High-sensitivity analysis of clonal hematopoiesis reveals increased clonal complexity of potential-driver mutations in severe COVID-19 patients.

Whether Clonal Hematopoiesis (CH) represents a risk factor for severity of the COVID-19 disease remains a controversial issue. We report the first high- sensitivity analysis of CH in COVID-19 patients (threshold of detection at 0.5% vs 1 or 2% in previous studies). We analyzed 24 patients admitted to ICU for COVID-19 (COV-ICU) and 19 controls, including healthy subjects and asymptomatic SARS-CoV2-positive individuals. Despite the significantly higher numbers of CH mutations identified (80% mutations with <2% variant allele frequency, VAF), we did not find significant differences between COV-ICU patients and controls in the prevalence of CH or in the numbers, VAF or functional categories of the mutated genes, suggesting that CH is not overrepresented in patients with COVID-19. However, when considering potential drivers CH mutations (CH-PD), COV-ICU patients showed higher clonal complexity, in terms of both mutation numbers and VAF, and enrichment of variants reported in myeloid neoplasms. However, we did not score an impact of increased CH-PD on patient survival or clinical parameters associated with inflammation. These data suggest that COVID-19 influence the clonal composition of the peripheral blood and call for further investigations addressing the potential long-term clinical impact of CH on people experiencing severe COVID-19. We acknowledge that it will indispensable to perform further studies on larger patient cohorts in order to validate and generalize our conclusions. Moreover, we performed CH analysis at a single time point. It will be necessary to consider longitudinal approaches with long periods of follow-up in order to assess if the COVID-19 disease could have an impact on the evolution of CH and long-term consequences in patients that experienced severe COVID-19.

Lower probability and shorter duration of infections after COVID-19 vaccine correlate with anti-SARS-CoV-2 circulating IgGs.

The correlation between immune responses and protection from SARS-CoV-2 infections and its duration remains unclear. We performed a sanitary surveillance at the European Institute of Oncology (IEO) in Milan over a 17 months period. Pre-vaccination, in 1,493 participants, we scored 266 infections (17.8%) and 8 possible reinfections (3%). Post-vaccination, we identified 30 infections in 2,029 vaccinated individuals (1.5%). We report that the probability of infection post-vaccination is i) significantly lower compared to natural infection, ii) associated with a significantly shorter median duration of infection than that of first infection and reinfection, iii) anticorrelated with circulating antibody levels.

COVID-19 and radiotherapy: impact on work and personal life of Lombardy residents during first lockdown, survey endorsed by AIRO Young.

AIM: Since 20 February 2020, Lombardy has been one of the most affected areas worldwide by the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study is to evaluate work and psychological impact of COVID-19 on Lombardy radiation therapy (RT) residents in the first 3 months of the outbreak (first lockdown). METHODS: An online questionnaire (22 multiple choice questions) via Microsoft Forms was administered on 30 May 2020 to RT residents. RESULTS: Nineteen Lombardy RT residents responded to the survey. Nineteen percent of residents underwent a nasal swab and 11% were quarantined. Seventeen residents (89%) reported an increase in workload. Twelve residents (63%) did not find any difference in terms of work distress; worsening was highlighted in 5 cases (26%). The majority has never considered the possibility of stopping work due to excessive stress (89%). Almost all the residents experienced self- or relative-referred apprehension (95%). Ninety-five percent reported having missed extra-work social relationships. Most of the sample noted worsening sleep quality and difficulty concentrating (69%). No residents requested psychological support, even if provided by the hospital. CONCLUSION: Overall, the residents adapted to the new workplace scenario, although some health risks and well-being challenges have been reported. An extension of the survey to all Italian RT residents endorsed by Italian Association of Radiotherapy and Clinical Oncology "Young AIRO" will allow an evaluation of COVID-19 impact on a national level. A second survey is planned to underline differences between the first lockdown and the current situation of the pandemic.

[How to evaluate the application of Clinical Governance tools in the management of hospitalized hyperglycemic patients: results of a multicentric study]. / Valutazione dell'applicazione degli strumenti di governance clinica nella gestione del paziente iperglicemico ospedalizzato: risultati di un'analisi multicentrica.

