Universal Health Coverage in Italy: lights and shades of the Italian National Health Service which celebrated its 40th anniversary.

The Italian National Health Service (I-NHS) was established in 1978 to guarantee universal access to healthcare. Prominent in international reports, the I-NHS has reached a satisfactory level of efficiency and excellent standards of care in many regions, in forty years. Along the years, I-NHS has developed a structural public-private partnership in health services delivery that in some regions contributes to the achievement of very high standards of healthcare quality. However, the I-NHS is currently facing some major challenges: (a) Italy is experiencing a remarkable aging of its population with increasing health needs; (b) the recent and constant cuts to public expenditures are reducing the budget for welfare. It is of utmost importance to ensure that on-going efforts to contain health system costs do not subsume health care quality. In addition, monitoring of the essential levels of care (Livelli Essenziali di Assistenza, LEA) highlights significant differences in healthcare delivery among Italian regions that, in turns, contribute to the burdensome migration of patients to best-performing regions. Therefore, a more consolidated and ambitious approach to quality monitoring and healthcare improvement at a system level is needed to guarantee its sustainability in the future.

An overview of different health indicators used in the European Health Systems.

INTRODUCTION: In the European Union three different health systems could be defined according to service delivery, financing, and economic policies: Beveridge, Bismarck and Mixed system. Although health systems are hardly to compare, various organizations are developing methods assessing performance. In the present work the performance of the three systems were evaluated using European Community Health Indicators according to Organization for Economic Cooperation and Development. METHODS: The study has been conducted among the 28 states of the European Union using the following indicators: Standardized death rate for diseases of the circulatory system, standardized death rate of malignant neoplasms, road traffic accidents with injury, life expectancy at birth, incidence of Human Immunodeficiency Virus (HIV), infant deaths, pure alcohol consumption, infants vaccinated against Diphtheria Tetanus Pertussis (DTP), public and total expenditure on health over the period 2001-2010. RESULTS: The variation of health indicators over the observational time shows similar trend of circulatory system diseases and malignant neoplasms death rates, road accidents with injury, infant deaths, life expectancy at birth, public and total health expenditure. Some differences in the trend of HIV incidence, alcohol intake and DTP vaccination rates arise among systems. Grouping countries by health system paradigm and geographical area, resulted in a relevant heterogeneity (I2 ≥ 90%, Pvalue < 0.0001). No clear superiority of a given health delivery system was found with respect to other paradigms. CONCLUSIONS: In accordance with the evidence of our study, it can be stated that best performances are more likely to be linked to country specific economic factors. In conclusion, it was not possible to identify the best health system model.

What's growing on General Practitioner's stethoscope?

BACKGROUND: Non-critical medical devices, as stethoscopes, have long been considered as vectors in microorganisms' transmission. Cleaning standards for non-critical medical equipment are often unclear. This study was designed to assess the attitude of General Practitioners (GPs) towards cleaning their stethoscope and the degree of microbiological contamination of doctor's instrument in outpatient setting. STUDY DESIGN: Observational, crossover study. METHODS: A structured questionnaire was administered to GPs to test their knowledge about medical instrument's cleanliness recommendations and the surface of the diaphragm of their stethoscopes was analyzed for bacteriological isolates using mass spectrometry technique. RESULTS: Most of GPs declared they don't know cleaning recommendations for non-critical medical devices and a relevant bacterial growth was identified on the majority of the stethoscopes' membranes. Almost all microbiological isolates resulted typically found in cutaneous flora. CONCLUSIONS: We can't state that the GP's stethoscopes feature a risk of transmission for microbiological pathogens; anyway, because of the level of contamination we observed, cleaning recommendations to disinfect instruments on a regular basis should be better indicated.

Predictors of Ominous Outcome in Infants Undergone to Cardiac Surgery and Cardiopulmonary by-Pass: S100B Protein.

S100B protein has been recently proposed as a consolidated marker of brain damage and death in adult, children and newborn patients. The present study evaluates whether the longitudinal measurement of S100B at different perioperative time-points may be a useful tool to identify the occurrence of perioperative early death in congenital heart disease (CHD) newborns. We conducted a case-control study in 88 CHD infants, without pre-existing neurological disorders or other co-morbidities, of whom 22 were complicated by perioperative death in the first week from surgery. Control group was composed by 66 uncomplicated CHD infants matched for age at surgical procedure. Blood samples were drawn at five predetermined time-points before during and after surgery. In all CHD children, S100B values showed a pattern characterized by a significant increase in protein's concentration from hospital admission up to 24-h after procedure reaching their maximum peak (P<0.01) during cardiopulmonary by-pass and at the end of the surgical procedure. Moreover, S100B concentrations in CHD death group were significantly higher (P<0.01) than controls at all monitoring time-points. The ROC curve analysis showed that S100B measured before surgical procedure was the best predictor of perioperative death, among a series of clinical and laboratory parameters, reaching at a cut-off of 0.1 µg/L a sensitivity of 100% and a specificity of 63.7%. The present data suggest that in CHD infants biochemical monitoring in the perioperative period is becoming possible and S100B can be include among a series of parameters for adverse outcome prediction.

