Anisakiasis in italy: analysis of hospital discharge records in the years 2005-2015

Background Anisakiasis is a fish-borne zoonosis caused by the ingestion of marine food infected with Anisakis third-stage larvae, widespread marine parasitic nematodes. Gastrointestinal and/ or allergic clinical signs and symptoms are not specific. While frequently reported in countries with large raw fish consumption as Japan, the global prevalence of anisakiasis may be severely underestimated due to limitations of available diagnostic tools and to diverse clinical manifestations. Recently, infective larvae were found in the same localization with gastrointestinal tumors. The occurrence of allergic exacerbation upon secondary exposure and the possible occupational exposure, highlight the need to increase scientific evidences on anisakiasis. Methods We performed a retrospective descriptive study using analysis of Hospital Discharge Records (HDRs) from 2005 to 2015 in Italy, with particular attention to allergic manifestations. Descriptive statistics and multivariate analyses were performed using backward step-wise logistic regression models to assess spatial distribution and temporal trend as well as the variables independently associated with the allergic clinical signs and symptoms in Italian cases of anisakiasis. Results HDRs reporting the ICD-9 code for anisakiasis were retrieved (370), with a higher number of cases reported from central and southern regions, with particular regard to populations inhabiting the coastal territories. Around 40% of patients presented allergic manifestations and half of them showed serious allergic reactions. The multivariate analyses showed an independent association between allergic manifestations and features as living in southern regions and female gender, while anaphylactic episodes was independently associated only with female gender. Conclusion The present study is the first attempt to a better understanding of the epidemiological picture of anisakiasis in Italy, mining official data. A common strategy on data collection, monitoring and reporting would favor a more accurate epidemiological scenario in Italy, since the report of the diseases is not mandatory

Utilization of big data to improve management of the emergency departments. Results of a systematic review

Background. The emphasis on using big data is growing exponentially in several sectors including biomedicine, life sciences and scientific research, mainly due to advances in information technologies and data analysis techniques. Actually, medical sciences can rely on a large amount of biomedical information and Big Data can aggregate information around multiple scales, from the DNA to the ecosystems. Given these premises, we wondered if big data could be useful to analyze complex systems such as the Emergency Departments (EDs) to improve their management and eventually patient outcomes. Methods. We performed a systematic review of the literature to identify the studies that implemented the application of big data in EDs and to describe what have already been done and what are the expectations, issues and challenges in this field. Results. Globally, eight studies met our inclusion criteria concerning three main activities: the management of ED visits, the ED process and activities and, finally, the prediction of the outcome of ED patients. Although the results of the studies show good perspectives regarding the use of big data in the management of emergency departments, there are still some issues that make their use still difficult. Most of the predictive models and algorithms have been applied only in retrospective studies, not considering the challenge and the costs of a real-time use of big data. Only few studies highlight the possible usefulness of the large volume of clinical data stored into electronic health records to generate evidence in real time. Conclusion. The proper use of big data in this field still requires a better management information flow to allow real-time application

Familial hypercholesterolemia: a systematic review of guidelines on genetic testing and patient management

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal-dominant hereditary disorder of lipid metabolism that causes lifelong exposure to increased LDL levels resulting in premature coronary heart disease and, if untreated, death. Recent studies have shown its prevalence to be higher than previously considered, which has important implications for the mortality and morbidity of associated cardiovascular disease (CVD). Several clinical tools are used worldwide to help physicians diagnose FH, but nevertheless most patients remain undetected. This systematic review of guidelines aims to assess the role of genetic testing in the screening, diagnosis, and management of patients affected by heterozygous or homozygous FH and to identify related health-care pathways. METHODS: We performed a systematic review of the literature; inclusion criteria were English or Italian guidelines focusing on genetic testing. The guidelines were included and evaluated for their content and development process using the Appraisal of Guidelines for Research and Evaluation II instrument. RESULTS: Ten guidelines were considered eligible, and all were judged to be of good quality, with slight differences among them. The most common indications for performing genetic tests were high levels of cholesterol, or physical findings consistent with lipid disorder, in the subject or in the family history. Subsequent screening of family members was indicated when a mutation had been identified in the index patient. Regarding patient management, the various guidelines agreed that intensive treatment with lipid-lowering medications should begin as quickly as possible and that lifestyle modifications should be an integral part of the therapy. CONCLUSION: Since the early detection of affected patients is beneficial for effective prevention of CVD, genetic testing is particularly useful for identifying family members via cascade screening and for distinguishing between heterozygous and homozygous individuals, the latter of which require more extreme therapeutic intervention

