Systematic analysis of direct antiglobulin test results in post-artesunate delayed haemolysis.

BACKGROUND: Post-artesunate delayed haemolysis (PADH) is common after severe malaria episodes. PADH is related to the "pitting" phenomenon and the synchronous delayed clearance of once-infected erythrocytes, initially spared during treatment. However, direct antiglobulin test (DAT) positivity has been reported in several PADH cases, suggesting a contribution of immune-mediated erythrocyte clearance. The aim of the present study was to compare clinical features of cases presenting a positive or negative DAT. METHODS: Articles reporting clinical data of patients diagnosed with PADH, for whom DAT had been performed, were collected from PubMed database. Data retrieved from single patients were extracted and univariate analysis was performed in order to identify features potentially related to DAT results and steroids use. RESULTS: Twenty-two studies reporting 39 PADH cases were included: median baseline parasitaemia was 20.8% (IQR: 11.2-30) and DAT was positive in 17 cases (45.5%). Compared to DAT-negative individuals, DAT-positive patients were older (49.5 vs 31; p = 0.01), had a higher baseline parasitaemia (27% vs 17%; p = 0.03) and were more commonly treated with systemic steroids (11 vs 3 patients, p = 0.002). Depth and kinetics of delayed anaemia were not associated with DAT positivity. CONCLUSIONS: In this case series, almost half of the patients affected by PADH had a positive DAT. An obvious difference between the clinical courses of patients presenting with a positive or negative DAT was lacking. This observation suggests that DAT result may not be indicative of a pathogenic role of anti-erythrocytes antibodies in patients affected by PADH, but it may be rather a marker of immune activation.

Prevalence of work related musculoskeletal disorders in Italian workers: is there an underestimation of the related occupational risk factors?

BACKGROUND: Work-related musculoskeletal disorders (WMSDs) represent an important socio-economic burden. The current risk assessment and management involved in the ethiopathogenesis of WMSDs is based on observational tools and checklists, which have some limitations in terms of accuracy and reliability. The aim of this study was to assess WMSD prevalence and identify possible correlations with several socio-demographic and work-related variables in a large cohort representative of Italian workers in order to improve our understanding of the WMSD phenomenon. METHODS: This study includes data from INSuLa, a cross-sectional nationally representative survey of health and safety at work, developed by the Italian Workers' Compensation Authority. A total of 8000 Italian workers were included. Multivariate logistic regression analyses were performed to evaluate the association of independent variables, such as workers' perceptions of exposure to biomechanical/ergonomic and video display unit (VDU) risks (Risk Perceived) and the actual risk exposure (Risk Detected) on Back, Lower and Upper limb pain. Socio-demographic, occupational and other health-related variables were included to investigate possible association with musculoskeletal disorders. RESULTS: Workers perceiving a significant exposure to biomechanical/ergonomic and VDU risks but not included in a health surveillance program for them (Risk Perceived/No Risk Detected) have had significantly higher odds of reporting musculoskeletal disorders. Regarding the biomechanical/ergonomic risk these workers are in the 19-24 age range (39.9%), transportation, warehousing/information and communication sectors (38.9%) and are employed in companies with more than 250 workers (35.8%). Regarding VDU risk, workers are in the 45-54 age range (24.5%), professional, financial and business services (38.0%) and come from companies with more than 250 employees (25.6%). CONCLUSIONS: Within the occupational safety and health management systems an appropriate assessment of occupational risk factors correlated to musculoskeletal disorders (mainly biomechanical/ergonomic and VDU) and the correct definition of their exposure levels is essential to adequately prevent the onset of WMSDs. In this regard, our findings provide useful information to design novel approaches, aimed at improving our understanding of emerging risks, identifying gaps in current risk assessment strategies and enhancing workplace interventions are mandatory to improve the occupational risk assessment and management process and therefore implement the subsequent health surveillance systems.

[The elimination of measles and rubella in Italy]. / L'eliminazione del morbillo e della rosolia in Italia.

Despite the WHO target for measles and rubella elimination in 2015, outbreaks still occur in all WHO Regions. After a description of the epidemiological situation of measles and rubella worldwide and especially in Europe, this paper aims to provide a detailed analysis of the current epidemiological context of Italy. The surge in the number of measles cases since the beginning of 2017, together with vaccination coverage still far from the 95% target, requires priority actions to be taken to achieve the elimination goals. Alongside the recently approved decree reintroducing compulsory vaccinations for school admissions, further measures are needed and should include the increase in the commitment of the 21 Regions; the implementation of supplemental immunization activities; improving the communication skills of health care workers; ensuring an effective communication with citizens; the enhancement of the surveillance network.

QT dispersion in mild cognitive impairment: a possible tool for predicting the risk of progression to dementia?