Effects of priming volume reduction on allogeneic red blood cell transfusions and renal outcome after heart surgery.

INTRODUCTION: Excessive hemodilution during cardiopulmonary bypass (CPB) is associated with an increased rate of red blood cell (RBC) transfusion and acute kidney injury (AKI). Minimization of the oxygenator priming volume is a measure to contain hemodilution. In this study, we evaluated the new oxygenator, Sorin Inspire 6™, with respect to its ability to limit hemodilution, RBC transfusion rate and postoperative AKI rate. METHODS: A retrospective study on a consecutive series of 1,724 adult patients receiving heart surgery with CPB. Patients treated with the Inspire 6™ were assigned to the low priming volume oxygenator (LPVO) group (N=383) and patients treated with conventional oxygenators to the conventional group (N=1,341). Dynamic priming volume, time course of the hematocrit, RBC transfusions and AKI rate were compared between the groups. RESULTS: Priming volume was significantly (p=0.001) lower in the LPVO group (624±113 mL) vs. the conventional group (775±150 mL), with higher values of hematocrit during and after CPB. After correction for other confounders, patients in the LPVO group had a significantly lower RBC transfusion rate (odds ratio 0.68, 95% confidence interval 0.52-0.90, p=0.006) and AKI rate (odds ratio 0.55, 95% confidence interval 0.32-0.93, p=0.032). CONCLUSION: The Inspire 6™ oxygenator allows a significant containment of hemodilution during CPB, reducing the risk of RBC transfusions and postoperative AKI.

The students' reasons to choose a nursing degree program: an Italian exploratory study.

BACKGROUND: From the international literature very interesting cues emerge about students' motivations to choose a Nursing Degree Program. Unfortunately, this phenomenon is largely unexplored in Italy. An observational study was conducted at the University of Pavia, with the aim to investigate the reasons underpinning the students' choice to enter a Nursing Degree Program. METHODS: A semi-structured, self-administrated questionnaire was used for this single-center cross-sectional study. The questionnaire was aimed to investigate the reasons underpinning the students' choice to enter a Nursing Degree Program, using both open-ended and close-ended multiple choice questions. Descriptive statistics have been used to describe collected data. Open-ended response analysis was conducted through an exploratory and qualitative analysis of language. RESULTS: Response rate was 71% (196/275). Our study results highlighted a variety of reasons that encourage students to begin a Nursing Degree Program: the feeling of usefulness (80%), the desire to help and to care people (78%), the interest in the sciences (71%), the compassion to the suffering people (66%). We also identified 4 categories that describe which characteristics a nurse should have according to the students' point of view: expertise; personal characteristics; to experience the professional life as a social function and to have interest in the health field. CONCLUSIONS: Students' answers indicate that often the choice to enter a Nursing Degree Program is not supported by clear ideas and strong motivations. We consider it crucial to provide a realistic image of the nursing role and opportunities for career development, so that students can have the right elements to make a conscious choice. There is a need for more qualitative research to explore the reasons why students choose the Nursing Degree Program; moreover, to identify, from the beginning of the course, those students who are in crisis of motivation, in order to adopt support strategies that could enable them to successfully achieve academic career.

Percentage hematocrit variation (PHEVAR) index as a quality indicator of patient blood management in cardiac surgery.

BACKGROUND: Severe hemodilution and perioperative bleeding are determinants of hematocrit (HCT) variations in cardiac surgery patients. These variations may be direct determinants of bad outcomes, and may trigger allogeneic blood product transfusions, which are associated with morbidity and mortality. The present study introduces the Percentage HEmatocrit VARiation (PHEVAR) index as a tool to assess the quality of patient blood management (PBM) and to possibly guide specific interventions. METHODS: Seven-hundred-thirteen adult cardiac surgery patients were included in a retrospective analysis. The PHEVAR index was assessed based on the HCT determination at six points in time, being represented by the area under the curve of the percentage HCT variation from baseline. The PHEVAR index was explored for association with operative mortality and other outcome measurements. RESULTS: The PHEVAR index was an independent predictor of operative mortality (odds ratio 1.015, 95% confidence interval 1.005-1.026), postoperative bleeding, length of mechanical ventilation; significantly higher values of PHEVAR were detected in patients with acute kidney injury, low cardiac output, and ventricular arrhythmias. Acute kidney injury was associated with a larger HCT variation during surgery; low cardiac output with a larger postoperative HCT variation; and ventricular arrhythmias with a larger preoperative HCT variation. CONCLUSION: The PHEVAR index reflects HCT variations during 7 days of hospital stay in cardiac surgery patients, is associated with mortality and morbidity, and may be used as a quality index for PBM.