Pazienti ad alto rischio in patologia carotidea: endoarterectomia vs. trattamento endovascolare

Le procedure endovascolari, introdotte negli anni \u201970 per il trattamento a minima invasivit\ue0 di lesioni vascolari di difficile accesso o ad elevato rischio chirurgico (lesioni vascolari intracraniche, angiodisplasie, etc.), hanno avuto negli anni \u201980 e soprattutto nell\u2019ultimo decennio un\u2019evoluzione \u201cesplosiva\u201d nel trattamento di pressoch\ue9 tutte le patologie arteriose, sia di tipo ostruttivo che dilatativo,dei diversi territori vascolari (1, 2). Negli anni \u201990, per molte patologie arteriose si \ue8 verificata un\u2019inversione di tendenza e per esse \ue8 diventato approccio di prima scelta la procedura endovascolare, sostituendosi quasi completamente all\u2019intervento chirurgico o integrandosi con esso per permettere di ottenere risultati pi\uf9 duraturi nel tempo. Pertanto, negli ultimi anni, le procedure percutanee hanno avuto un rapido sviluppo e si \ue8 tentato di applicare tali metodiche a tutti gli ambiti della patologia vascolare; questo anche in considerazione del continuo e progressivo sviluppo di nuovi materiali. L\u2019applicazione delle tecniche endovascolari al distretto sovraortico, e alle arterie carotidi in particolare, \ue8 sicuramente quella che ha pi\uf9 faticato ad affermarsi, soprattutto in considerazione del rischio di embolizzazione del sistema nervoso centrale e agli ottimi risultati attualmente raggiunti dalla chirurgia carotidea (3). L\u2019ictus ischemico cerebrale rappresenta la terza causa di morte, dopo le malattie cardiovascolari e le neoplasie; si pensi che studi della letteratura riportano l\u2019ictus come responsabile del 26,3% delle morti in Giappone, del 9,4% in Italia e del 6,3% negli USA (4). La mortalit\ue0 a 30 giorni dall\u2019ictus raggiunge il 20%, mentre la sopravvivenza a 1 e a 5 anni \ue8 rispettivamente del 52% e del 30%. Fra coloro che superano un ictus 2/3 presentano deficit neurologici permanenti, la met\ue0 sopravvive per almeno 5 anni e 1/3 richiedono una riabilitazione in centri specializzati; solo il 36% ritorna ad un\u2019attivit\ue0 lavorativa e il 4% rimane non autosufficiente (5). L\u2019infarto cerebrale ischemico \ue8 responsabile di oltre l\u201980% dei casi d\u2019ictus nella popolazione, di cui solo il 16-20% \ue8 d\u2019origine cardioembolica, mentre la patogenesi della grande maggioranza di tali eventi \ue8 da ricondursi alla presenza di placche aterosclerotiche a livello dei principali vasi cerebroafferenti ed in particolare a livello della biforcazione carotidea.Non disponibil

ER access by foreign citizens between 1999 and 2014 in five large hospital of Rome, Italy

...Lack of information about the health services and the status of illegal immigrant can make difficult for foreign population to access primary care, leading to misuse of emergency rooms (ER). This study investigated the accesses between January 1999 and December 2014 to the ERs of five large hospital of Rome, Italy

Emergency Department Overcrowding. A Retrospective Spatial Analysis and the Geocoding of Accesses. A Pilot Study in Rome

The overcrowding of first aid facilities creates considerable hardship and problems which have repercussions on patients’ wellbeing, the time needed for a diagnosis, and on the quality of the assistance. The basic objective of this contribution, based on the data collected by the Hospital Policlinico Umberto I in Rome (Lazio region, Italy), is to carry out a territorial screening of the municipality using GIS applications and spatial analyses aimed at reducing—in terms of triage—code white (inappropriate) attendances, after having identified the areas of greatest provenance of improperly used emergency room access. Working in a GIS environment and using functions for geocoding, we have tested an experimental model aimed at giving a close-up geographical-sanitary look at the situation: recognizing the territorial sectors in Rome which contribute to amplifying the Policlinico Umberto I emergency room overcrowding; leading up to an improvement of the situation; promoting greater awareness and knowledge of the services available on the territory, a closer relationship between patient and regular doctor (general practitioner, GP) or Local Healthcare Unit and a more efficient functioning of the emergency room. In particular, we have elaborated a “source” map from which derive all the others and it is a dot map on which all the codes white have been geolocalized on a satellite image through geocoding. We have produced three sets made up of three digital cartographic elaborations each, constructed on the census sections, the census areas and the sub-municipal areas, according to data aggregation, for absolute and relative values, and using different templates. Finally, following the same methodology and steps, we elaborated another dot map about all the codes red to provide another kind of information and input for social utility. In the near future, this system could be tested on a platform that spatially analyzes the emergency department (ED) accesses in near-real-time in order to facilitate the identification of critical territorial issues and intervene in a shorter time to regulate the influx of patients to the ED

