[Evaluation of the indirect impact of the Sars-CoV-2 epidemic on primary and ambulatory care processes using synthetic quality measures and graphic representations.] / Valutazione dell'impatto indiretto dell'epidemia da Sars-CoV-2 sui processi assistenziali del territorio attraverso rappresentazioni sintetiche della qualità delle cure.

INTRODUCTION: A concise representation of different primary and ambulatory care quality indicators can be very useful for quickly understanding the data and defining appropriate intervention strategies. The objectives of this study are to implement a graphical representation based on the TreeMap, a tool capable of summarizing results from heterogeneous indicators, with different measurement scales and thresholds, and take advantage of TreeMap's potential to measure the indirect impact of the Sars-CoV-2 epidemic on primary and ambulatory care processes. METHODS: Seven healthcare areas were considered each defined by a set of different indicators representative of the area. A discrete score ranging from 1 (very high quality) to 5 (very low quality) was assigned to the value of each indicator, based on the level of adherence to evidence-based recommendations. Finally, the score of each healthcare area is obtained as the weighted average of the scores of the representative indicators. The TreeMap is calculated for each Local health authority (Lha) of the Lazio Region. In order to assess the impact of the epidemic, a comparison was made between the results observed in 2019 and those observed in 2020. RESULTS: As an example, the results of one of the 10 Lhas of the Lazio Region have been reported. Compared to 2019, in 2020 there was an improvement in primary and ambulatory healthcare regarding all of the evaluated areas, with the exception of the metabolic area which remained stable. "Avoidable" hospitalizations have decreased, such as those for heart failure, Copd and diabetes. The incidence of cardio-cerebrovascular events following myocardial infarction or ischemic stroke has decreased, and inappropriate visits to emergency room have reduced. Furthermore, after decades of overprescribing, the use of drugs with a high risk of inappropriateness, such as antibiotics and aerosolized corticosteroids, has significantly decreased. DISCUSSION: The TreeMap has proven to be a valid tool for evaluating the quality of primary care, summarizing evidence from different and heterogeneous indicators. The improvements in quality levels observed in 2020, compared to 2019, should be interpreted with extreme caution because they could represent a paradox generated by the indirect effects of the Sars-CoV-2 epidemic. If, in the case of the epidemic, the distorting factors can be easily identified, in different and more ordinary evaluative analyses the "research for the causes" could be much more complex.

Cerebrospinal Fluid Lactate and Glucose Levels as Predictors of Symptomatic Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a complex neurovascular syndrome with profound systemic effects associated with high rates of disability and mortality. Delayed cerebral ischemia (DCI), which encompasses all neurobiological events occurring in the subacute-late stage after aSAH, has a complex pathogenesis and can occur in the absence of instrumental vasospasm. Our aim was to assess the correlation between cerebrospinal fluid (CSF) lactate and glucose levels measured on the second or third day after aSAH with clinical deterioration caused by DCI and with 3-month functional outcome. METHODS: This prospective study included all aSAH patients admitted between January 2020 and December 2021 who underwent external ventricular drain placement and CSF lactate and glucose measurement. RESULTS: Among 133 aSAH patients, 48 had an external ventricular drain placed and early CSF lactate and glucose assessment. Independent predictors of symptomatic DCI were World Federation of Neurosurgical Societies grade IV-V (adjusted odds ratio [aOR] 25.8, 95% confidence interval [CI] 2.9-649.2, P = 0.012), elevated CSF glucose (aOR 28.8, 95% CI 3.3-775.2, P = 0.010), and elevated CSF lactate (aOR 14.7, 95% CI 1.9-205.7, P = 0.018). The only independent predictor of 3-month functional outcome was occurrence of symptomatic DCI (aOR 0.02, 95% CI 0.0-0.2, P = 0.01). CONCLUSIONS: Elevated CSF lactate and glucose levels in the first 3 days following aSAH were independent predictors of subsequent DCI-related neurological impairment; the presence of instrumental vasospasm was not significantly correlated with DCI after multivariate adjustment. CSF lactate and glucose monitoring may represent a point-of-care test, which could potentially improve prediction of subacute neurological worsening and guide therapeutic choices. Further research with larger prospective cohorts is warranted.

Incidence and Outcomes of SARS-CoV-2 Infection in Older Adults Living with Dementia: A Population-Based Cohort Study.

