Screening program for latent tuberculosis infection in asylum seekers - a single center experience in Pavia, Italy.

BACKGROUND: The management of Latent Tuberculosis Infection is crucial in fighting Tuberculosis worldwide, and particularly in low incidence European Countries. While guidelines for the management of Tuberculosis in newly arrived immigrants have been issued by the European Center for Disease Control and Prevention and by the National Health Authorities in Italy, these are not widely implemented yet at local level. STUDY DESIGN: We report our program for the screening of Latent Tuberculosis Infection and active Tuberculosis in asylum seekers, jointly implemented by Public Health Authorities and the Infectious Diseases Department of a tertiary care, teaching hospital in Northern Italy. METHODS: We reviewed records of the asylum seekers who were screened at our center via Tuberculin Skin Test and/or Interferon Gamma Release Assay plus chest X-ray and either treated with Isoniazid Preventive Treatment or for active Tuberculosis Disease in case of positive results. RESULTS: We screened 726 migrants, mostly males (97.3%) and from Sub-Saharan Africa (82.2%) and found a high adherence rate for both screening (98.2%) and Isoniazid Preventive Treatment (90.1%). In addition, we found seven cases of active Tuberculosis. CONCLUSIONS: Latent Tuberculosis Infection screening and treatment proved feasible in our program, which should be systematically implemented in asylum seekers reaching Europe.

Immunological fingerprint of 4CMenB recombinant antigens via protein microarray reveals key immunosignatures correlating with bactericidal activity.

Serogroup B meningococcus (MenB) is a leading cause of meningitis and sepsis across the world and vaccination is the most effective way to protect against this disease. 4CMenB is a multi-component vaccine against MenB, which is now licensed for use in subjects >2 months of age in several countries. In this study, we describe the development and use of an ad hoc protein microarray to study the immune response induced by the three major 4CMenB antigenic components (fHbp, NHBA and NadA) in individual sera from vaccinated infants, adolescents and adults. The resulting 4CMenB protein antigen fingerprinting allowed the identification of specific human antibody repertoire correlating with the bactericidal response elicited in each subject. This work represents an example of epitope mapping of the immune response induced by a multicomponent vaccine in different age groups with the identification of protective signatures. It shows the high flexibility of this microarray based methodology in terms of high-throughput information and minimal volume of biological samples needed.

Multidisciplinary model for hospital-territory integrated management of patient with bone fragility: primary and secondary prevention of fractures according to severity and complexity.

The aim of this study was to promote the construction of a real network and a shared diagnostic and therapeutic management model between hospitals and out-of-hospital healthcare services to capture as many patients with bone fragility as possible. Starting from the analysis of the clinical competences present in the province of Pavia, the bone specialists (BSs) organized some educational events involving both general practitioners (GPs) and hospital specialists. The Fracture Liaison Service (FLS) model, the revision of Note 79, the national plan for chronicity and the health reform of the Lombardy Regional Authority supported the structure of our model, in which the roles of clinicians are well defined and based on the complexity and severity of patients. In our method the GP has a central role as clinical manager, facilitating patient management and communication between the specialists and the BS. In January 2019, the Therapeutic Care Diagnostic Path (PDTA) shared between 2 bone specialists (BSs), 9 GPs, as reference treaters, and a multidisciplinary group of 25 specialists of the Province of Pavia was defined. The strategic directions of the two largest public hospitals in Pavia have supported the PDTA, which was validated by the quality departments of the hospitals themselves. Finally, sixty GPs belonging to the network have joined the PDTA. This model is the first example of integrated management between hospitals and out-of-hospital healthcare services for the primary and secondary prevention of fragility fractures (FF), where the GPs play a pivotal role as managers and supervisors to ensure proper care to chronic patients according to their levels of severity.

Prevention of nosocomial legionellosis by best water management: comparison of three decontamination methods.

