Ukrainian refugee crisis management in the Local Health Authority Roma 1: the challenges of implementing public health policies and lessons learned.

BACKGROUND: The conflict between Russia and Ukraine has strained the health systems of countries that welcome war refugees on all levels, from national to local. Despite the Public Health guidelines regarding assistance being published on the topic, the scientific literature currently lacks evidence on the experience of applying theory in practice. This study aims to describe evidence-based practices that were implemented and to provide a detailed description of emerging problems and solutions pertaining Ukrainian refugee assistance in the context of one of the biggest Local Health Authorities in Italy (LHA Roma 1). METHODS: LHA Roma 1 developed a strategic plan based on local expertise, national and international guidelines to ensure infectious disease prevention and control, as well as continuity of care for non-communicable diseases and mental health. RESULTS: The insertion of Ukrainian refugees in the National Health System through an identification code assignment and other services such as COVID-19 swab and vaccination were provided either in one of the three major assistance hubs or in local district level ambulatories spread throughout the LHA. Many challenges were faced during the implementation phase of the outlined practice guidelines, which required sensible and timely solutions. These challenges include the necessity of rapid resource provision, overcoming linguistic and cultural barriers, guaranteeing a standard of care across multiple sites and coordination of interventions. Public Private Partnerships, the creation of a centralized multicultural and multidisciplinary team and the mutually beneficial collaboration with the local Ukrainian community were essential to guarantee the success of all operations. CONCLUSIONS: The experience of LHA Roma 1 helps shed light on the importance of leadership in emergency settings and how a dynamic relationship between policy and practice would allow each intervention to be modulated according to the local environment, to better realize the potential of local realities to provide appropriate health interventions to all those in need.

Health technology assessment of whole genome sequencing in the diagnosis of genetic disorders: a scoping review of the literature.

OBJECTIVE: The aim of this scoping review is to map the available evidence about the use of health technology assessment (HTA) in the assessment of whole genome sequencing (WGS). METHODS: A scoping review methodology was adopted. The population, concept, and context framework was used to build up the research question and to establish the eligibility criteria. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews was adopted to implement a comprehensive search strategy. Evidence was retrieved from scientific databases and HTA organizations Web sites. Reports were classified as full HTA, mini-HTA, rapid reviews or other. RESULTS: The search strategy identified seven reports. Five HTA organizations from five countries elaborated the reports: one full HTA, four rapid reviews, and two classified as others. The reports were mainly focused on the evaluation of the clinical utility and cost-effectiveness of genome-wide sequencing as well as informing policy questions by providing analyses of organizational and ethical considerations. CONCLUSIONS: Few HTA organizations are drafting reports for WGS. It is essential to stimulate a critical reflection during the elaboration of HTA reports for WGS to steer choices of decision makers in the establishment of priorities for research and policy and reimbursement rates.

Whole genome sequencing diagnostic yield for paediatric patients with suspected genetic disorders: systematic review, meta-analysis, and GRADE assessment.

BACKGROUND: About 80% of the roughly 7,000 known rare diseases are single gene disorders, about 85% of which are ultra-rare, affecting less than one in one million individuals. NGS technologies, in particular whole genome sequencing (WGS) in paediatric patients suffering from severe disorders of likely genetic origin improve the diagnostic yield allowing targeted, effective care and management. The aim of this study is to perform a systematic review and meta-analysis to assess the effectiveness of WGS, with respect to whole exome sequencing (WES) and/or usual care, for the diagnosis of suspected genetic disorders among the paediatric population. METHODS: A systematic review of the literature was conducted querying relevant electronic databases, including MEDLINE, EMBASE, ISI Web of Science, and Scopus from January 2010 to June 2022. A random-effect meta-analysis was run to inspect the diagnostic yield of different techniques. A network meta-analysis was also performed to directly assess the comparison between WGS and WES. RESULTS: Of the 4,927 initially retrieved articles, thirty-nine met the inclusion criteria. Overall results highlighted a significantly higher pooled diagnostic yield for WGS, 38.6% (95% CI: [32.6 - 45.0]), in respect to WES, 37.8% (95% CI: [32.9 - 42.9]) and usual care, 7.8% (95% CI: [4.4 - 13.2]). The meta-regression output suggested a higher diagnostic yield of the WGS compared to WES after controlling for the type of disease (monogenic vs non-monogenic), with a tendency to better diagnostic performances for Mendelian diseases. The network meta-analysis showed a higher diagnostic yield for WGS compared to WES (OR = 1.54, 95%CI: [1.11 - 2.12]). CONCLUSIONS: Although whole genome sequencing for the paediatric population with suspected genetic disorders provided an accurate and early genetic diagnosis in a high proportion of cases, further research is needed for evaluating costs, effectiveness, and cost-effectiveness of WGS and achieving an informed decision-making process. TRIAL REGISTRATION: This systematic review has not been registered.