BACKGROUND: The identification of risk factors for SARS-CoV-2 infection and mortality in patients with dementia is a key aspect to support clinical decisions and public health interventions. OBJECTIVE: To assess the incidence of SARS-CoV-2 infection and COVID-19 related death in a cohort of patients with dementia residing in the Lazio region and to investigate predicting factors for both infection and mortality. METHODS: This population-based study used information from administrative databases and the SARS-CoV-2 infection surveillance system. Patients with dementia (age ≥65) were enrolled as of December 31, 2019 and followed-up until February 28, 2021. Cumulative risk of infection and death within 60 days of infection onset, and age-standardized incidence (SIR) and mortality (SMR) ratios were calculated. Logistic regression models were applied to identify factors associated with infection and mortality. RESULTS: Among 37,729 dementia patients, 2,548 had a diagnosis of SARS-CoV-2 infection. The crude risk of infection was 6.7%. An increase in risk of infection was observed both in women (SIR 1.72; 95% CI 1.64-1.80) and men (SIR 1.43; 95% CI 1.33-1.54). Pneumonia, cerebrovascular and blood diseases, femur fracture, anxiety, antipsychotic and antithrombotic use were associated with an increased risk of infection. The crude risk of death was 31.0%, the SMRs 2.32 (95% CI 2.05-2.65) for men, and 2.82 (95% CI 2.55-3.11) for women. Factors associated with mortality included: male gender, age ≥85, symptoms at the diagnosis, antipsychotic and systemic antibiotics treatment. CONCLUSION: These findings emphasize the need of close and tailored monitoring of dementia patients to reduce the impact of COVID-19 on this fragile population.

[Geocoding one million of addresses using API: a semiautomatic multistep procedure]. / Geocodificare un milione di indirizzi mediante l'utilizzo di API: una procedura semiautomatica a più step.

OBJECTIVES: to geocode all residence addresses from Lazio Health Information System in order to obtain a geographical regional database. DESIGN: a semiautomatic and multistep geocoding procedure using several tools and software. SETTING AND PARTICIPANTS: all residence addresses of resident population of Lazio Region (Central Italy) in 2020. MAIN OUTCOME MEASURES: geographic coordinates at residence addresses and accuracy level of geocoding procedure for more than 1 million of addresses. RESULTS: the 99% of residence addresses in the Lazio Region have been geocoded thanks to the purposed procedure; almost 94% of the addresses have been geocoded with a good level of accuracy (more than 56% at civic number level). In the province of Rome, the percentage of addresses geocoded with a good level of accuracy is higher (97.1%), while in the province of Rieti and Frosinone is lower (82.7% and 84.2%, respectively). CONCLUSIONS: this method is useful to obtain accurate geographic coordinates of residences of the entire regional population. This database will be useful for several epidemiological studies in the Region.

Educational Inequalities in COVID-19 Vaccination: A Cross-Sectional Study of the Adult Population in the Lazio Region, Italy.

Several studies reported socioeconomic inequalities during the COVID-19 pandemic. We aimed at investigating educational inequalities in COVID-19 vaccination on 22 December 2021. We used the cohort of all residents in the Lazio Region, Central Italy, established at the beginning of the pandemic to investigate the effects of COVID-19. The Lazio Region has 5.5 million residents, mostly distributed in the Metropolitan Area of Rome (4.3 million inhabitants). We selected those aged 35 years or more who were alive and still residents on 22 December 2021. The cohort included data on sociodemographic, health characteristics, COVID-19 vaccination (none, partial, or complete), and SARS-CoV-2 infection. We used adjusted logistic regression models to analyze the association between level of education and no vaccination. We investigated 3,186,728 subjects (54% women). By the end of 2021, 88.1% of the population was fully vaccinated, and 10.3% were not vaccinated. There were strong socioeconomic inequalities in not getting vaccinated: compared with those with a university degree, residents with a high school degree had an odds ratio (OR) of 1.29 (95% confidence interval, CI, 1.27-1.30), and subjects with a junior high or primary school attainment had an OR = 1.41 (95% CI: 1.40-1.43). Since a comprehensive vaccination against COVID-19 could help reduce socioeconomic inequalities raised with the pandemic, further efforts in reaching the low socioeconomic strata of the population are crucial.

Prevention and contrast of child abuse and neglect in the practice of European paediatricians: a multi-national pilot study.

