LA VALUTAZIONE E L’IMPLEMENTAZIONE DEL GOVERNO CLINICO NELLE STRUTTURE OSPEDALIERE E NEI DISTRETTI DELL’ASSISTENZA SANITARIA TERRITORIALE: NUOVI STRUMENTI E METODOLOGIE APPLICATE

Il presente progetto di ricerca descrive sostanzialmente le metodologie sviluppata per analizzare e migliorare il governo dell’erogazione delle prestazioni sanitarie e dell’azione clinica sul paziente (Clinical Governance). In particolare si sintetizza il contributo apportato durante l’intero periodo di dottorato al più complesso progetto di ricerca e realizzazione delle 2 metodologie finalizzate alla valutazione e al miglioramento del livello di governo clinico nelle aziende sanitarie descritte nel corso della presente tesi di Dottorato. Tale contributo è maturato in seno ai dipartimenti di Ingegneria Elettronica, Biomedica e delle Telecomunicazioni (nell’ambito del gruppo di lavoro e di ricerca del Prof. Marcello Bracale) e di Scienze Mediche Preventive (nell’ambito del gruppo di lavoro e di ricerca della Prof.ssa Maria Triassi). Il rapporto professionale con la società Eurogroup Consulting Italia, membro della Eurogroup Consulting Alliance poi diventata, per cessione di ramo d’azienda, CRS (Conoscenza, Ricerca e Sviluppo) Roma per quanto concerne le sue attività relative al’HealthCare & Public Sector, ha invece contribuito alla partnership progettuale della Tesi con l’istituto di Igiene dell’Università Cattolica del Sacro Cuore (dir. Prof. Walter Ricciardi) e hanno favorito il contributo del dottorando alla ricerca e sperimentazione sui temi della valutazione e implementazione del livello di Governo Clinico oggetto della presente tesi di dottorato. Le attività di studio, ricerca e sperimentazione di seguito descritte hanno contribuito nel corso dei 3 anni + 1 di dottorato alla razionalizzazione dei relativi risultati in tecniche di valutazione che sono poi state formalizzate dalla Eurogroup Consulting – CRS Roma e dal Prof. Walter Ricciardi in 2 Metodologie “Optigov” e “Districare” coperte da copyright e applicate/in corso di applicazione in diverse aziende sanitarie sul territorio nazionale. Il periodo di start up della ricerca, della relativa sperimentazione e applicazione sulle aziende sanitarie campione, si è incastrato esattamente con quello di durata complessiva del corso di Dottorato (3 anni +1). La necessità e l’incentivo all’effettuazione delle attività di ricerca e sviluppo finalizzata alla realizzazione di Metodologie per la valutazione del governo clinico, deriva da una serie di esperienze professionali e di studio svolte presso aziende sanitarie italiane ed internazionali. Nel corso di tali esperienze, finalizzate ad interventi di miglioramento dei processi clinici ed amministrativi delle aziende, si è rilevata una crescente sensibilità ai fattori che possono contribuire al verificarsi di eventi dannosi che pregiudichino l’operatività futura dei servizi ospedalieri e/o dei singoli professionisti. Attualmente, in particolare in Italia, il rischio clinico è gestito con un approccio “reattivo”, cioè misurando, a consuntivo, le condizioni di funzionamento dei servizi e dei processi assistenziali e delegando unicamente ad un operatore terzo (solitamente una Compagnia di assicurazioni) la presa in carico del rischio, l’occorrenza degli eventi dannosi e delle sue conseguenze. Anche i processi in genere di miglioramento continuo della qualità assistenziale difettano principalmente di una strutturazione in sistemi ovvero della sistematicità delle azioni correttive anche attraverso sistemi complessi di monitoraggio. Per contro, le fonti scientifiche più accreditate, nonché le esperienze condotte nei contesti più avanzati, individuano, viceversa, nell’implementazione di strumenti e processi per il governo dell’azione clinica sul paziente (Clinical Governance) l’approccio più efficace attualmente a disposizione per la gestione “attiva” del rischio clinico e della qualità assistenziale. La crescente preoccupazione e sensibilizzazione dell'opinione pubblica sulla sicurezza del paziente e sulla qualità nella sanità è stato poi il driver chiave dello sviluppo di Clinical Governance in generale [1-3] e in particolare della ricerca descritta nella presente tesi. Da qui l’interesse per un sostanziale contributo di definizione di 2 metodologie per valutare il livello di implementazione della Clinical Governance nell’ambito delle aziende sanitarie e, quindi, la potenzialità delle stesse ad avviare una gestione “attiva” del miglioramento continuo della qualità assistenziale e del rischio clinico come diretta/indiretta conseguenza . Le metodologie, in estrema sintesi, e nel loro concetto di base, individuano i diversi strumenti della Clinical Governance, li sottopongono ad un processo valutativo nell’ambito di un’azienda sanitaria, e ne identificano il grado di adeguatezza per la gestione del rischio clinico