Tricuspid annular plane systolic excursion and pulmonary arterial systolic pressure relationship in heart failure: an index of right ventricular contractile function and prognosis.

Echo-derived pulmonary arterial systolic pressure (PASP) and right ventricular (RV) tricuspid annular plane systolic excursion (TAPSE; from the end of diastole to end-systole) are of basic relevance in the clinical follow-up of heart failure (HF) patients, carrying two- to threefold increase in cardiac risk when increased and reduced, respectively. We hypothesized that the relationship between TAPSE (longitudinal RV fiber shortening) and PASP (force generated by the RV) provides an index of in vivo RV length-force relationship, with their ratio better disclosing prognosis. Two hundred ninety-three HF patients with reduced (HFrEF, n = 247) or with preserved left ventricular (LV) ejection fraction (HFpEF, n = 46) underwent echo-Doppler studies and N-terminal pro-brain-type natriuretic peptide assessment and were tracked for adverse events. The median follow-up duration was 20.8 mo. TAPSE vs. PASP relationship showed a downward regression line shift in nonsurvivors who were more frequently presenting with higher PASP and lower TAPSE. HFrEF and HFpEF patients exhibited a similar distribution along the regression line. Given the TAPSE, PASP, and TAPSE-to-PASP ratio (TAPSE/PASP) collinearity, separate Cox regression and Kaplan-Meier analyses were performed: one with TAPSE and PASP as individual measures, and the other combining them in ratio form. Hazard ratios for variables retained in the multivariate regression were as follows: TAPSE/PASP

RAGE gene polymorphism in heart failure patients with and without angiographic evidence of significant coronary atherosclerosis.

Heart failure (HF) is a multifactorial disorder in which clinical, environmental and genetic components take part. For this reason it is possible that common gene variants could affect development, progression and response to pharmacological therapy. In recent years the role of AGEs in the pathogenesis of cardiovascular diseases has become recognized but little is known about the role of the AGE–RAGE system in heart failure. The aim of the present study was to identify possible relationship between -374 T/A RAGE gene polymorphism with heart failure. The population in this study consists of 386 subjects with HF, selected according to the presence of depressed Left Ventricular Ejection Fraction (LVEF) less than45 percent, and 639 patients with CAD documented at coronary angiography. Within the population with HF there are 228 patients with disease secondary to not ischemic cause and 158 with post-ischemic condition. The sample of AA genotype was significantly lower in patients with post-ischemic HF in respect to HF secondary to non-ischemic causes (pless than0.001). A significant difference between the two groups was also observed regarding the allele frequency. In addition, differences in the allelic and the genotypic frequencies of homozygous genotypes were found between the HF patients free from evidence of coronary significant lesions and patients with at least one hemodynamically significant coronary lesion, both HF and CAD. In patients with at least one vessel compromised the presence of A allele and the homozygous AA genotype were significantly lower than in patients with lesion-free coronary. In conclusion, our research reveals that the -374 T/A polymorphism is related to the genesis of atherosclerotic coronary artery disease but not to its evolution. The protective role of AA genotype in respect to atheromatous disease is therefore confirmed also in the HF population with non-ischemic origin.

Prevention in the workplace and training of personnel: new methodological approaches.

In Italy since 15 years huge investments in term of human, material and economical resources have been allocated to prevention. However epidemiological data show unsatisfactory results. It's necessary and urgent to modify the general learning of prevention in order to increase all the actors involved in social and productive system. The aim of our project is to improve competencies and knowledge concerning hygiene in the workplace and prevention of nursing personnel, using cooperative-learning model, concerning the ways of transmission of infectious diseases, so that they will be able to develop their activities and being motivated in the adoption of safety proceedings. The results indicate, in all the participants groups, an improvement of their skills and knowledge about the correct behavioural procedures to limit biological hazards for themselves and for their patients. We observed increased motivation and awareness, a greater ability to take action when they see the adoption of inadequate or incorrect procedures by colleagues.