BACKGROUND: Child abuse and neglect, or maltreatment, is a serious public health problem, which may cause long-term effects on children's health and wellbeing and expose them to further adulthood vulnerabilities. Studies on child maltreatment performed in Europe are scarce, and the number of participants enrolled relatively small. The aim of this multi-national European pilot study, was to evaluate the level of understanding and perception of the concepts of child abuse and neglect by European paediatricians working in different medical settings, and the attitude toward these forms of maltreatment in their practice. METHODS: The study was performed by a cross-sectional, descriptive, online survey, made available online to European paediatricians members of 50 national paediatric, who belonged to four different medical settings: hospital, family care, university centres and private practice. The questionnaire, designed as a multiple choice questions survey, with a single answer option consisted of 22 questions/statements. Frequency analyses were applied. Most of the data were described using univariate analysis and Chi-squared tests were used to compare the respondents and answers and a significance level of p ≤ 0.05 applied. RESULTS: Findings show that European paediatricians consider the training on child maltreatment currently provided by medical school curricula and paediatric residency courses to be largely insufficient and continuing education courses were considered of great importance to cover educational gaps. Physical violence was recognized by paediatricians mostly during occasional visits with a significant correlation between detecting abuse during an occasional visit and being a primary care paediatrician. Results also showed a reluctance by paediatricians to report cases of maltreatment to the competent judicial authorities. CONCLUSIONS: Data of this study may provide useful contribution to the current limited knowledge about the familiarity of European paediatricians with child maltreatment and their skills to recognize, manage and contrast abusive childhood experiences in their practice. Finally, they could provide local legislators and health authorities with information useful to further improve public health approaches and rules able to effectively address shared risk and protective factors, which could prevent child abuse and neglect from ever occurring.

Impact of the COVID-19 pandemic on access to healthcare services amongst patients with multiple sclerosis in the Lazio region, Italy.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is a complex chronic, autoimmune inflammatory disease involving multidisciplinary assessments and interventions. Access to outpatient specialist and home healthcare services was explored during the pandemic outbreak and the lockdown amongst MS patients in the Lazio region. Adherence to disease-modifying therapies (DMTs) is also described. METHODS: A population-based study was conducted using regional healthcare administrative databases. A validated algorithm was used to identify MS cases over the period 2011-2018. The numbers of specialist and home-based services were compared between 2019 and 2020. The medication possession ratio was used to measure adherence to DMTs. RESULTS: A total of 9380 MS patients were identified (68% women). A decline in the number of outpatient care services between March and June 2020 compared to the previous year was observed, in particular for rehabilitation (-82%), magnetic resonance imaging (-56%) and neurological specialist services (-91%). Important year-to-year variations were observed in May and June 2020 in home-based nursing and medical care (-91%) and motor re-education services (-74%). Adherence to DMTs was higher in the first 4 months of 2019 compared to the same period of 2020 (67.1% vs. 57.0%). CONCLUSIONS: A notable disruption of rehabilitative therapy and home-based services as well as in DMT adherence was observed. Since the pandemic is still ongoing and interruption of healthcare services could have a major impact on MS patients, it is necessary to monitor access of MS patients to healthcare resources in order to ensure adequate treatments, including rehabilitative therapies.

[The health determinants in young children: testing a new surveillance system in Italy]. / I determinanti di salute nella prima infanzia: la sperimentazione di un nuovo sistema di sorveglianza in Italia.

In recent years, the scientific community has stressed the need to invest in the first 1,000 days of life - the time spanning between conception and the 2nd birthday - because it is during this period that the foundations of health are laid and whose effects will be present throughout the life and may influence the next generation. Taking this into account, in 2013 the National Centre for Disease Prevention and Control (CCM) of the Italian Ministry of Health promoted and financed a project to test a surveillance system of the main determinants of health concerning the child between the conception period and the 2nd years of life which are included in the National Programme "GenitoriPiù": folic acid before and during pregnancy, abstention from tobacco and alcohol during pregnancy and lactation, breastfeeding, infant sleep position, vaccination attitude, and early reading. The Project, started in January 2014 and ended in August 2016, has piloted the design, testing, and evaluation of the surveillance system with the view to national extension and the repeatability over time. The surveillance system has been designed to collect data through a questionnaire compiled by mothers in vaccination centres, in order to produce indicators which will enable territorial and intertemporal comparisons to be made. The project has shown the feasibility of this system, identifying favourable conditions and possible difficulties, and its ability to collect important information on children's health.

