the home; in one third of cases, the aggressor was known to the victim; 96 people were diagnosed with fractures. The average time from start of medical care and Emergency Room discharge ranged from half an hour among white triage tags to more than three hours among yellow tags. More than 100 people experiences more than one violent episode. CONCLUSIONS: this is the first description of frequency, characteristics, and health impact of violence in the area of Udine, providing information useful for a targeted prevention. It also highlights the central role of the Emergency Department not only for the registration of the phenomenon, but also for the management of the acute episodes and for the prevention of recurrent events.

Value of the Rare Disease Registry of the Italian Region Friuli Venezia Giulia.

BACKGROUND: The lack of epidemiological and clinical data is a major obstacle in health service planning for rare diseases. Patient registries are examples of real-world data that may fill the information gap. OBJECTIVE: We describe the Rare Disease Registry of the Friuli Venezia Giulia region of Italy and its potential for research and health planning. METHODS: The Rare Disease Registry data were linked with information on mortality, hospital discharges, ambulatory care, and drug prescriptions contained in administrative databases. All information is anonymous, and data linkage was based on a stochastic key univocal for each patient. Average annual costs owing to hospitalizations, outpatient care, and medications were estimated. RESULTS: Implementation of the Registry started in 2010, and 4250 participants were registered up to 2017. A total of 2696 patients were living in the region as of January 1, 2017. The overall raw prevalence of rare diseases was 22 per 10,000 inhabitants, with higher prevalence in the pediatric population. The most common disease groups were congenital malformations, chromosomal and genetic syndromes, and circulatory and nervous diseases. In 2017, 30 patients died, 648 were hospitalized, and 2355 received some type of ambulatory care. The total annual estimated cost was approximately €6.5 million, with great variability in the average patient cost across diseases. CONCLUSIONS: The possibility of following the detailed real-world care experience of patients with each specific rare disease and assessing the costs related to each step in their care path represents a unique opportunity to identify inefficiencies, optimize care, and reduce waste of resources.

[Pharmaceutical prescription of proton pump inhibitors and ranitidine in the general population living in the area of the Healthcare Authority and University of Udine (Friuli Venezia Giulia, Northeastern Italy)]. / La prescrizione farmaceutica territoriale di inibitori di pompa protonica e ranitidina nella popolazione residente nell'area della Azienda sanitaria universitaria integrata di Udine.

OBJECTIVES: to describe the use of proton pump inhibitors (PPI) and ranitidine in the general population living in the area of the Healthcare Authority and University of Udine (Friuli Venezia Giulia, Northeastern Italy) and to evaluate whether there are any cases of co-prescription of medications in those classes. DESIGN: analysis of health-related administrative databases (list of potential healthcare beneficiaries, prescriptions of medications, exemption from medical charges because of chronic conditions, list of general practitioners). SETTING AND PARTICIPANTS: population of the Italian area of the Healthcare Authority and University of Udine (approximately 250,000 inhabitants) ≥1 year of age as of January 1st, 2016. MAIN OUTCOME MEASURES: prevalence of PPI or H2RA use (>1 prescription in 2016), overall and stratified by drug, age class and sex; duration of the theoretical period covered by prescriptions; prevalence of co-prescriptions; association of co-prescriptions and clinical and demographic characteristics of patients (odds ratio and 95% confidence intervals). RESULTS: in 2016, 162 persons per 1,000 used those medications; in particular, 158/1,000 used PPIs. Prevalence of use increased with age, as did the median treatment duration with PPIs. Co-prescription of two medications of the same class were observed in 0.43% of antacid users. The likelihood of receiving co-prescriptions was higher among non-elderly subjects, long-term PPI users, and those with chronical diseases, such asthma. CONCLUSION: in the considered Italian area, PPIs and ranitidine were frequently used, although less than in the rest of Italy. We observed occasionally non-recommended practices, such as the co-prescription of different medications of the same class or with the same indications.

Enzyme replacement and substrate reduction therapy for Gaucher disease.