OBJECTIVE: The aim of this research was to investigate relationships between cognitive function and non-invasive, repeatable cardiac parameters in elderly subjects suffering from mild cognitive impairment (MCI) or Alzheimer's disease (AD). METHODS: Two hundred and twenty-four community-living elderly subjects, 31 AD patients, 77 MCI patients, and 116 cognitively normal subjects (CNS), were evaluated for cognitive abilities (Mini Mental State Examination score (MMSE)) and for electrocardiographic [corrected heart rate QT interval dispersion (QTcD)] and echocardiographic [Left ventricular ejection fraction (LVEF)] parameters. RESULTS: Mean values of LVEF were not significantly different between the three groups; QTcD mean values were significantly lower in CNS group than in subjects with MCI and AD. The Pearson Product Moment Correlation test, carried out in the three study groups, showed a significant inverse correlation between QTcD and MMSE score (r = -0.357; p < 0.01) in the group of MCI patients, only. In multivariable-adjusted linear regression tests, QTcD (p = 0.030) and education (p = 0.021) are associated with MMSE score in MCI group. Only the parameter of education appears to predict MMSE in CNS group; none of these parameters appear to predict MMSE in the group of patients with AD. CONCLUSION: The association between QTcD and MMSE requires cautious interpretation and further extensive investigation. However, if confirmed by longitudinal studies, the finding could play a role in the management of the subjects with MCI.

Effect of the mandatory vaccination law on measles and rubella incidence and vaccination coverage in Italy (2013-2019).

Despite the introduction of the trivalent vaccine (measles, mumps, rubella) more than 20 years ago, measles outbreaks have occurred in Europe, including Italy, due to its underutilization. In Italy mandatory vaccination was established in 2017 (Decree Law 119/2017). This study aimed at evaluating the impact of mandatory vaccination and determining the trend in vaccination coverage for measles and rubella in Italy. We retrieved data from the Annual Status Update, a form sent annually by the Italian National Verification Committee to the Regional Verification Committee for Europe, from 1st January 2013 to 31st December 2019. Since the beginning of 2013, 14,788 cases of measles have been reported, ranging from 256 (3.9 x 1,000,000) to 5,397 (88.4 x 1,000,000) compared to 259 rubella cases for the same period. From 2013 to 2015, vaccination coverage decreased for the first dose of measles (90.4% to 85.3%) and rubella vaccine (90.3% to 85.2%), but then it increased significantly, reinforced by the Italian Decree Law, reaching 94.4% in 2019. The trend for the second dose showed a decrease from 2013 to 2016 (84.1% to 82.2% for measles and 83.7% to 82.0% for rubella), but then increased significantly and reached 90.2% in 2019 for measles and 90.0% for rubella. The mandatory vaccination law has resulted in a significant increase in vaccination coverage for measles and rubella in Italy, and demonstrates encouraging progress toward the 95% target and the restriction of measles transmission. Special attention should be paid to maintaining and further improving vaccination coverage.

Measles among healthcare workers in Italy: is it time to act?

Vaccination of healthcare workers (HCWs) against measles is strongly recommended in Europe. In this study, we examined the impact of measles on Italian HCWs by systematically and quantitatively analyzing measles cases involving HCWs over time and by identifying the epidemiological characteristics of the respective measles outbreaks. We retrieved data on measles cases from the Italian national integrated measles and rubella surveillance system from January 2013 to May 2019. Additionally, we performed a systematic review of the literature and an analysis of the measles and rubella aggregate outbreaks reporting forms from 2014 to 2018. Our review suggests that preventing measles infection among HCWs in disease outbreaks may be crucial for the elimination of measles in Italy. National policies aiming to increase HCW immunization rates are fundamental to the protection of HCWs and patients, will limit the economic impact of outbreaks on the institutions affected and will help achieve the elimination goal.

Knowledge and attitudes on pediatric vaccinations and intention to vaccinate in a sample of pregnant women from the City of Rome.

BACKGROUND: In recent years, pediatric immunization rates in Italy have decreased well below the recommended thresholds, largely due to an increase in scepticism about the efficacy and safety of vaccines. We aimed to identify the degree of such scepticism, and the factors driving it, among a sample of pregnant women in the City of Rome. METHODS: We conducted a cross-sectional survey on a sample of pregnant women attending antenatal classes (CANs) in Rome through distribution of a self-administered questionnaire. Multiple logistic regression models were built to analyze the determinants of knowledge, attitudes and intention to vaccinate in this population. RESULTS: A total of 458 pregnant women attending CANs in 36 family health centers and two hospitals in Rome answered the survey. Mean age was 32.9 (±5.0) years, and over 90% of women were in their first pregnancy. More than 26% of respondents showed a good level of knowledge of the safety and efficacy of vaccines, but there were high rates of uncertainty or agreement with some of the most common anti-vaccination sentiments. Only 75% of women were sure about vaccinating their children with the hexavalent vaccine, and 64.3% with MMR. A good level of knowledge was the strongest predictor of positive attitudes towards vaccination (OR 11.61, 95% CI 6.43-20.96), which, in turn, influenced the intention to vaccinate for most vaccines with the perception of the benefit of immunization for protection against disease. CONCLUSIONS: Scepticism about the safety, efficacy and importance of vaccines is associated to pregnant women's hesitancy to vaccinate their children, suggesting the need to develop strategies to increase vaccine acceptance in the antenatal period. The capacity of health care professionals, particularly midwives, to correctly deliver information to future parents should be strengthened in order to reduce the spread of misinformation and fear of vaccine safety.