Are community-based nurse-led self-management support interventions effective in chronic patients? Results of a systematic review and meta-analysis

The expansion of primary care and community-based service delivery systems is intended to meet emerging needs, reduce the costs of hospital-based ambulatory care and prevent avoidable hospital use by the provision of more appropriate care. Great emphasis has been placed on the role of self-management in the complex process of care of patient with long-term conditions. Several studies have determined that nurses, among the health professionals, are more recommended to promote health and deliver preventive programs within the primary care context. The aim of this systematic review and meta-analysis is to assess the efficacy of the nurse-led self-management support versus usual care evaluating patient outcomes in chronic care community programs. Systematic review was carried out in MEDLINE, CINAHL, Scopus and Web of Science including RCTs of nurse-led self-management support interventions performed to improve observer reported outcomes (OROs) and patients reported outcomes (PROs), with any method of communication exchange or education in a community setting on patients >18 years of age with a diagnosis of chronic diseases or multi-morbidity. Of the 7,279 papers initially retrieved, 29 met the inclusion criteria. Meta-analyses on systolic (SBP) and diastolic (DBP) blood pressure reduction (10 studies-3,881 patients) and HbA1c reduction (7 studies-2,669 patients) were carried-out. The pooled MD were: SBP -3.04 (95% CI -5.01--1.06), DBP -1.42 (95% CI -1.42--0.49) and HbA1c -0.15 (95% CI -0.32-0.01) in favor of the experimental groups. Meta-analyses of subgroups showed, among others, a statistically significant effect if the interventions were delivered to patients with diabetes (SBP) or CVD (DBP), if the nurses were specifically trained, if the studies had a sample size higher than 200 patients and if the allocation concealment was not clearly defined. Effects on other OROs and PROs as well as quality of life remain inconclusive

690. Permanent Epigenetic Silencing of Human Genes With Artificial Transcriptional Repressors

There are several diseases whereby the goal of gene therapy is to silence rather than replace a gene function. Paradigmatic examples are diseases caused by a dominant negative mutation or those in which silencing of a host gene confers resistance to a pathogen or compensates the function of the missing gene. Yet, gene silencing can be used to enhance efficacy of cell therapy and for biotechnological applications. Until now, two technologies have been used to silence gene expression, namely RNA interference with short harping RNAs (shRNA) and gene disruption with Artificial Nucleases (ANs). Although some promising pre-clinical and clinical data have been already obtained, the low efficiency of knock-down with shRNA and of biallelic disruption with ANs may limit efficacy of these treatments, especially when residual gene activity can exert a biological function. To overcome this issue, we have developed a novel modality of gene silencing that exploits endogenous epigenetic mechanisms to convey robust and heritable states of repression at the desired target gene. We have generated Artificial Transcriptional Repressors (ATRs), chimeric proteins containing a custom-made DNA binding domain fused to the effector domain of a chromatinmodifying enzyme involved in silencing of Endogenous RetroViruses (ERVs). By performing iterative rounds of selection in human cell lines and primary cells engineered to report for synergistic activity of candidate effector domains, we identified a combination of 3 domains that, when transiently co-assembled on the promoter of the reporter cassette, fully abrogated transgene expression in up to 90% of treated cells. Importantly, silencing was maintained for more than 250 days in cultured cell lines, was resistant to in vitro differentiation or metabolic activation of primary cells, and was confined to the reporter cassette. Silencing was associated with high levels of de novo DNA methylation at the targeted locus and was dependent on this epigenetic mark for its propagation. Finally, transient transfection of 3 ATRs targeted to the promoter region of the Beta-2-microglobulin (B2M) gene resulted in the loss of surface expression of B2M and, consequently, of the MHC-I molecules in up to 80% of treated cells. This phenotype was associated with a switch in the epigenetic and transcriptional state of the constitutively active B2M gene, which became highly decorated with DNA methylation and deprived of RNA PolII and of its transcript. Of note, silencing was resistant to IFN-γ treatment, a potent B2M inducer. Overall, these data provide the first demonstration of efficient and stable silencing of an endogenous gene upon transient delivery of ATRs. This result was made possible by repurposing the machinery involved in silencing of ERVs, which instructs self-sustaining repressive epigenetic states on the gene of interest. While silencing of B2M might be used to generate universally transplantable allogeneic cells, our hit-and-run strategy provides a powerful new alternative to conventional gene silencing for the treatment of several diseases. (LN & AL co-authorship