BACKGROUND: Gaucher disease, a rare disorder, is caused by inherited deficiency of the enzyme glucocerebrosidase. It is unique among the ultra-orphan disorders in that four treatments are currently approved by various regulatory authorities for use in routine clinical practice. Hitherto, because of the relatively few people affected worldwide, many of whom started therapy during a prolonged period when there were essentially no alternatives to imiglucerase, these treatments have not been systematically evaluated in studies such as randomized controlled trials now considered necessary to generate the highest level of clinical evidence. OBJECTIVES: To summarize all available randomized controlled study data on the efficacy and safety of enzyme replacement therapies and substrate reduction therapy for treating Gaucher disease. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register. Additional searches were conducted on ClinicalTrials.gov for any ongoing studies with potential interim results, and through PubMed. We also searched the reference lists of relevant articles and reviews.Date of last search: 07 August 2014. SELECTION CRITERIA: All randomized and quasi-randomized controlled studies (including open-label studies and cross-over studies) assessing enzyme replacement therapy or substrate reduction therapy, or both, in all types of Gaucher disease were included. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the risk of bias in the included studies, and extracted relevant data. MAIN RESULTS: Of the 488 studies retrieved by the electronic searches, eight met the inclusion criteria and were analysed (300 participants). Response parameters were restricted to haemoglobin concentration, platelet count, spleen and liver volume and serum biomarkers (chitotriosidase and CCL18). Only one publication reported a 'low risk of bias' score in all parameters assessed, and all studies included were randomized.Four studies reported the responses to enzyme replacement therapy of previously untreated individuals with type 1 Gaucher disease. Two studies investigated maintenance enzyme replacement therapy in people with stable type 1 Gaucher disease previously treated for at least two years. One study compared substrate reduction therapy, enzyme replacement therapy and a combination thereof as maintenance therapy in people with type 1 Gaucher disease previously treated with enzyme replacement therapy. One study examined substrate reduction therapy in people with chronic neuronopathic (type 3) Gaucher disease who continued to receive enzyme replacement therapy.Treatment-naïve participants had similar increases in haemoglobin when comparing those receiving imiglucerase or alglucerase at 60 units/kg, imiglucerase or velaglucerase alfa at 60 U/kg, taliglucerase alfa at 30 units/kg or 60 units/kg, and velaglucerase alfa at 45 units/g or 60 units/kg. For platelet count response in participants with intact spleens, a benefit for imiglucerase over velaglucerase alfa at 60 units/kg was observed, mean difference -79.87 (95% confidence interval -137.57 to -22.17). There were no other significant differences in platelet count response when comparing different doses of velaglucerase alfa and of taliglucerase alfa, and when comparing imiglucerase to alglucerase. Spleen and liver volume reductions were not significantly different in any enzyme replacement therapy product or dose comparison study. Although a dose effect on serum biomarkers was not seen after nine months, a significantly greater reduction with higher dose was reported after 12 months in the velaglucerase study, mean difference 16.70 (95% confidence intervaI 1.51 to 31.89). In the two enzyme replacement therapy maintenance studies comparing infusions every two weeks and every four weeks, there were no significant differences in haemoglobin concentration, platelet count, and spleen and liver volumes over a 6 to 12 month period when participants were treated with the same cumulative dose.A total of 25 serious adverse events were reported, nearly all deemed unrelated to treatment.There are, as yet, no randomized trials of substrate reduction therapy in treatment-naïve patients that can be evaluated. Miglustat monotherapy appeared as effective as continued enzyme replacement therapy for maintenance of hematological, organ and biomarker responses in people with type 1 Gaucher disease previously treated with imiglucerase for at least two years. In those with neuronopathic Gaucher disease, no significant improvements in haemoglobin concentration, platelet count or organ volumes occurred when enzyme replacement therapy was augmented with miglustat.One randomized controlled study assessing substrate reduction therapy was published immediately prior to producing the final version of this review, and this, along with a further ongoing study (expected to be published in the near future), will be assessed for eligibility in a future update of the review. AUTHORS' CONCLUSIONS: The results reflect the limitations of analysing evidence restricted to prospective randomized controlled trials, especially when dealing with chronic rare diseases. This analysis suggests that, during the first year of treatment, different recombinant glucocerebrosidases are bio-similar and non-inferior in safety and efficacy for surrogate biological response parameters. Enzyme replacement therapy given at 30 to 45 units/kg body weight every two to four weeks was generally as effective as the 60 unit/kg dose for the assessed clinical outcomes. The analysis emphasise the need to determine whether it is realistic to carry out multi-decade prospective clinical trials for rare diseases such as type 1 Gaucher disease. With large treatment effects on the classical manifestations of the disorder, therapeutic investigations in Gaucher disease mandate innovative trial designs and methodology to secure decisive data concerning long-term efficacy and safety - with the realization that knowledge about disease-modifying actions that are sustained are of crucial importance to people with this chronic condition.

Long term effects of enzyme replacement therapy in an Italian cohort of type 3 Gaucher patients.