Risk management is a key tool in Clinical Governance. Our project aimed to define, share, apply and measure the impact of tools and methodologies for the continuous improvement of quality of care, especially in relation to the multi-disciplinary and integrated management of the hyperglycemic patient in hospital settings. A training project, coordinated by a scientific board of experts in diabetes and health management and an Expert Meeting with representatives of all the participating centers was launched in 2014. The project involved eight hospitals through the organization of meetings with five managers and 25 speakers, including diabetologists, internists, pharmacists and nurses. The analysis showed a wide variability in the adoption of tools and processes towards a comprehensive and coordinated management of hyperglycemic patients.

Literature review of gender differences in respiratory conditions: a focus on asthma and Chronic Obstructive Pulmonary Disease (COPD).

BACKGROUND: Gender differences are evident in many common health conditions, especially respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). The aim of this review was to identify published studies describing gender differences in asthma and COPD, in particular regarding pathophysiology, diagnosis and treatment, with a focus on Italian data. METHODS: a literature review was performed from April to November 2015, using the PubMed scientific database and the following ??eywords: "gender differences" and "asthma" for the asthma review and "gender differences" and "COPD" for the COPD review. RESULTS: Gender differences in asthma are related to age groups. In the female population, asthma is generally more severe and disabling, and presents higher mortality rates with respect to same-age males. COPD prevalence is growing and is underestimated in women, because it tends to be diagnosed with difficulty and at a delayed stage. The same findings were observed when restricting the review to Italian data. CONCLUSION: Clinicians should collaborate to develop a more gender-oriented approach towards diagnosis and treatment of asthma and COPD. In Italy, this would also facilitate measures to improve compliance, particularly among women.

[Survey to assess educational needs of personnel working at Departments of Prevention, Health Districts and Hospital Directions in Italy: questionnaire validation and preliminary results]. / Indagine conoscitiva sulla rilevazione dei bisogni formativi del personale in servizio presso Dipartimenti di prevenzione, Distretti sanitari e Direzioni degli Ospedali: validazione del questionario e risultati preliminari.

AIM: The aim was of this pilot study was to validate a questionnaire to collect information on the number of health professionals, doctors and veterinarians working in the Departments of Prevention, Health Districts and Hospital Directions, their sociodemographic characteristics and cultural-background, define their educational needs, and subsequently extending the study to the maximum number of professionals in the classified services under study. METHODS: The survey was conducted through the use of a questionnaire, designed and prepared by the working group and subsequently reported on-line. Internal consistency of the questionnaire was measured by Cronbach's alpha. RESULTS: Overall, 128 health professionals were enrolled in the study. Their mean age was 57.5 years; 83.6% have a medical degree and 6.3% a degree in veterinary medicine. Most participants (64.8%) are employed by a Health District, 21.1% work in a Department of Prevention and 2.3% are part of a hospital clinical management staff. 32.3% are specialists in only one area, and, in particular, 22% of the sample is a Public Health specialist, 4% respectively are specialists in Occupational Medicine and Forensic Medicine. The alpha values for each section were, for Section A, 0.914; Section B, 0.963; Section C, 0.802; and Section D, 0.945. CONCLUSION: The questionnaire was shown to have good internal reliability. Identifying the educational needs of public health professionals, and the innovative and emerging issues that impact public health is essential to allow for National Health Service staff to be able to respond to the rapid cultural changes that characterize the current global health context.

[Burden of medical errors in Italy: an analysis of the literature]. / Burden epidemiologico ed economico dell'errore medico: analisi della letteratura nel nostro Paese.