729 inheritable silencing of endogenous gene by hit and run targeted epigenetic editing

Gene silencing holds great promise for the treatment of several diseases and can be exploited to investigate gene function and activity of the regulatory genome. Here, we develop a novel modality of gene silencing that exploits epigenetics to achieve stable and highly efficient repression of target genes. To this end, we generated Artificial Transcriptional Repressors (ATRs), chimeric proteins containing a custom-made DNA binding domain fused to the effector domain of chromatin-modifying enzymes involved in silencing process of Endogenous RetroViruses (ERVs). By performing iterative rounds of selection in cells engineered to report for synergistic activity of candidate effector domains, we identified a combination of 3 domains (namely KRAB, DNMT3A and DNMT3L) that, when transiently co-assembled on the promoter of the reporter cassette, recreate a powerful embryonic-specific repressive complex capable of inducing full and long-term (>150 days) silencing of transgene expression in up to 90% of the cells. The ATR-induced silencing was cell type and locus independent, and resistant to metabolic activation of the cells. Importantly, these findings were holding true also for endogenous genes embedded in their natural chromatin context, as shown for the highly and ubiquitously expressed B2M gene. Here, transient co-delivery of TALE-based ATRs resulted in loss of surface expression of B2M and, consequently, of the MHC-I molecules in up to 80% of the cells. This phenotype was associated with a drastic switch in the epigenetic and transcriptional state of the constitutively active B2M promoter, which become highly decorated with de novo DNA methylation and deprived of RNAP II. Importantly, silencing was sharply confined to the targeted gene and resistant to INF-γ, a potent natural activator of B2M. We further extended these studies by showing that our silencing approach is portable to the CRISPR/dCas9 DNA binding technology. In this setting, comparable levels of B2M silencing (up to 80%) were achieved using either pools or even individual sgRNAs coupled to dCas9-based ATRs. Yet, adoption of this technology allowed performing simultaneous, highly efficient multiplex gene silencing within the same cell, as shown for B2M, IFNAR1 and VEGFA. Finally, we assessed resistance of the silenced gene to activity of potent artificial transcription activators and chromatin remodelers, and found that only targeted DNA demethylation was able to reawaken the silent gene. This allowed performing iterative cycles of silencing and reactivation of the same gene in the same cell population. Overall, these data provide the first demonstration of efficient and stable epigenetic silencing of endogenous genes upon transient delivery of ATRs. This was accomplished by repurposing the ERVs silencing machinery, which instructs self-sustaining repressive epigenetic states to the target gene. While silencing of B2M might be used to generate universally transplantable allogeneic cells, our hit-and-run strategy provides a powerful new alternative to conventional gene silencing for both basic and translational research

Benefits and challenges of Bbg data in healthcare. An overview of the European initiatives

Healthcare systems around the world are facing incredible challenges due to the ageing population and the related disability, and the increasing use of technologies and citizen's expectations. Improving health outcomes while containing costs acts as a stumbling block. In this context, Big Data can help healthcare providers meet these goals in unprecedented ways. The potential of Big Data in healthcare relies on the ability to detect patterns and to turn high volumes of data into actionable knowledge for precision medicine and decision makers. In several contexts, the use of Big Data in healthcare is already offering solutions for the improvement of patient care and the generation of value in healthcare organizations. This approach requires, however, that all the relevant stakeholders collaborate and adapt the design and performance of their systems. They must build the technological infrastructure to house and converge the massive volume of healthcare data, and to invest in the human capital to guide citizens into this new frontier of human health and well-being. The present work reports an overview of best practice initiatives in Europe related to Big Data analytics in public health and oncology sectors, aimed to generate new knowledge, improve clinical care and streamline public health surveillance