BACKGROUND: The chronic neuropathic form of Gaucher disease (GD3) is characterised by hepatosplenomegaly, anaemia, thrombocytopenia, bone alterations and central neurological involvement. Enzyme replacement therapy (ERT) has been demonstrated to be effective in non neuropathic Gaucher disease, but long term results in patients with GD3 are still limited and contrasting. A possible role of genotype in determining the response to ERT has been hypothesised. PATIENTS AND METHODS: All patients affected by GD3, treated with ERT, and followed-up in 4 different Italian centres (Udine, Catanzaro, Sassari and Florence) were included. Data on clinical conditions, laboratory values, neurological and neuropsychological examinations, radiological and electrophysiological features were collected retrospectively from clinical records. RESULTS: Ten patients (6 females, 4 males) with four different genotypes (L444P/L444P, L444P/F231I, P159T/unknown, C.115+1G>A/N188S) were identified. They received ERT infusions from 3 to 21years. Haematological parameters and organomegaly improved/normalised in all patients. Three patients showed severe progressive skeletal deformities. 6/10 patients were neurologically asymptomatic when they started ERT for systemic symptoms. During the follow-up, 2/6 developed an important central nervous system disease; 2/6 developed mild central symptoms; and 2/6 did not show any neurological symptom after 5, and 20years of treatment respectively, despite the presence of epileptiform abnormalities at the electroencephalogram. Overall, neurological involvement worsened over time in 6/10 patients, 3 of whom developed progressive myoclonic encephalopathy and died. CONCLUSIONS: ERT improved the systemic manifestations in patients with GD3, but was not able to counteract the progression of neurological symptoms in the long term.

Enzyme replacement therapy in juvenile glycogenosis type II: a longitudinal study.

UNLABELLED: Glycogenosis type II, a genetic muscle-wasting disorder, results in a spectrum of clinical phenotypes. Enzyme replacement therapy is effective in the infantile form of the disease, while little is known about its effectiveness in late-onset disease, especially in juvenile patients. The purpose of this retrospective cohort study was to assess the long-term effects of enzyme replacement therapy (ERT) in juvenile glycogenosis type II (GSDII). Eight Italian juvenile GSDII patients, receiving biweekly infusions of 20 mg/kg recombinant human α-glucosidase for at least 72 months, were enrolled (median age at therapy start was 11.8 years). Six-minute walk test (6MWT) and forced vital capacity (FVC), measured in upright position, were chosen as the principal outcome measures. Global motor disability (modified Walton scale (WS)), muscle enzymes levels [creatine phosphokinase (CK), lactate dehydrogenase (LDH), aspartate transaminase (AST), alanine transaminase (ALT)] and body mass index (BMI) were also analysed both at baseline (therapy start) and annually afterwards. At baseline, most patients (six out of eight) did not show muscle function impairment (WS ≤ 2). The performance at 6MWT showed a slight improvement during follow-up as well as FVC. Muscle enzymes levels showed a clear decrease after the 1st year of treatment while remained stable afterwards. An overall decrease in BMI was also observed during follow-up, although at the individual level, trends were variable. CONCLUSION: ERT is effective in stabilising both motor and lung functions in juvenile patients with GSDII, possibly slowing down the rate of disease progression. Randomised controlled trials are needed to understand whether early treatment allows juvenile patients to reach adulthood with a more beneficial residual muscular function than untreated patients.

Introducing Virtual Reality in a STEMI Coronary Syndrome Course: Qualitative Evaluation with Nurses and Doctors.

In the increasing number of medical education topics taught with virtual reality (VR), the prehospital management of ST-segment elevation myocardial infarction (STEMI) had not been considered. This article proposes an implemented VR system for STEMI training and introduces it in an institutional course addressed to emergency nurses and case manager (CM) doctors. The system comprises three different applications to, respectively, allow (a) the course instructor to control the conditions of the virtual patient, (b) the CM to communicate with the nurse in the virtual field and receive from him/her the patient's parameters and electrocardiogram, and (c) the nurse to interact with the patient in the immersive VR scenario. We enrolled 17 course participants to collect their perceptions and opinions through a semistructured interview. The thematic analysis showed the system was appreciated (n = 17) and described as engaging (n = 4), challenging (n = 5), useful to improve self-confidence (n = 4), innovative (n = 5), and promising for training courses (n = 10). Realism was also appreciated (n = 13), although with some drawbacks (e.g., oversimplification; n = 5). Overall, participants described the course as an opportunity to share opinions (n = 8) and highlight issues (n = 4) and found it useful for novices (n = 5) and, as a refresh, for experienced personnel (n = 6). Some participants suggested improvements in the scenarios' type (n = 5) and variability (n = 5). Although most participants did not report usage difficulties with the VR system (n = 13), many described the need to get familiar with it (n = 13) and the specific gestures it requires (n = 10). Three suffered from cybersickness.