BACKGROUND: Since 2000, the National Health System has adopted international guidelines for assessing Legionella spp. in hospital water systems. The control of water contamination by Legionella spp. is still a matter of research concerning the most effective method in preventing nosocomial infections. AIM: To compare three different decontamination methods by monitoring colony-forming unit count and number of hospital-acquired legionellosis cases. A secondary objective was to evaluate the long-term effects of the preventive measures on the water pipes. METHODS: A protocol was developed for the selection of high-risk sampling sites and for the testing of three disinfection methods over the course of 19 years: hyperchlorination and thermal shock (period A, 2000-2005); copper-silver ionization (period B, 2006-2010); and integration of pre-filtering, filtering, pipe-protecting products, and remote control with chlorine dioxide (ClO2) (period C, 2011-2018). FINDINGS: The use of shock disinfection and hyperchlorination led to a decrease in contamination level immediately after the procedure, but then it rose again to the previous level in two months. Both copper-silver ionization and ClO2 disinfection showed a stable and durable decrease in contamination level. Throughout these three phases, six cases of Legionella spp. occurred during period A, six cases during period B, and three cases during period C. With regard to the damage of water pipes, effective copper-silver levels caused corrosion and calcification in water pipes. CONCLUSION: Both copper-silver ionization and ClO2 properly controlled Legionella spp. contamination. ClO2 significantly reduced the number of positive sites (P < 0.001) without damaging the pipelines.

Evaluation of a model to improve collection of blood cultures in patients with sepsis in the emergency room.

Sepsis begins outside of the hospital for nearly 80% of patients and the emergency room (ER) represents the first contact with the health care system. This study evaluates a project to improve collection of blood cultures (BCs) in patients with sepsis in the ER consisting of staff education and completion of the appropriate BC pre-analytical phase. A retrospective observational study performed to analyse the data on BC collection in the ER before and after a three-phase project. The first phase (1 January to 30 June 2015) before the intervention consisted of evaluation of data on BCs routinely collected in the ER. The second phase (1 July to 31 December 2015) was the intervention phase in which educational courses on sepsis recognition and on pre-analytical phase procedures (including direct incubation) were provided to ER staff. The third phase (1 January to 30 June 2016; after the intervention) again consisted of evaluation. Before the intervention, out of 24,738 admissions to the ER, 103 patients (0.4%) were identified as septic and had BCs drawn (359 BC bottles); 19 out of 103 patients (18.4%) had positive BCs. After the intervention, out of 24,702 admissions, 313 patients (1.3%) had BCs drawn (1,242 bottles); of these, 96 (30.7%) had positive BCs. Comparing the first and third periods, an increase in the percentage of patients with BCs collected (from 0.4% to 1.3% respectively, p < 0.0001) and an increase in the percentages of patients with true-positive BCs (from 0.08% to 0.39% of all patients evaluated respectively, p < 0.0001) were observed. The isolation of bacteria by BCs increased 3.25-fold after project implementation. These results can be principally ascribed to an improved awareness of sepsis in the staff associated with improved pre-analytical phase procedures in BC collection.

Public Health and Hospitals: a Common Area for Clinical and Public Health Medicine.

Contrary to what has happened so far, hospitals should become a setting which jointly exercise Clinical and Public Health Medicine. The areas of activity that require the presence of multidisciplinary teams and can bring benefits both to the patients and to the community is briefly described.

Different drug-resistant influenza A(H3N2) variants in two immunocompromised patients treated with oseltamivir during the 2011-2012 influenza season in Italy.

BACKGROUND: Monitoring the emergence of drug-resistant influenza variants is crucial in influenza surveillance programs. OBJECTIVES: Influenza A kinetics and the emergence of drug-resistant strains in hospitalized patients treated with oseltamivir were investigated. STUDY DESIGN: Sequential samples from oseltamivir-treated and -untreated hospitalized patients in the period November 2011 through April 2012 were analyzed. NA gene was sequenced in samples from oseltamivir treated patients. Clonal analysis of the viral population was performed in patients unresponsive to treatment. Viral kinetics was determined in 24 (14 immunocompromised and 10 immunocompetent) A(H3N2)-positive patients treated and 24 (10 immunocompromised and 14 immunocompetent) untreated patients. RESULTS: Viral shedding was significantly reduced in treated vs untreated immunocompromised patients (7 vs 22 days, p<0.05, respectively). Viral load decreased significantly in immunocompromised and immunocompetent treated patients as compared with immunocompromised and immunocompetent untreated patients (0.73 and 0.93 vs 0.47 and 0.45 log10/day, p<0.05). In two (8.3%) treated patients with prolonged virus shedding, the oseltamivir resistance R292K mutation was revealed. In these patients, clonal analysis of the virus population showed the presence of additional oseltamivir-resistant mutants (E119V, N294S and deletion Del247-250). CONCLUSIONS: Oseltamivir resistance is reported for the first time in A(H3N2) virus strains during the 2011-2012 influenza season. Different drug-resistant viruses emerged in hospitalized immunocompromised patients showing prolonged virus shedding.

Molecular and cellular signatures of human vaccine adjuvants.