Characteristics of people living in Italy after a cancer diagnosis in 2010 and projections to 2020

BACKGROUND: Estimates of cancer prevalence are widely based on limited duration, often including patients living after a cancer diagnosis made in the previous 5 years and less frequently on complete prevalence (i.e., including all patients regardless of the time elapsed since diagnosis). This study aims to provide estimates of complete cancer prevalence in Italy by sex, age, and time since diagnosis for all cancers combined, and for selected cancer types. Projections were made up to 2020, overall and by time since diagnosis. METHODS: Data were from 27 Italian population-based cancer registries, covering 32% of the Italian population, able to provide at least 7 years of registration as of December 2009 and follow-up of vital status as of December 2013. The data were used to compute the limited-duration prevalence, in order to estimate the complete prevalence by means of the COMPREV software. RESULTS: In 2010, 2,637,975 persons were estimated to live in Italy after a cancer diagnosis, 1.2 million men and 1.4 million women, or 4.6% of the Italian population. A quarter of male prevalent cases had prostate cancer (n\u2009=\u2009305,044), while 42% of prevalent women had breast cancer (n\u2009=\u2009604,841). More than 1.5 million people (2.7% of Italians) were alive since 5 or more years after diagnosis and 20% since 6515 years. It is projected that, in 2020 in Italy, there will be 3.6 million prevalent cancer cases (+\u200937% vs 2010). The largest 10-year increases are foreseen for prostate (+\u200985%) and for thyroid cancers (+\u200979%), and for long-term survivors diagnosed since 20 or more years (+\u200945%). Among the population aged 6575 years, 22% will have had a previous cancer diagnosis. CONCLUSIONS: The number of persons living after a cancer diagnosis is estimated to rise of approximately 3% per year in Italy. The availability of detailed estimates and projections of the complete prevalence are intended to help the implementation of guidelines aimed to enhance the long-term follow-up of cancer survivors and to contribute their rehabilitation need

Genomic Studies in a Large Cohort of Hearing Impaired Italian Patients Revealed Several New Alleles, a Rare Case of Uniparental Disomy (UPD) and the Importance to Search for Copy Number Variations

Hereditary hearing loss (HHL) is a common disorder characterized by a huge genetic heterogeneity. The definition of a correct molecular diagnosis is essential for proper genetic counseling, recurrence risk estimation, and therapeutic options. From 20 to 40% of patients carry mutations in GJB2 gene, thus, in more than half of cases it is necessary to look for causative variants in the other genes so far identified (~100). In this light, the use of next-generation sequencing technologies has proved to be the best solution for mutational screening, even though it is not always conclusive. Here we describe a combined approach, based on targeted re-sequencing (TRS) of 96 HHL genes followed by high-density SNP arrays, aimed at the identification of the molecular causes of non-syndromic HHL (NSHL). This strategy has been applied to study 103 Italian unrelated cases, negative for mutations in GJB2, and led to the characterization of 31% of them (i.e., 37% of familial and 26.3% of sporadic cases). In particular, TRS revealed TECTA and ACTG1 genes as major players in the Italian population. Furthermore, two de novo missense variants in ACTG1 have been identified and investigated through protein modeling and molecular dynamics simulations, confirming their likely pathogenic effect. Among the selected patients analyzed by SNP arrays (negative to TRS, or with a single variant in a recessive gene) a molecular diagnosis was reached in ~36% of cases, highlighting the importance to look for large insertions/deletions. Moreover, copy number variants analysis led to the identification of the first case of uniparental disomy involving LOXHD1 gene. Overall, taking into account the contribution of GJB2, plus the results from TRS and SNP arrays, it was possible to reach a molecular diagnosis in ~51% of NSHL cases. These data proved the usefulness of a combined approach for the analysis of NSHL and for the definition of the epidemiological picture of HHL in the Italian population

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p < 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p < 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p < 0.0001) or urgent (20.4% vs. 38.5%; p < 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p < 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Standardized Uptake Value Ratio-Independent Evaluation of Brain Amyloidosis