INTRODUCTION: Medical malpractice and litigation have a significant impact on the Italian National Health Service. The aim of this study was to analyze the state of the art of medical errors in Italy, in particular, assessing which specialties are most affected. METHODS: We performed a literature search in PubMed, Google Scholar; institutional websites (Ministry of Health, Higher Institute of Health, National Agency for Regional Health Services, National Institute of Statistics, National Research Council, Court of Auditors), gray literature and specialized magazines. RESULTS: Results show that data regarding the frequency of medical errors and the effectiveness of prevention measures in Italy are scarce. Most papers published on this topic refer to a few specialties, including Surgery, Radiology, Cardiology, and Laboratory medicine. Surgery is the specialty most affected. CONCLUSIONS: Despite a growing attention towards patient safety and quality of healthcare, medical errors continue to occur in clinical practice. Most errors are not due to individual incompetence or negligence but they are rooted in system breakdowns. A systematic approach is therefore required, based on: an analysis of critical aspects in the system; the selection and implementation, at different levels of the system, of appropriate and evidence-based risk management interventions involving all stakeholders; a context analysis to identify barriers and facilitators for change; a performance assessment to verify results and identify actions for improvement.

Knowledge, opinions and attitudes of Italian mothers towards HPV vaccination and Pap test.

AIM: This study evaluated the knowledge and attitudes of Italian mothers - whose daughters had been vaccinated in 2012 - towards primary (anti-HPV vaccination) and secondary (Pap test screening) cervical cancer prevention, as well as sources of information and mother-daughter communication on health issues. METHODS: The survey - part of a multicenter study carried out in 4 Italian cities (Ferrara, Rome, Cassino and Palermo) - was conducted through self-administered questionnaires. The first univariate analysis evaluated differences between mothers of under-18s and over-18s relative to knowledge and attitudes on HPV vaccination and Pap test. The second univariate analysis evaluated differences between the 2 groups of mothers and possible geographical variations regarding the sources of information on HPV and Pap test. RESULTS: The sample proved knowledgeable about the correlation between HPV and cervical cancer (>85%) but less aware of other HPV-related diseases. HPV vaccination should be administered before first sexual intercourse according to mothers of over-18s, and to 14- to 17-year-olds according to mothers of under-18s. Up to 88% of mothers of under-18s and 80% of mothers of over-18s declared that the vaccine should be given free of charge. More mothers of under-18s consulted a general practitioner (GP) or gynecologist before deciding to vaccinate their daughters. Mothers of under-18s received information on HPV vaccination mainly from GPs and gynecologists, while mothers of over-18s were informed through TV and books/journals. Over 80% of the sample declared satisfaction with the information received from their gynecologist during the Pap test. CONCLUSIONS: The findings provide useful information for the development of effective public health interventions that may help improve acceptance of HPV vaccination among mothers.

Does clinical governance influence the appropriateness of hospital stay?

BACKGROUND: Clinical Governance provides a framework for assessing and improving clinical quality through a single coherent program. Organizational appropriateness is aimed at achieving the best health outcomes and the most appropriate use of resources. The goal of the present study is to verify the likely relationship between Clinical Governance and appropriateness of hospital stay. METHODS: A cross-sectional study was conducted in 2012 in an Italian Teaching Hospital. The OPTIGOV(©) (Optimizing Health Care Governance) methodology was used to quantify the level of implementation of Clinical Governance globally and in its main dimensions. Organizational appropriateness was measured retrospectively using the Italian version of the Appropriateness Evaluation Protocol to analyze a random sample of medical records for each clinical unit. Pearson-correlation and multiple linear regression were used to test the relationship between the percentage of inappropriate days of hospital stay and the Clinical Governance implementation levels. RESULTS: 47 Units were assessed. The percentage of inappropriate days of hospital stay showed an inverse correlation with almost all the main Clinical Governance dimensions. Adjusted multiple regression analysis resulted in a significant association between the percentage of inappropriate days and the overall Clinical Governance score (ß = -0.28; p < 0.001; R-squared = 0.8). EBM and Clinical Audit represented the Clinical Governance dimensions which had the strongest association with organizational appropriateness. CONCLUSIONS: This study suggests that the evaluation of both Clinical Governance and organizational appropriateness through standardized and repeatable tools, such as OPTIGOV(©) and AEP, is a key strategy for healthcare quality. The relationship between the two underlines the central role of Clinical Governance, and especially of EBM and Clinical Audit, in determining a rational improvement of appropriateness levels.