Process development of a human recombinant diabody expressed in E. coli: engagement of CD99-induced apoptosis for target therapy in Ewing's sarcoma.

Ewing's sarcoma (EWS) is the second most common primary bone tumor in pediatric patients characterized by over expression of CD99. Current management consists in extensive chemotherapy in addition to surgical resection and/or radiation. Recent improvements in treatment are still overshadowed by severe side effects such as toxicity and risk of secondary malignancies; therefore, more effective strategies are urgently needed. The goal of this work was to develop a rapid, inexpensive, and "up-scalable" process of a novel human bivalent single-chain fragment variable diabody (C7 dAbd) directed against CD99, as a new therapeutic approach for EWS. We first investigated different Escherichia coli constructs of C7 dAbd in small-scale studies. Starting from 60 % soluble fraction, we obtained a yield of 25 mg C7 dAbd per liter of bacterial culture with the construct containing pelB signal sequence. In contrast, a low recovery of C7 dAbd was achieved starting from periplasmic inclusion bodies. In order to maximize the yield of C7 dAbd, large-scale fermentation was optimized. We obtained from 75 % soluble fraction 35 mg C7 dAbd per L of cell culture grown in a synthetic media containing 3 g/L of vegetable peptone and 1 g/L of yeast extract. Furthermore, we demonstrated the better efficacy of the cell lysis by homogenization versus periplasmic extraction, in reducing endotoxin level of the C7 dAbd. For gram-scale purification, a direct aligned two-step chromatography cascade based on binding selectivity was developed. Finally, we recovered C7 dAbd with low residual process-related impurities, excellent reactivity, and apoptotic ability against EWS cells.

Blocking monocyte transmigration in in vitro system by a human antibody scFv anti-CD99. Efficient large scale purification from periplasmic inclusion bodies in E. coli expression system.

Migration of leukocytes into site of inflammation involves several steps mediated by various families of adhesion molecules. CD99 play a significant role in transendothelial migration (TEM) of leukocytes. Inhibition of TEM by specific monoclonal antibody (mAb) can provide a potent therapeutic approach to treating inflammatory conditions. However, the therapeutic utilization of whole IgG can lead to an inappropriate activation of Fc receptor-expressing cells, inducing serious adverse side effects due to cytokine release. In this regard, specific recombinant antibody in single chain variable fragments (scFvs) originated by phage library may offer a solution by affecting TEM function in a safe clinical context. However, this consideration requires large scale production of functional scFv antibodies and the absence of toxic reagents utilized for solubilization and refolding step of inclusion bodies that may discourage industrial application of these antibody fragments. In order to apply the scFv anti-CD99 named C7A in a clinical setting, we herein describe an efficient and large scale production of the antibody fragments expressed in E. coli as periplasmic insoluble protein avoiding gel filtration chromatography approach, and laborious refolding step pre- and post-purification. Using differential salt elution which is a simple, reproducible and effective procedure we are able to separate scFv in monomer format from aggregates. The purified scFv antibody C7A exhibits inhibitory activity comparable to an antagonistic conventional mAb, thus providing an excellent agent for blocking CD99 signaling. This protocol can be useful for the successful purification of other monomeric scFvs which are expressed as periplasmic inclusion bodies in bacterial systems.

Isolation of a new human scFv antibody recognizing a cell surface binding site to CEACAM1. Large yield production, purification and characterization in E. coli expression system.

The CEACAM1 cell adhesion molecule has recently received considerable interest as a tumour target antigen since its re-expression often occurs in the advanced stages of multiple malignancies including malignant melanoma, non-small cell lung cancer and other types of solid tumors. In this study, we describe the expression-purification and characterization of the new single chain variable fragment (scFv) antibody named DIATHIS1, that recognizes the N-terminal IgV-like domain present in CEACAM1. Three validation batches show that the production process is robust and reproducible. The scFv DIATHIS1 is formulated as a naturally occurring mixture of monomer and dimer. The antibody is biophysically stable at low temperature (-80°C), different concentrations and remains biologically active for at least 24months. The thermal stability of scFv DIATHIS1 at 37°C shows important features for its activity in vivo. The dimer behaves as a reservoir converting slowly into monomer. The monomer and dimer forms of scFv DIATHIS1 were isolated and characterized, showing high reactivity for CEACAM1. This new composition of antibody could have advantageous pharmacokinetics parameters over conventional scFv for in vivo applications.