Oil-in-water emulsions are potent human adjuvants used for effective pandemic influenza vaccines; however, their mechanism of action is still unknown. By combining microarray and immunofluorescence analysis, we monitored the effects of the adjuvants MF59 oil-in-water emulsion, CpG, and alum in the mouse muscle. MF59 induced a time-dependent change in the expression of 891 genes, whereas CpG and alum regulated 387 and 312 genes, respectively. All adjuvants modulated a common set of 168 genes and promoted antigen-presenting cell recruitment. MF59 was the stronger inducer of cytokines, cytokine receptors, adhesion molecules involved in leukocyte migration, and antigen-presentation genes. In addition, MF59 triggered a more rapid influx of CD11b+ blood cells compared with other adjuvants. The early biomarkers selected by microarray, JunB and Ptx3, were used to identify skeletal muscle as a direct target of MF59. We propose that oil-in-water emulsions are the most efficient human vaccine adjuvants, because they induce an early and strong immunocompetent environment at the injection site by targeting muscle cells.

[The health services epidemiology in health agency: the initiatives, the activities, the structures. Introduction to the subject]. / L'epidemiologia dei servizi sanitari nelle aziende sanitarie: le iniziative, le attività, le strutture. Introduzione al tema.

The subject which has been developed within the Workshop "the health services Epidemiology in health Agency: the initiatives, the activities, the structures. Direct and indirect evidences", held in Rome, in November 15th, 2001, is introduced and updated. After a historical excursus, the topical interest in the health services epidemiology, which has now assumed the aspect of a real, independent discipline, and the reasons for its development, are analysed. As an independent discipline, its typical methodology and function have to be recognised. The methodology is characterised by the wide use of qualitative methods, by the importance assigned to the secondary epidemiologic research (i.e. systematic reviews and meta-analysis) and by the particular interest devoted to evaluation rather than investigative surveys. The function is aimed at improving people's health by means of health care services and, as a practical consequence, useful to the former one, at improving the quality of health care services themselves.

[The District: the place of management of community health services or the place of governance of primary health care? The epidemiologic context]. / Il Distretto: luogo di gestione dei servizi territoriali o centrodi responsabilità dell'assistenza sanitaria primaria? Il contesto epidemiologico.

This is a review of epidemiologic requirements for the governance of District health services. The governance concern both the health system (organization, management and assessment of health services) and the population's health (health needs, health services needs, determinants of health).

Gene expression profile in Neisseria meningitidis and Neisseria lactamica upon host-cell contact: from basic research to vaccine development.

Differential gene regulation in the human pathogen Neisseria meningitidis group B (MenB) and in Neisseria lactamica, a human commensal species, was studied by whole genome microarray after bacterial interaction with epithelial cells. Host-cell contact induced changes in the expression of 347 and 285 genes in MenB and N. lactamica, respectively. Of these, only 167 were common to MenB and N. lactamica, suggesting that a different subset of genes is activated by pathogens and commensals. Change in gene expression was stable over time in N. lactamica, but short-lived in MenB. A large part (greater than 30%) of the regulated genes encoded proteins with unknown function. Among the known genes, those coding for pili, capsule, protein synthesis, nucleotide synthesis, cell wall metabolism, ATP synthesis, and protein folding were down-regulated in MenB. Transporters for iron, chloride and sulfate, some known virulence factors, GAPDH and the entire pathway of selenocysteine biosynthesis were upregulated. Gene expression profiling indicates that approximately 40% of the regulated genes encode putative surface-associated proteins, suggesting that upon cell contact Neisseria undergoes substantial surface remodeling. This was confirmed by FACS analysis of adhering bacteria using mouse sera against a subset of recombinant proteins. Finally, a few surface-located, adhesion-activated antigens were capable of inducing bactericidal antibodies, indicating that microarray technology can be exploited for the identification of new vaccine candidates.

Time-resolved experiments on light diffusion in anisotropic random media

Multiple light scattering in isotropic and anisotropic media is studied experimentally with an optical gating technique, as commonly used in fluorescence spectroscopy. The experimental setup permits an accurate analysis of the propagation of a short light pulse through disordered or partially ordered media. The diffusion constant of some isotropic systems is reported, and the anisotropy in the diffusion constant for light diffusion through liquid crystals is observed. For the time-resolved data, good agreement with diffusion theory is found in all cases, including the liquid crystal in the nematic phase.

Long-term effects of carvedilol in idiopathic dilated cardiomyopathy with persistent left ventricular dysfunction despite chronic metoprolol. The Heart-Muscle Disease Study Group.