Galectin-3 plasma levels and coronary artery disease: a new possible biomarker of acute coronary syndrome.

Inflammation plays a key role in atherosclerosis. Galectin-3 is a macrophage- and endothelium-derived mediator actively involved in the regulation of many aspects of inflammatory cell behaviour. The aim of this study is to quantify plasma Galectin-3 in patients with coronary artery disease (CAD) and different clinical manifestation at the moment of observation in order to verify whether Galectin-3 could be a useful biomarker of atherosclerotic state. We enrolled 125 patients affected by CAD, angiographically documented (70 stable, 55 unstable). They underwent accurate examinations and anamnestic data was collected. The most important traditional risk factors, such as age, hypertension, and body mass index, were reported. Plasma Galectin-3 was quantified using an ELISA kit. Unstable patients (n = 55) had a higher plasma Galectin-3 levels in respect to the stable subjects (27.75 ng/mL (19.27-39.09) vs 6.48 ng/ml (4.88-8.83), p<0.001. A trend in correlation between plasma Galectin-3 levels and number of vessels compromised seems to be present: CAD patients with three-vessel disease had higher levels of Galectin-3 than patients with one-or two-vessel disease (17.39 ng/ml (10.75-29.82) vs 9.18 ng/ml (5.56-23.22), p= 0.058. The significantly higher plasma Galectin-3 levels in patients with unstable angina in respect to the stable angina confirm the involvement of Galectin-3 in promoting macrophage activation and monocyte attraction. Despite the distribution of CAD in patients with acute and chronic coronary disease being similar, we may hypothesize that Galectin-3 could be a useful biomarker of atherosclerotic plaque and in particular of its destabilization.

Apelin plasma levels predict arrhythmia recurrence in patients with persistent atrial fibrillation.

Low levels of the regulatory peptide apelin have been reported in patients with lone atrial fibrillation (AF). We evaluate the potential utility of assessing apelin plasma levels as a predictor of AF recurrence in individuals presenting for electrical cardioversion. Plasma levels of apelin, brain natriuretic peptide (BNP) and high-sensitivity C-reactive protein were measured in 93 patients, with persistent AF before successful external electrical cardioversion. Significantly lower apelin plasma levels were found in patients with AF recurrence as respect to population with persistence of sinus rhythm during a six months follow-up. The hazard increased with duration of AF, left atrial dimension, BNP concentrations. Subjects with apelin levels below the median had a hazard ratio of 3.1 of arrhythmia recurrence with respect to those with high apelin levels (p<0.05). A significant difference in BNP levels was found between patients with and without AF recurrence during the follow-up. After adjusting for potential confounders, both BNP and apelin retained their statistical significance as independent predictors of arrhythmia recurrence. Patients with both low apelin and elevated BNP had a worse prognosis compared with those with either low apelin or elevated BNP alone. Low plasma apelin levels before external electrical cardioversion are an independent prognostic factor for arrhythmia recurrence in patients with AF treated with antiarrhythmic drugs. Apelin may be of particular value for the identification of high-risk patients in addition to BNP.

Cell reprogramming: expectations and challenges for chemistry in stem cell biology and regenerative medicine.

The possibility of reprogramming adult somatic cells into pluripotent stem cells (iPSCs) has generated a renewed interest into stem cell research and promises to overcome several key issues, including the ethical concerns of using human embryonic stem cells and the difficulty of obtaining large numbers of adult stem cells (Belmonte et al., Nat Rev Genet, 2009). This approach is also not free from challenges like the mechanism of the reprogramming process, which has yet to be elucidated, and the warranties for safety of generated pluripotent cells, especially in view of their possible therapeutic use. Very recently, several new reprogramming methods have surfaced, which seem to be more appropriate than genetic reprogramming. Particularly, chemically induced pluripotent cells (CiPSs), obtained with recombinant proteins or small synthetic molecules, may represent a valid approach, simpler and possibly safer than the other ones.

[E-mail pediatric consultation]. / La consulenza pediatrica via e-mail.

Widespread diffusion of the Internet and of electronic mail allows contacting superspecialists all over the world, asking for information on health topics. We report our experience with e-mail consultation with the parents of the infants born at our hospital.

[Accreditation of hospital and local health unit management]. / L'accreditamento delle Direzioni Sanitarie di presidî ospedalieri e territoriali.

The authors state that an authoritative Clinical Director of a General Hospital, an active and efficient leadership of a Public Health District or Local Health Unit are very important to allow Italian Health Care System to cope with present and future challenges. The medical management must be professionally specialistic and be object of accreditation. This must be the target of professional training so that Medical Management Staff can have the necessary competence to carry complex management activities correctly out.