Young-adult carriers of Neisseria meningitidis in Puglia (Italy): will the pattern of circulating meningococci change following the introduction of meningococcal serogroup C conjugate vaccines?

Studies of meningococcal carriage are essential in improving knowledge of the epidemiology of meningococcal disease. The aim of this study is to ascertain the carrier rate and the serogroups of Neisseria Meningitidis circulating in a sample of students from the University of Bari. The population consisted of university students from the University of Bari - School of Medicine, who were invited to take a nasopharyngeal swab. The swabs were plated on selective plate medium; cultural and MLST tests were performed. Of 583 university students 12 carriers were identified (2%). 9 isolates proved auto-agglutinable. The other strains belonged to serogroups B, W135 and Y. Auto-agglutinable strains belonged to different clonal complexes, of which ST-53 was the most common. Only one strain, that belonged to ST-23/cluster A3 clonal complex, could cause meningococcal disease. No type C serogroup strain was detected and this could be directly related to immunization policies that provided meningococcal serogroup C conjugate vaccines for newborns and adolescents. The changing pattern of circulating serogroups of Neisseria meningitidis in healthy carriers could support a new immunization strategy which could provide quadrivalent meningococcal conjugate vaccines to pre-adolescents and adults.

High level immunity against poliomyelitis in African and Asian refugees in southern Italy.

The aim of this study was to evaluate the level of poliomyelitis immunization in refugees residing in the Asylum Seeker Center in Bari. The study was carried out during 2008 and involved 573 refugees. An antibody titer >or=1:8 was found in 99.6% for poliovirus 1, in 99.8% for poliovirus 2, and in 99.5% for poliovirus 3.

Simultaneous administration of vaccines in immunization protocols: an audit in healthcare workers in the Puglia region of Italy.

Through a standardized questionnaire, this study investigated the opinions and attitudes of Vaccine Service staff in the Puglia Region of Italy regarding simultaneous administration of vaccines. Co-administration was practiced by 89.4%, and the staff's positive opinions were that it is important for work organization (80.8%) and as an opportunity to increase vaccine take-up (59.9%). Negative opinions were that it increases the risk of adverse reactions or undesired effects (11.3%) and can engender fear of such reactions in parents (31.1%).

[Risk factors for mortality during a heat-wave in Bari (Italy), summer 2005.]. / Fattori di rischio per la mortalità durante un'ondata di calore a Bari, estate 2005.

INTRODUCTION: The Italian Heat Health Watch Warning System (HHWWS) was set up following the over 3000 excess deaths which occurred in Italy during the heat wave of 2003, In June 2005 the warning system issued a heat warning in various Italian cities. METHODS: A case control study was performed in one of these cities (Bari) in order to identify individual and environmental risk factors as well as preventive strategies for reducing mortality during future heat waves. Cases were defined as subjects aged <65 years who had died during the heat wave and whose death certificate listed one of the following as the cause of death: heat, cardiovascular or cerebrovascular disorders, neurocognitive disorders, dehydration or fever/infection not otherwise specified. For each case, three age-matched controls were randomly selected among individuals followed by the same general practitioner as the case. All variables significantly associated with mortality (<0.1) in the univariate analysis were entered into a conditional logistic regression model and the population attributable fraction (PAF) was calculated for significant variables (at p<0.05). RESULTS: Twenty cases and sixty controls were included in the study. In 17 cases (89%) death had occurred at home and 11(55%) of these were cardiovascular- related deaths. At the multivariate analysis, the factors significantly associated with mortality risk during the heat wave were: having a functioning air conditioner at home [OR:0.09(95% CI 0.01-1.00)], having an Activities of Daily Living score <2 [OR:21.0(95%CI 1.81-242.47)] and having been hospitalized the year preceding death [OR:18.1(95%CI 2.04-160.51)]. CONCLUSIONS: Public health interventions during heat waves should include the provision of access to an air conditioned environment. Subjects with impaired health (especially if recently hospitalized) and with significant limitations in their activities of daily living are probably at higher risk during heat waves.