Current Genetic Service Delivery Models for the Provision of Genetic Testing in Europe: A Systematic Review of the Literature.

Background: The provision of genetic services, along with research in the fields of genomics and genetics, has evolved in recent years to meet the increasing demand of consumers interested in prediction of genetic diseases and various inherited traits. The aim of this study is to evaluate genetic services in order to identify and classify delivery models for the provision of genetic testing in European and in extra-European countries. Methods: A systematic review of the literature was conducted using five electronic resources. Inclusion criteria were that studies be published in English or Italian during the period 2000-2015 and carried out in European or extra-European countries (Canada, USA, Australia, or New Zealand). Results: 148 genetic programs were identified in 117 articles and were delivered mostly in the UK (59, 40%), USA (35, 24%) or Australia (16, 11%). The programs were available nationally (66; 45%), regionally (49; 33%) or in urban areas (21, 14%). Ninety-six (64%) of the programs were integrated into healthcare systems, 48 (32.21%) were pilot programs and five (3%) were direct-to-consumer genetic services. The genetic tests offered were mainly for BRCA1/2 (59, 40%), Lynch syndrome (23, 16%), and newborn screening (18, 12%). Healthcare professionals with different backgrounds are increasingly engaged in the provision of genetic services. Based on which healthcare professionals have prominent roles in the respective patient care pathways, genetic programs were classified into five models: (i) the geneticists model; (ii) the primary care model; (iii) the medical specialist model; (iv) the population screening programs model; and (v) the direct-to-consumer model. Conclusions: New models of genetic service delivery are currently under development worldwide to address the increasing demand for accessible and affordable services. These models require the integration of genetics into all medical specialties, collaboration among different healthcare professionals, and the redistribution of professional roles. An appropriate model for genetic service provision in a specific setting should ideally be defined according to the type of healthcare system, the genetic test provided within a genetic program, and the cost-effectiveness of the intervention. Only applications with proven efficacy and cost-effectiveness should be implemented in healthcare systems and made available to all citizens.

Towards elimination of measles and rubella in Italy: Progress and challenges.

INTRODUCTION: In the WHO European Region, endemic transmission of measles and rubella had been interrupted by 37 and 42 of the 53 member states (MSs), respectively, by 2018. Sixteen MSs are still endemic for measles, 11 for rubella and nine for both diseases, the latter including Italy. Elimination is documented by each country's National Verification Committee (NVC) through an annual status update (ASU). OBJECTIVE: By analysing data used to produce the ASUs, we aimed to describe the advances made by Italy towards elimination of measles and rubella. Moreover, we propose a set of major interventions that could facilitate the elimination process. METHODS: A total of 28 indicators were identified within the six core sections of the ASU form and these were evaluated for the period 2013-2018. These indicators relate to the incidence of measles/rubella; epidemiological investigation of cases; investigation of outbreaks; performance of the surveillance system; population immunity levels; and implementation of supplemental immunization activities (SIAs). RESULTS: From 2013 to 2018, epidemiological and laboratory analyses of measles cases in Italy improved substantially, allowing timely investigation in 2017 and 2018 of most outbreak and sporadic cases and identification of the majority of genotypic variants. Moreover, since 2017, vaccination coverage has increased significantly. Despite these improvements, several areas of concern emerged, prompting the following recommendations: i) improve outbreak monitoring; ii) strengthen the MoRoNet network; iii) increase the number of SIAs; iv) reinforce vaccination services; v) maintain regional monitoring; vi) design effective communication strategies; vii) foster the role of general practitioners and family paediatricians. CONCLUSIONS: The review of national ASUs is a crucial step to provide the NVC with useful insights into the elimination process and to guide the development of targeted interventions. Against this background, the seven recommendations proposed by the NVC have been shared with the Italian Ministry of Health and the Technical Advisory Group on measles and rubella elimination and have been incorporated into the new Italian Elimination Plan 2019-2023 as a technical aid to facilitate the achievement of disease elimination goals.