Health technology assessment of belimumab: a new monoclonal antibody for the treatment of systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is treated with anti-inflammatory and immunosuppressive drugs and off-label biologics. Belimumab is the first biologic approved after 50 years as an add-on therapy for active disease. This paper summarizes a health technology assessment performed in Italy. METHODS: SLE epidemiology and burden were assessed using the best published international and national evidences and efficacy and safety of belimumab were synthesized using clinical data. A cost-effectiveness analysis was performed by a lifetime microsimulation model comparing belimumab to standard of care (SoC). Organizational and ethical implications were discussed. RESULTS: Literature review showed that SLE affects 47 per 100,000 people for a total of 28,500 patients in Italy, 50% of whom are affected by active form of the disease despite SoC. These patients, if autoantibodies and anti-dsDNA positive with low complement, are eligible for belimumab. SLE determines work disability and a 2-5-fold increase in mortality. Belimumab with SoC may prevent 4,742 flares in three years being cost-effective with an incremental cost-effectiveness ratio of €32,859 per quality adjusted life year gained. From the organizational perspective, the development of clear and comprehensive clinical pathways is crucial. CONCLUSIONS: The assessment supports the use of belimumab into the SLE treatment paradigm in Italy.

The prevention of postmenopausal osteoporotic fractures: results of the Health Technology Assessment of a new antiosteoporotic drug.

OBJECTIVE: The Health Technology Assessment (HTA) approach was applied to denosumab in the prevention of osteoporotic fractures in postmenopausal women. METHOD: Epidemiological, clinical, technical, economic, organizational, and ethical aspects were considered. Medical electronic databases were accessed to evaluate osteoporosis epidemiology and therapeutical approaches. A budget impact and a cost-effectiveness analyses were performed to assess economic implications. Clinical benefits and patient needs were considered with respect to organizational and ethical evaluation. RESULTS: In Italy around four millions women are affected by osteoporosis and have a higher risk for fractures with 70,000 women being hospitalized every year. Bisphosphonates and strontium ranelate are recommended as first line treatment for the prevention of osteoporotic fractures. Denosumab is effective in reducing vertebral, nonvertebral, and hip/femoral fractures with an advantage of being administered subcutaneously every six months. The budget impact analysis estimated a reduction in costs for the National Health Service with the introduction of denosumab. Furthermore, the economic analysis demonstrated that denosumab is cost-effective in comparison to oral bisphosphonates and strontium ranelate. Denosumab can be administered in outpatients by involving General Practitioners in the management. Ethical evaluation is positive because of its efficacy and compliance. CONCLUSION: Denosumab could add value in the prevention of osteoporotic fractures.

Building successful collaborations between Public Health and Primary Health Care.

Public Health (PH) and Primary Health Care (PHC) need to be better integrated, at different levels of the healthcare system, in order to improve health and social outcomes. The aim of this study was to review international models and approaches supporting the integration of PH and PHC and to classify these according to their main focus. A literature search was performed using the main scientific databases, to identify national and international journal publications regarding models to support integration between PH and PHC. The final set of the documents provided a broad coverage of the topic. Four models of integration were identified: general integration, chronic disease prevention, targeted prevention or care delivery and infection control. Models differed in their levels of implementation, stages of development and focus. This review, by classifying the main characteristics and results of the experiences retrieved, indicates a relatively scarce use of integration models in the global health care landscape, with the exception of Canada. In fact, Canada has been a leader in developing models of integrated health systems that combine tailored approaches to influence personal health behaviour and community-oriented approaches to influence the health of the population. The review also revealed a general lack of experience in evaluating the sustainability of integration between PH and PHC, not only in terms of cost-effectiveness, but also in terms of better health and work conditions and self-perceived quality of care in the population. Collaboration between PH and PHC seems to be an important strategy for achieving principles of equity and access in health care and for ensuring a more equal distribution of health care services.

Are age and gender associated to tobacco use and knowledge among general practitioners? Results of a survey in Italy.