The assessment of in vivo18F images targeting amyloid deposition is currently carried on by visual rating with an optional quantification based on standardized uptake value ratio (SUVr) measurements. We target the difficulties of image reading and possible shortcomings of the SUVr methods by validating a new semi-quantitative approach named ELBA. ELBA involves a minimal image preprocessing and does not rely on small, specific regions of interest (ROIs). It evaluates the whole brain and delivers a geometrical/intensity score to be used for ranking and dichotomic assessment. The method was applied to adniimages 18F-florbetapir images from the ADNI database. Five expert readers provided visual assessment in blind and open sessions. The longitudinal trend and the comparison to SUVr measurements were also evaluated. ELBA performed with area under the roc curve (AUC) = 0.997 versus the visual assessment. The score was significantly correlated to the SUVr values (r = 0.86, p < 10-4). The longitudinal analysis estimated a test/retest error of ≃2.3%. Cohort and longitudinal analysis suggests that the ELBA method accurately ranks the brain amyloid burden. The expert readers confirmed its relevance in aiding the visual assessment in a significant number (85) of difficult cases. Despite the good performance, poor and uneven image quality constitutes the major limitation

Probing the Role of a Regional Quantitative Assessment of Amyloid PET

BACKGROUND: In clinical practice, the amy-PET is globally inspected to provide a binary outcome, but the role of a regional assessment has not been fully investigated yet.OBJECTIVE: To deepen the role of regional amyloid burden and its implication on clinical-neuropsychological features.MATERIALS: Amy-PET and a complete neuropsychological assessment (Trail Making Test, Rey Auditory Verbal Learning Test, semantic verbal fluency, Symbol Digit, Stroop, visuoconstruction) were available in 109 patients with clinical suspicion of Alzheimer's disease. By averaging the standardized uptake value ratio and ELBA, a regional quantification was calculated for each scan. Patients were grouped according to their overall amyloid load: correlation maps, based on regional quantification, were calculated and compared. A regression analysis between neuropsychological assessment and the regional amyloid-beta (Abeta) load was carried out.RESULTS: Significant differences were observed between the correlation maps of patients at increasing levels of Abeta and the overall dataset. The Abeta uptake of the subcortical gray matter resulted not related to other brain regions independently of the global Abeta level. A significant association of semantic verbal fluency was observed with ratios of cortical and subcortical distribution of Abeta which represent a coarse measure of differences in regional distribution of Abeta.CONCLUSION: Our observations confirmed the different susceptibility to Abeta accumulation among brain regions. The association between cognition and Abeta distribution deserves further investigations: it is possibly due to a direct local effect or it represents a proxy marker of a more aggressive disease subtype. Regional Abeta assessment represents an available resource on amy-PET scan with possibly clinical and prognostic implications

Alzheimer\u2019s disease markers from structural MRI and FDG-PET brain images

Despite the widespread use of neuroimaging tools (morphological and functional) in the routine diagnostic of cerebral diseases, the information available by the end user \u2014the clinician\u2014 remains largely limited to qualitative visual analysis. This restriction greatly reduces the diagnostic impact of neuroimaging in routine clinical practice and increases the risk of misdiagnosis. In this context, researches are focussing on the development of sophisticated automatic analyses able to extract clinically relevant information from the captured data. The identification of biological markers at early stages of Alzheimer\u2019s disease (AD) contributes to diagnostic accuracy and adds prognostic value. However, in spite of recent developments, results of structural and functional imaging studies on predicting conversion to AD are not uniform. We provide here an overview of analysis methods and approaches, discussing their contribution to clinical assessment

Deciphering the pathogenesis of the COL4‐related hematuric nephritis: A genotype/phenotype study

Abstract Background Alport syndrome (ATS) is a hereditary progressive hematuric nephropathy associated with sensorineural deafness and ocular abnormalities, which is caused by mutations in the COL4A5 gene (X‐linked ATS) and in two autosomal genes, COL4A4 and COL4A3, responsible of both recessive ATS and, when present in heterozygosity, of a spectrum of phenotypes ranging from isolated hematuria to frank renal disease. Methods Retrospective analysis of the clinical and genetic features of 76 patients from 34 unrelated ATS families (11 with mutations in COL4A5, 11 in COL4A3, and 12 in COL4A4) and genotype/phenotype correlation for the COL4A3/COL4A4 heterozygotes (34 patients from 14 families). Results Eight (24%) of the 34 heterozygous COL4A3 and COL4A4 carriers developed renal failure at a mean age of 57 years, with a significantly lower risk than hemizygous COL4A5 or double heterozygous COL4A3/COL4A4 carriers (p < 0.01), but not different from that of the heterozygous COL4A5 females (p = 0.6). Heterozygous carriers of frameshift/splicing variants in COL4A3/COL4A4 presented a higher risk of developing renal failure than those with missense variants in the glycine domains (p = 0.015). Conclusion The renal functional prognosis of patients with COL4A3/COL4A4‐positive ATS recapitulates that of the X‐linked ATS forms, with differences between heterozygous vs. double heterozygous patients and between carriers of loss‐of‐function vs. missense variants