Supporting Fair and Efficient Emergency Medical Services in a Large Heterogeneous Region.

Emergency Medical Services (EMS) are crucial in delivering timely and effective medical care to patients in need. However, the complex and dynamic nature of operations poses challenges for decision-making processes at strategic, tactical, and operational levels. This paper proposes an action-driven strategy for EMS management, employing a multi-objective optimizer and a simulator to evaluate potential outcomes of decisions. The approach combines historical data with dynamic simulations and multi-objective optimization techniques to inform decision-makers and improve the overall performance of the system. The research focuses on the Friuli Venezia Giulia region in north-eastern Italy. The region encompasses various landscapes and demographic situations that challenge fairness and equity in service access. Similar challenges are faced in other regions with comparable characteristics. The Decision Support System developed in this work accurately models the real-world system and provides valuable feedback and suggestions to EMS professionals, enabling them to make informed decisions and enhance the efficiency and fairness of the system.

Fertility and pregnancy in women affected by glycogen storage disease type I, results of a multicenter Italian study.

BACKGROUND: Life expectancy of patients with glycogen storage disease (GSD) type I has improved considerably, opening new problems correlated with adult age. In females polycystic ovaries (PCOs) has been described as frequently associated with the disease, however successful pregnancies have been reported. Whether or not GSD I is associated with impaired reproductive function is still unclear. PATIENTS AND METHODS: Data about female patients with GSD Ia and Ib, who were 16 years or older, were obtained from clinical records and interviews. RESULTS: A total of 32 women with GSD I (25 GSD Ia, 7 GSD Ib), median age 26 years (range 16-55), were included. 9/32 patients had delayed menarche, 17/32 had irregular cycles, 8/22 had documented polycystic ovaries. Five successful spontaneous pregnancies in four patients with GSD Ia and two in a woman with GSD Ib were reported. The latter had development and enlargement of hepatic adenomas during pregnancies. CONCLUSION: Despite the high prevalence of irregular menstruation cycles and polycystic ovaries, fertility seems not to be impaired in women with GSD I. During pregnancy monitoring for adenoma development is mandatory.

Chemotherapy prescribing errors: an observational study on the role of information technology and computerized physician order entry systems.

BACKGROUND: Chemotherapy administration is a high-risk process. Aim of this study was to evaluate the frequency, type, preventability, as well as potential and actual severity of outpatient chemotherapy prescribing errors in an Oncology Department where electronic prescribing is used. METHODS: Up to three electronic prescriptions per patient record were selected from the clinical records of consecutive patients who received cytotoxic chemotherapy between January 2007 and December 2008. Wrong prescriptions were classified as incomplete, incorrect or inappropriate. Error preventability was classified using a four-point scale. Severity was defined according to the Healthcare Failure Mode and Effect Analysis Severity Scale. RESULTS: Eight hundred and thirty-five prescriptions were eligible. The overall error rate was 20%. Excluding systematic errors (i.e. errors due to an initially faulty implementation of chemotherapy protocols into computerized dictionaries) from the analysis, the error rate decreased to 8%. Incomplete prescriptions were the majority. Most errors were deemed definitely preventable. According to error presumptive potential for damage, 72% were classified as minor; only 3% had the potential to produce major or catastrophic injury. Sixty-eight percent were classified as near misses; adverse drug events had no or little effect on clinical outcome. CONCLUSIONS: Chemotherapy prescribing errors may arise even using electronic prescribing. Although periodic audits may be useful to detect common errors and guide corrective actions, it is crucial to get the computerized physician order entry system and set-ups correct before implementation.

Comparison of seafood consumption in a group of Italian mother-child pairs.