OBJECTIVES: The aim of this study was to assess knowledge and opinions of Italian general practitioners about the effectiveness of smoking cessation interventions and physicians' attitudes in addressing tobacco-related issues. METHODS: The survey was carried out through a questionnaire administered to general practitioners (GPs) attending a medical refresher course. 133 Italian GPs participated in the study with a mean age of 51.4 years (SD = 6.2). RESULTS: The GPs had good knowledge about the predictors of smoking onset, pharmacotherapies for tobacco cessation and the clinical guidelines recommendations. Wrong answers were encountered for the prevalence of smokers in Italy, the Fagerström Test for nicotine dependence and minimal advice. Females were more subjected to higher knowledge about tobacco, and at lower risk to be a smoker/ex smoker. Furthermore, physicians ≥ 50 years old living in northern Italy had higher knowledge score. CONCLUSIONS: Physician education on tobacco counseling is associated to increased comfort and practice in advising patients who smoke. Tobacco cessation training might increase the success rate of helping patients to quit smoking.

Economic value of influenza vaccination.

Influenza epidemics are responsible for high mortality and morbidity rates in particular among elderly and high risk groups. This review is aimed at assessing the economic value of vaccination in these groups. A search of full economic evaluations of influenza vaccination in comparison with no interventions was performed on PubMed from January 1990 to May 2011. Only economic evaluations dealing with elderly and high risk groups were considered. The quality of selected articles was assessed through Drummond's checklist. Sixteen cost-effectiveness analyses and four cost-benefit analyses were included: overall, the quality of studies was fairly good. The vaccination was demonstrated to be cost-effective or cost-saving in almost all studies, independently by the perspective and the type of analysis. Influenza vaccination is a worthwhile intervention from the pharmacoeconomic view-point, anyway a standardization of methods should be desirable in order to guarantee the comparability and transferability of results.

Peer pressure and public reporting within healthcare setting: improving accountability and health care quality in hospitals.

In the last few years, the need of public reporting of health outcomes has acquired a great importance. The public release of performance results could be a tool for improving health care quality and many attempts have been made in order to introduce public reporting programs within the health care context at different levels. It would be necessary to promote the introduction of a standardized set of outcome and performance measures in order to improve quality of health care services and to make health care providers aware of the importance of transparency and accountability.

Tobacco use prevalence, knowledge and attitudes among Italian hospital healthcare professionals.

BACKGROUND: Healthcare professionals play a key role in tobacco use prevention because they are considered as model by patients. This multicenter study was aimed to evaluate smoking prevalence, knowledge and attitudes towards tobacco among Italian hospital professionals. METHODS: A cross-sectional study was carried out using a questionnaire administered to healthcare professionals in seven Italian hospitals, to investigate personal and occupational data, knowledge, attitudes, job setting, clinical activities, smoking habits and pattern for current smokers. Potential predictors of current smoking habits were evaluated using multiple logistic regressions. RESULTS: Sample population was comprised of 1082 health professionals (51.4% females; mean age was 37.3 years: 25.3% were nurses, 24.5% medical doctors, 17.1% students and 33.1% other healthcare workers). Smoking prevalence was 44%. Among responders, 67.7% considered healthcare professional as a model for citizens, 90.5% declared to see colleagues smoking cigarettes inside the hospital (47.4% in the dependents' toilets, 33.4% in the department kitchens and 4.7% in the patient room). Multivariate analysis showed that healthcare professionals working in Naples had a higher risk to be smokers in comparison to Rome [odds ratio (OR) = 2.29; 95% confidence interval (CI) 1.40-3.73]. Compared to medical doctors, post-graduate students (OR = 3.42; 95% CI: 1.81-6.44), nurses (OR = 2.48; 95% CI 1.51-4.08), nursing students (OR = 1.91; 95% CI 1.08-3.38) and auxiliary personnel (OR = 2.72; 95% CI 1.51-4.88), showed a higher likelihood of smoking. CONCLUSIONS: Among Italian hospital personnel there is a paradoxically large prevalence of smokers, higher than in the general population. Interventions aimed for the development of an adequate culture of health promotion, among these professionals, are urgently needed.