Incremental net benefit of whole genome sequencing for newborns and children with suspected genetic disorders: Systematic review and meta-analysis of cost-effectiveness evidence.

BACKGROUND: The introduction of massive parallel sequencing has contributed to a decline in sequencing costs. In recent years, whole-exome sequencing (WES) and whole-genome sequencing (WGS) have been increasingly adopted for diagnostic purposes in individuals with suspected genetic diseases. However, a debate is still ongoing in the scientific community about the superiority of WGS over WES in terms of cost-effectiveness. The aim of this study is to assess whether WGS, for the pediatric population with suspected genetic disorders, is cost-effective with respect to WES and chromosomal microarray (CMA) by pooling incremental net benefits. MATERIALS AND METHODS: Articles were retrieved from PubMed, Web of Science, Embase and Scopus from 2015 to 2021. The dominance ranking matrix (DRM) tool was adopted to provide a qualitative synthesis of all the included studies. Incremental net benefits (INBs) were estimated and meta-analysis was implemented to pool INBs across studies. RESULTS: The database search identified 1600 publications of which four articles were considered eligible for the meta-analysis. The pooled INB of WGS over WES was estimated at I$4073 (95% CI I$2426 - I$5720). The pooled INB of WGS over CMA amounted to I$6003 (95% CI I$2863 - I$9143). CONCLUSIONS: WGS could be cost-effective in the diagnostic workup of affected infants and children. Further economic evaluations however are needed for comparing WGS versus WES and confirm the present conclusions.

Assessing the potentiality of algorithms and artificial intelligence adoption to disrupt patient primary care with a safer and faster medication management: a systematic review protocol.

INTRODUCTION: In primary care, almost 75% of outpatient visits by family doctors and general practitioners involve continuation or initiation of drug therapy. Due to the enormous amount of drugs used by outpatients in unmonitored situations, the potential risk of adverse events due to an error in the use or prescription of drugs is much higher than in a hospital setting. Artificial intelligence (AI) application can help healthcare professionals to take charge of patient safety by improving error detection, patient stratification and drug management. The aim is to investigate the impact of AI algorithms on drug management in primary care settings and to compare AI or algorithms with standard clinical practice to define the medication fields where a technological support could lead to better results. METHODS AND ANALYSIS: A systematic review and meta-analysis of literature will be conducted querying PubMed, Cochrane and ISI Web of Science from the inception to December 2021. The primary outcome will be the reduction of medication errors obtained by AI application. The search strategy and the study selection will be conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the population, intervention, comparator and outcome framework. Quality of included studies will be appraised adopting the quality assessment tool for observational cohort and cross-sectional studies for non-randomised controlled trials as well as the quality assessment of controlled intervention studies of National Institute of Health for randomised controlled trials. ETHICS AND DISSEMINATION: Formal ethical approval is not required since no human beings are involved. The results will be disseminated widely through peer-reviewed publications.

Cervical cancer elimination in Italy: Current scenario and future endeavors for a value based prevention.