Seafood is an important component of healthful human diets. Intake of seafood is recommended both for young women and children. In fact, it is a good source of high-quality protein, low in saturated fats, and rich in essential nutrients (e.g. iodine, iron, choline, and selenium) and long-chain polyunsaturated fatty acids (LCPUFAs), especially omega-3. However, the relationship between maternal diet and the children's dietary habits is controversial. This study investigated the possible association between the seafood consumption by mothers and that by their 8-11 years old children and compared maternal seafood intakes during pregnancy and about 10 years later. The seafood consumption by 37 pregnant women was assessed in 1999-2001. In 2009, mothers were asked to report their weekly intake and their children's. Mother-child pairs showed a similar consumption pattern: the overall intake was 1.28 +/- 0.77 versus 1.19 +/- 0.64 (p = 0.49) while the sum of specific items was 3.71 +/- 3.01 versus 3.18 +/- 2.90 (p = 0.049). However, it cannot be discerned whether maternal diet affected the children's nutritional habits or vice-versa. In fact, mothers showed to have a higher seafood intake about 10 years after pregnancy (3.71 versus 1.83; p < 0.001), suggesting that a progressive modification of dietary habits occurred after delivery, possibly due to the influence of maternal diet on the nutritional habits of offspring or due to the presence of children in the family unit, that could have influenced maternal dietary habits. This dietary improvement could be brought forward through educational interventions addressed to young women, that could also allow a more informed choice of the healthier species of fish both for them and their children.

[Interrater reliability of the Bayley III test in the Italian Northern-Adriatic Cohort II]. / Concordanza interesaminatore del test Bayley III in una coorte di bambini del Nord-Est Italia.

OBJECTIVE: to assess the agreement between two trained psychologists who administered the Bayley Scale of Infant Development III (BSID III) to detect neurodevelopment deficits in a cohort of children within the Northern Adriatic Cohort II (NAC II) longitudinal study, which aims to assess the impact of mercury exposure through food consumption of mothers in pregnancy on their children's neurodevelopment. DESIGN: a reliability study was carried out. Two trained psychologists administered the test, each one scoring the test independently, and serving as the primary examiner for half of the sample and as the observer for the other half. SETTING AND PARTICIPANTS: a sample of 53 children of 18 months of age was enrolled consecutively within the Italian NAC II, and tested using the Bayley Scale of Infant Development III (BSID III) to detect neurodevelopment deficits. MAIN OUTCOME MEASURES: the cognitive, language, and motor scales of the BSID III were evaluated and the respective Intraclass Correlation Coefficients (ICC) were calculated. RESULTS: overall, the ICCs for the cognitive and language scales were very high (≥0.98), while the ICCs for the motor scales were slightly lower, ranging from 0.86 (gross motor, scaled) to 0.97 (fine motor, scaled), but still higher than 0.80, reported as the general acceptable benchmark for psychological testing. CONCLUSION: the interrater reliability of all BSID III scales for this sample of 18-month-old children is very high and assures comparable results between the two psychologists involved in the Italian NAC II study. The reasons are a common training, the joint evaluation of many children during the preliminary phase of the study, the discussion of inconsistent results, but also the "go no-go" nature of the items in BSID III.

Vaccination against human papilloma virus in a Northeastern Italian area.

OBJECTIVES: Vaccination against human papilloma virus (HPV) in adolescents and persons at increased risk of infection and related consequences is an effective strategy to prevent genital cancers. The objective of this study was to assess vaccination activity and coverages in a Northeastern Italian area. METHODS: Anonymous data from various health administrative databases of the Italian 530,000-inhabitant Health Authority "Azienda Sanitaria Universitaria Friuli Centrale" were deterministically linked at the individual level through an anonymous stochastic key. Doses of HPV vaccine administered by year and coverages in different birth cohorts were calculated. Vaccinations of women treated for a CIN2+ lesion were also identified. RESULTS: The number of doses administered by year followed the evolution of national and regional laws. A steep drop was observed in 2020 and 2021 in both males and females (from 6,907 in 2019 to 5,027 in 2020 in males and from 6,989 in 2019 to 4,348 in 2020 in females). Coverages in adolescents were variable across Vaccination Services located in different sub-areas (complete cycle coverage in the 2008 cohort ranged from <40% in some Districts to >70% in others). Vaccination doses administered in adult women have increased almost steadily since 2018. One third of women treated for a CIN2+ were vaccinated. CONCLUSIONS: In this area, efforts must be done to catch-up with doses missed during the pandemic and to overcome differences among different sub-areas.

[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.

[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.

Exploratory predictive and prognostic factors in advanced breast cancer treated with metronomic chemotherapy.