OBJECTIVES: The purpose of this study was to analyze whether long-term treatment with the nonselective beta-adrenergic blocking agent carvedilol may have beneficial effects in patients with dilated cardiomyopathy (DCM), who are poor responders in terms of left ventricular (LV) function and exercise tolerance to chronic treatment with the selective beta-blocker metoprolol. BACKGROUND: Although metoprolol has been proven to be beneficial in the majority of patients with heart failure, a subset of the remaining patients shows long-term survival without satisfactory clinical improvement. METHODS: Thirty consecutive DCM patients with persistent LV dysfunction (ejection fraction < or =40%) and reduced exercise tolerance (peak oxygen consumption <25 ml/kg/min) despite chronic (>1 year) tailored treatment with metoprolol and angiotensin-converting enzyme inhibitors were enrolled in a 12-month, open-label, parallel trial and were randomized either to continue on metoprolol (n = 16, mean dosage 142+/-44 mg/day) or to cross over to maximum tolerated dosage of carvedilol (n = 14, mean dosage 74+/-23 mg/day). RESULTS: At 12 months, patients on carvedilol, compared with those continuing on metoprolol, showed a decrease in LV dimensions (end-diastolic volume -8+/-7 vs. +7+/-6 ml/m2, p = 0.053; end-systolic volume -7+/-5 vs. +6+/-4 ml/m2, p = 0.047), an improvement in LV ejection fraction (+7+/-3% vs. -1+/-2%, p = 0.045), a reduction in ventricular ectopic beats (-12+/-9 vs. +62+/-50 n/h, p = 0.05) and couplets (-0.5+/-0.4 vs. +1.5+/-0.6 n/h, p = 0.048), no significant benefit on symptoms and quality of life and a negative effect on peak oxygen consumption (-0.6+/-0.6 vs. +1.3+/-0.5 ml/kg/min, p = 0.03). CONCLUSIONS: In DCM patients who were poor responders to chronic metoprolol, carvedilol treatment was associated with favorable effects on LV systolic function and remodeling as well as on ventricular arrhythmias, whereas it had a negative effect on peak oxygen consumption.

[Possibilities and limitations of the predictive risk estimates and epidemiological studies following the Chernobyl incident]. / Possibilità e limiti di stime predittive di rischio e indagini epidemiologiche a seguito dell'incidente di Chernobyl.

The disastrous accident at the nuclear power station at the Chernobyl on 1986 (April 26) has brought attention to the estimation of radiation health effects and many "experts" were attending to the evaluation on oncogenic mortality increase among the Italian population in the next future. On the contrary at that time too few peoples were worried about the possibility of detecting such an increase. Discussion of this topic is notoriously fraught with difficulties arising from differences of opinion how to estimate low-dose risk in humans without data from direct observation. One opinion is to extrapolate from the data points obtained at relatively high doses toward zero dose (zero extrapolation theory). This permit estimates of risk to be made but, in the final analysis, no data from humans exist that show that low-level radiation exposures produce measurable biologic effects. For that this theory is more useful in radio-protection and medico-legal subjects. It is easy on a statistical basis to prove the impossibility to establish an increase in human cancer after low doses of ionizing radiation such as those received environmentally after the Chernobyl's accident. In this condition to observe the numbers of radiation-induced cancer deaths that far exceed the "natural" incidence would require a follow-up a sample more and more greater than the italian population herself. Indeed the statistical power of a hypothetical follow-up study at a suitable confidence level would require a sample size higher than a milliard of persons for the detection of an increase of a generic cancer mortality and higher then seven hundred of millions for the detection of an increase of the specific thyroid cancer mortality. In more detail the following figures for the parameters needed to curring out the evaluation have been used: medium dose equivalent to the thyroid, 2.03 mSv; medium effective dose equivalent up to december '87, 0.6 mSv; thyroid cancer mortality in the italian population, 0.94 10(-5) y-1; total cancer mortality in the italian population, 22.2 10(-2) y-1; risk factor per unit dose equivalent in thyroid, 0.5 10(-6) mSv-1; risk factor per unit effective dose equivalent, 2.0 10(-5) mSv-1. Applying the foregoing values in statistical inference methods it could be achieved that 7.5 18(8) and 1.25 10(9) persons must be followed-up in the next 30 years to detect a significant increase over the "natural" cancer mortality for thyroid and "total body" radioinduced cancers respectively.(ABSTRACT TRUNCATED AT 400 WORDS)