Background: Cervical Cancer (CC) is a vaccine-preventable disease, and it is treatable if diagnosed early and managed properly. However, it is the fourth most common cancer in women worldwide with about 604,127 cases and 341,831 deaths in 2020. In Italy, it represents the fifth most common cancer in women under 50 years of age with about 2,400 new cases in 2020. The CC elimination is today a global public health goal published by the World Health Organization (WHO) in 2020 and a commitment of the European Union that has included it in Europe's Beating Cancer Plan. Therefore, urgent action is needed, at international and national level, to implement value-based interventions regarding vaccination, screening and timely management of the disease. Our study aims to describe the state of the art of Human Papilloma Virus (HPV) prevention in Italy and to get a consensus on indicators for monitoring the progress toward CC elimination at national level. Methods: The study envisaged the following activities: research and synthesis of the evidence on strategies and actions for CC elimination at regional Italian level; identification of indicators to monitor such strategies/actions; organization of a multi-stakeholder consensus to reach the agreement on main indicators to be used in Italy. Results: As for HPV vaccination coverage, the last Italian available data (December 31st, 2020) showed that it was way below the target (95%) with full cycle vaccination coverage ranging from 6 to 61.7% in female adolescents and from 5.4 to 55.4% in male adolescents (2008 birth cohorts). The coverage rate of CC screening is variable with a range of 61.7-89.6%. Furthermore, coverage rates due to organized screening programs (excluding out-of-pocket screening) shows a range from 20.7 to 71.8%. The mapping of the Italian Regions highlighted an important regional heterogeneity in respect to organizational/operational issue of HPV vaccination and CC screening. Indicators for monitoring CC elimination strategies have been drawn from the Australian experience and distinguished by disease outcomes, vaccination coverage, screening participation and treatment uptake. The highest consensus was reached for the following indicators: CC incidence; detection of high-grade cervical disease; CC mortality; full cycle vaccination coverage; screening participation; high-grade cervical disease treatment rates; CC treatment rates. Conclusions: The assessment of the current status of CC elimination as overarching goal beyond the achievement of vaccine, screening and treatment targets represents the first step for the identification of interventions to be implemented to accelerate the path toward CC elimination. Based on this and following the WHO call, a value-based approach is proposed to untangle the full benefit of HPV-related cancers elimination strategies and identify priority and best practices.

Dealing with COVID-19 Epidemic in Italy: Responses from Regional Organizational Models during the First Phase of the Epidemic.

As the COVID-19 outbreak traveled through various Italian regions, all national and local administrations issued measures to counter the spread of the contagion and organize healthcare. The Italian healthcare system is, indeed, a decentralized system with 21 regional health systems (RHSs), with different models of healthcare service delivery and organization. This study investigates whether a different organization of RHSs would have led to different management of the COVID-19 epidemic, and evaluates the effect of different approaches in epidemic management on the COVID-19 epidemiological trend. A set of indicators is identified by conducting an online synchronous Focus Group, involving an experts panel. A Pearson's correlation test was performed on the values assumed by the historical series of indicators investigate correlations among the trends represented by the indicators or between them and external factors. The comparison between the experiences of the different Italian regions, regarding the management of the epidemic, has helped to confirm and emphasize the importance of a community-based approach in health care-integrated with the hospital's functions for the care of complex conditions and the need for specialized assistance.

Digital laser doppler flowmetry may discriminate "limited" from "diffuse" systemic sclerosis.

OBJECTIVES: To investigate skin blood flux and microvascular functional changes by laser Doppler flowmetry (LD) in patients with systemic sclerosis (SSc) at baseline and following dynamic stimulations. METHODS: Skin blood flux of the dorsal hands was recorded by LD at baseline and after the cold test and the post-occlusive hyperemia test in 59 SSc patients (49 limited cutaneous, 10 diffuse cutaneous). Twenty-five patients with primary Raynaud's phenomenon (PRP), and 31 healthy donors (HD) were studied as controls. RESULTS: After the cold test, SSc patients had a significantly higher reduction of the blood flux (-38.4%+/-28) than PRP (-21.1%+/-37) and HD (-22.1%+/-23) subjects (p<0.05). Within the SSc group, the cold test flux was significantly reduced in limited-SSc (-399%+/-28, p<0.05), but not in diffuse-SSc (-31.2%+/-29), whereas, the time needed to recover the basal flux after the occlusive/ischemic test was significantly longer in diffuse-SSc (18.8s+/-21)than in limited-SSc (4.5s+/-4, p<0.01) or HD (2.2s+/-2, p<0.01) or PRP (0.4s+/-0.7, p<0.01). CONCLUSIONS: These data clearly indicate an impairment of vascular tone regulatory mechanisms in SSc and suggest that a peculiar pathogenic mechanism may be involved in different SSc subset. Nevertheless, it has clear that PRP and SSc-associated RP have a distinct pattern at LD evaluation, and monitoring patients with PRP could be helpful to understand whether a change in the LD pattern might predict the development of SSc.