[Pay for performance in primary care]. / Pay for Performance nell'assistenza primaria: per una sanità di qualità

Pay for Performance is a tool that links payment of healthcare professionals to the quality of health outcomes and processes. In this article the authors discuss the results of a literature review on the subject, highlighting the importance of introducing a Pay for Performance system in primary care, and the advantages and critical issues associated with the system. The experience of the British National Health Service and possible uses of the described payment system in Italy are also briefly discussed.

OPTIGOV - A new methodology for evaluating Clinical Governance implementation by health providers.

BACKGROUND: The aim of Clinical Governance (CG) is to the pursuit of quality in health care through the integration of all the activities impacting on the patient into a single strategy.OPTIGOV (Optimizing Health Care Governance) is a methodology for the assessment of the level of implementation of CG within healthcare organizations. The aim of this paper is to explain the process underlying the development of OPTIGOV, and describe its characteristics and steps. METHODS: OPTIGOV was developed in 2006 by the Institute of Hygiene of the Catholic University of the Sacred Heart and Eurogroup Consulting Alliance. The main steps of the process were: choice of areas for analysis and questionnaire development, based on a review of scientific literature; assignment of scores and weights to individual questions and areas; implementation of a software interfaceable with Microsoft Office. RESULTS: OPTIGOV consists of: a) a hospital audit with a structured approach; b) development of an improvement operational plan. A questionnaire divided into 13 areas of analysis is used. For each area there is a form with a variable number of questions and "closed" answers. A score is assigned to each answer, area of analysis, healthcare department and unit. The single scores can be gathered for the organization as a whole.The software application allows for collation of data, calculation of scores and development of benchmarks to allow comparisons between healthcare organizations. Implementation consists of three stages: the preparation phase includes a kick off meeting, selection of interviewees and development of a survey plan. The registration phase includes hospital audits, reviewing of hospital documentation, data collection and score processing. Lastly, results are processed, inserted into a final report, and discussed in a meeting with the Hospital Board and in a final workshop. CONCLUSIONS: The OPTIGOV methodology for the evaluation of CG implementation was developed with an evidence-based approach. The ongoing adoption of OPTIGOV in several projects will put to the test its potential to realistically represent the organization status, pinpoint criticalities and transferable best practices, provide a plan for improvement, and contribute to triggering changes and pursuit of quality in health care.

Does quality of observational studies affect the results of a meta-analysis?: the case of cigarette smoking and pancreatic cancer.

OBJECTIVES: A meta-analysis of observational studies on association between cigarette smoking and pancreatic cancer was performed to focus, particularly, on the role of the studies' quality in affecting meta-analysis results. METHODS: A bibliographic search was carried out on PubMed and EMBASE databases until February 15, 2008. Key words were "pancreatic neoplasms," "pancreatic cancer," "smoking," "smoke," "cigarette," "case-control studies," and "cohort studies." Studies about cigarette smoking and pancreatic cancer were selected and assessed on quality. STATA 9.0 was used. RESULTS: Six cohort studies and 24 case-control studies were selected, with median quality scores of 8 (range, 3) and 10 (range, 8), respectively. Pooled case-control studies' odds ratio (OR) and cohort studies' risk ratio were, respectively, 1.45 (95% confidence interval [CI], 1.33-1.57) and 1.78 (95% CI, 1.64-1.92). After stratifying for quality scoring, high-quality-scored case-control studies yielded an OR of 1.38 (95% CI, 1.27-1.49), whereas the others gave an OR of 1.52 (95% CI, 1.34-1.73). The results of meta-analysis for cohort studies showed a risk ratio of 1.74 (95% CI, 1.61-1.90) and of 2.10 (95% CI, 1.64-2.67), respectively, for high- and low-quality score studies. CONCLUSIONS: There is evidence that cigarette smoking is an important risk factor for pancreatic cancer, but the estimate of the association greatly relies on the studies' quality.