Regional reports for the subnational monitoring of measles elimination in Italy and the identification of local barriers to the attainment of the elimination goal.

Although most countries in the WHO European Region were verified in 2017 as having interrupted endemic measles transmission, nine countries were still endemic. Among these, Italy accounted for the second highest number of measles cases reported in Europe in 2017. The elimination of measles is verified at national level by each country's National Verification Committee (NVC) through the production of an Annual Status Update (ASU). Since in Italy decentralization has led to an inhomogeneous implementation of immunization strategies among the 21 administrative Regions, the Italian NVC proposed that measles elimination should also be documented at the subnational level through regional ASUs and Synthetic Regional Reports (SRRs). The regional ASUs and the SRRs for 2014, 2015 and 2016 were produced and appraised by the NVC to evaluate the Regions' performances in each individual year as well as over the whole period. A specific analysis of vaccination coverage, including official immunization data for 2017, was performed. Moreover, the measles epidemic of 2017 was examined. Firstly, in the period 2014-2016, low immunization rates were registered in most Regions. Sixty-three per cent of southern Regions reported rates below the national mean and an overall low-quality performance. The approval of Italy's mandatory vaccination law in 2017 resulted in a marked increase in vaccination coverage; however, this increase was not homogeneous among Regions. Secondly, more than 50% of Regions did not report any supplemental immunization activity (SIA) for the period 2014-2016. Thirdly, from 2014 to 2016, fewer than one-third of Regions improved their reporting of outbreaks. Finally, over the study period, only two Regions reached the target required by the WHO for measles laboratory investigations. In countries with decentralized health policies, subnational monitoring can help identify local barriers to measles elimination. In Italy it has highlighted the need for further SIAs and a stronger surveillance system.

Identification of Delivery Models for the Provision of Predictive Genetic Testing in Europe: Protocol for a Multicentre Qualitative Study and a Systematic Review of the Literature.

INTRODUCTION: The appropriate application of genomic technologies in healthcare is surrounded by many concerns. In particular, there is a lack of evidence on what constitutes an optimal genetic service delivery model, which depends on the type of genetic test and healthcare context considered. The present project aims to identify, classify, and evaluate delivery models for the provision of predictive genetic testing in Europe and in selected Anglophone extra-European countries (the USA, Canada, Australia, and New Zealand). It also sets out to survey the European public health community's readiness to incorporate public health genomics into their practice. MATERIALS AND EQUIPMENT: The project consists of (i) a systematic review of published literature and selected country websites, (ii) structured interviews with health experts on the genetic service delivery models in their respective countries, and (iii) a survey of European Public Health Association (EUPHA) members' knowledge and attitudes toward genomics applications in clinical practice. The inclusion criteria for the systematic review are that articles be published in the period 2000-2015; be in English or Italian; and be from European countries or from Canada, the USA, Australia, or New Zealand. Additional policy documents will be retrieved from represented countries' government-affiliated websites. The results of the research will be disseminated through the EUPHA network, the Italian Network for Genomics in Public Health (GENISAP), and seminars and workshops. EXPECTED IMPACT OF THE STUDY ON PUBLIC HEALTH: The transfer of genomic technologies from research to clinical application is influenced not only by several factors inherent to research goals and delivery of healthcare but also by external and commercial interests that may cause the premature introduction of genetic tests in the public and private sectors. Furthermore, current genetic services are delivered without a standardized set of process and outcome measures, which makes the evaluation of healthcare services difficult. The present study will identify and classify delivery models and, subsequently, establish which are appropriate for the provision of predictive genetic testing in Europe by comparing sets of process and outcome measures. In this way, the study will provide a basis for future recommendations to decision makers involved in the financing, delivery, and consumption of genetic services.

Modification of the enantioselectivity of two homologous thermophilic carboxylesterases from Alicyclobacillus acidocaldarius and Archaeoglobus fulgidus by random mutagenesis and screening.

The esterase genes est2 from Alicyclobacillus acidocaldarius and AF1716 from Archaeoglobus fulgidus were subjected to error-prone PCR in an effort to increase the low enantioselectivity of the corresponding enzymes EST2 and AFEST, respectively. The model substrate ( RS)- p-nitrophenyl-2-chloropropionate was chosen to produce ( S)-2-chloropropionic acid, an important intermediate in the synthesis of some optically pure compounds, such as the herbicide mecoprop. In the case of EST2, a single mutant, Leu212Pro, was obtained showing a slightly enhanced preference toward the ( S) substrate; in the case of AFEST, a double mutant, Leu101Ile/Asp117Gly, was obtained showing an increased preference in the opposite direction. The 3-D structures of the EST2 and AFEST enzymes were analyzed by molecular modeling to determine the effects of the mutations. Mutations were positioned differently in the structures, but in both cases caused small modifications around the active site and in the oxyanion loop.