The aim of the present study is to evaluate the clinical and biological factors (including markers of angiogenesis) as potential predictors of prognosis and benefit from metronomic therapy in patients with advanced breast cancer (ABC). Recent data suggest antiangiogenic activity of metronomic therapy. The study population included 62 patients with pretreated ABC who received cyclophosphamide and methotrexate orally. Tumour samples were analysed by immunohistochemistry for HER2, Ki-67, thymidine phosphorylase (TP), vascular endothelial growth factor and vascular endothelial growth factor receptor. The results from immunohistochemical analysis and clinico-pathological variables were studied to test their potential association with benefit from metronomic therapy. The median overall survival, progression-free survival and survival postprogression were 7.1 (range 0.2-38.3), 2.6 (range 0.2-28.9) and 3 (range 0-34.2) months, respectively. Among the clinical variables, age, performance status and previous therapy with taxanes were significantly associated with outcomes. Among the molecular markers, TP was found to be associated with progression-free survival. Metronomic therapy is an effective choice for ABC. Young women with a more indolent disease had the greatest benefit from this treatment. TP tumour expression might aid decision making but these findings must be confirmed in larger prospective, properly designed studies.

Long-term bone mineral density response to enzyme replacement therapy in a retrospective pediatric cohort of Gaucher patients.

Osteopenia is described as a relevant sign of bone involvement in Gaucher disease (GD) both in pediatric and adult patients. Furthermore, abnormal bone metabolism is considered to play a role in growth and pubertal delay. To analyze the long-term effect of enzyme replacement therapy (ERT) on bone mineral density (BMD), a retrospective observational study was conducted in a cohort of 18 GD pediatric patients (13 males, 5 females; median age 9.2 years). They received biweekly infusions of 20-60 IU/kg of alglucerase/imiglucerase. Clinical, laboratory and imaging parameters were evaluated every 2 years. According to the International Society of Clinical Densitometry guidelines, a Z-score ≤ -2.0 was considered pathological. Nine patients (group P0) began ERT during infancy and nine (group P1) during puberty. At baseline, in three patients (16.6 %; 1P0, 2P1) Z-score was ≤ -2.0 (range -2.47 to -2.25). In patient P0 it normalized after 2 years, while in the 2P1 patients (splenectomized siblings) it persisted abnormal. The remaining 15 patients (83.4 %) always presented a normal value. In group P0, Z-score improved in infancy but showed a significant decrease during puberty, on the contrary it constantly improved in group P1. Furthermore, at baseline group P0 showed a higher median Z-score than group P1: 0.79 (0.38; 1.50) and -1.61 (-2.25; -1.56) respectively. The use of correct BMD standards to interpret bone loss during pediatric age suggests a limited significance of bone loss in these patients. Moreover, the persistence of residual disease activity may affect normal bone growth during puberty in GD populations.

[Assessing the trend in the aging of the nursing staff at two hospitals of the Friuli Venezia Giulia region: application of a deterministic mathematical model]. / Stima del trend di invecchiamento della popolazione infermieristica di due ospedali del Friuli Venezia Giulia: applicazione di un modello matematico deterministico.

BACKGROUND: The aging of the nursing workforce is a phenomenon that several industrialized countries has been facing for at least a decade. In Italy, for the period between 2011 and 2021, the issue associated with the nursing workforce will not be one of shortage but rather one of aging. AIMS: The main objective of this study was to estimate the employed nurse population aging trends for the period 2009-2035 in two Teaching Hospitals (TH1 and TH2) located in the North of Italy. METHODS: A deterministic mathematical model has been developed in order to obtain aging projections for the nursing workforce from 2009 until 2035. RESULTS: Within the next six years, the aging trend of nurse populations, with respect to 2008, at the TH 1 and 2 will show a steady increase of nurses aged over 45; specifically, a 29.4% vs. 34.1% increase and a 21.6% vs. 41.4% respectively. It is hypothesized that the TH 1 will have the highest proportion of nurses aged over 45 in 2014, whereas it is estimated that for the TH 2 this trend will continue until 2021 when the proportion of nurses aged over 45 will make up 48.8% out of the nurse population. DISCUSSION: The trend may lead to an increase in the number of experienced nurses; however, such a trend should be looked at with concern, with respect to the physical unsuitability. Nurses aged over 45 represent 20% of the workforce at both TH. Conclusions/implications for management and research. If the trend predicted by the model were to occur in the coming years, the problem of nursing workforce ageing will have to be addressed because it involves different expectations but also the perception of different work skills. The nursing direction is called to test new strategies for managing the staff and the career of nurses will also need to be redesigned, because contract law looks primarily at the initial stage of working life (specializations, university education, career opportunities) neglecting the final one (from the 50th year of age to retirement).