A case of complete adenylate kinase deficiency due to a nonsense mutation in AK-1 gene (Arg 107 --> Stop, CGA --> TGA) associated with chronic haemolytic anaemia.

Two siblings of Italian origin with mild chronic haemolytic anaemia, psychomotor impairment and undetectable adenylate kinase (AK) activity are reported. The other red cell enzyme activities were normal except for a slight decrease of PFK. 2,3-DPG levels were increased in both siblings, and AMP decreased in one only. The parents were not consanguineous and displayed intermediate AK activity. The sequence of complete erythrocyte AK-1 cDNA showed the presence of a nonsense homozygous mutation at codon 107 (CGA --> TGA, Arg --> Stop) in the siblings. The mutation results in a truncated protein of 107 amino acids in comparison with the 194 of the normal one. Moreover a 37 bp deletion in the first part of exon 6 (from nt 326 to nt 362 of the cDNA sequence) was detected in one allele; this deletion is not likely to further affect the enzyme structure, being localized after the stop codon. The new variant was named AK Fidenza, from the origin of the patients.

A variant of the EPB3 gene of the anti-Lepore type in hereditary spherocytosis.

The EPB3 gene encodes band 3 (anion exchanger 1) of the red cell membrane. A subset of hereditary spherocytosis (HS) is associated with EPB3 gene mutations and band 3 deficiency. We report a large Italian family in which 10 of the 27 members investigated displayed an autosomal dominant HS. SDS-PAGE revealed a reduction in band 3 in the patients. Screening of the Pst I polymorphic site confirmed the linkage of HS with the EPB3 gene. Analysis of complementary and genomic DNA showed a large additional segment. Nucleotide sequencing disclosed an in-frame duplication of 69 nucleotides (nt) including a triplet of intronic origin and a genuine exonic duplication of 66 nt. Two CCTGC sequences occurred close to one another, one near the intron 12 acceptor splice site (nt -7 to -3), and the other within exon 13 (nt 1494-1498). We assumed that the abnormal allele arose from an unequal recombination event of the anti-Lepore type between the two CCTGC sequences. At the level of the mutated protein, termed band 3 Milano, the additional segment (Gln plus duplication of residues 478-499) corresponded to the last part of the third transmembrane domain (TM3), the entire second outer loop and part of TM4 as it is currently defined in hydropathy analysis. After deglycosylation of band 3, only the normal band was detected, supporting the view that band 3 Milano is probably not incorporated into the membrane.

Molecular characterization of PK-LR gene in pyruvate kinase-deficient Italian patients.

We studied the PK-LR gene in 15 unrelated Italian patients with congenital hemolytic anemia associated with erythrocyte pyruvate kinase (PK) deficiency. Fourteen different mutations were detected among 26 mutated alleles identified: a five-nucleotide (nt) deletion (227 to 231), two splice-site (1269C and IVS3(-2)c), 10 missense (514C, 787T, 823A, 993A, 994A, 1168A, 1456T, 1529A, 1552A, and 1594T) and one nonsense mutation(s) (721T). Eight of these (deletion 227-231, 1269C, IVS3(-2)c, 514C, 787T, 823A, 1168A, and 1552A) were novel. Moreover, a new polymorphic site was detected in the 3' untranslated region of the mRNA (C/T, nucleotide 1738). The deletion 227-231 causes a stop codon after amino acid 77, probably resulting in an unstable gene product. Mutations 1269C and IVS3(-2)c lead to an alteration of the 5' and 3' splice-site consensus sequence, respectively; cDNA analysis failed to reveal any abnormal transcript, suggesting that these mutations generate an unstable mRNA that is rapidly degraded. Of the five new missense mutations, 823A (Gly275-Arg) and 1168A (Asp390-Asn) involve highly conserved amino acids, 514C (Glu172-Gln) and 1552A (Arg518-Ser), although found in less conserved regions, affect the balance of the electric charges of the protein. Mutation 787T (Gly263-Trp) is likely to determine strong modifications in the local structure of the molecule. The most frequent mutation in Italy appears to be 1456T (seven of 30 alleles), followed by 1529A (three of 30) and 994A (three of 30). A correlation was found between mutations, biochemical characteristics of the enzyme, and clinical course of the disease.

Seroprevalence of hepatitis B virus markers and risk factors in patients and staff of an Italian residential institution for the mentally disabled.

We conducted a cross-sectional study to evaluate the prevalence rate and risk factors for hepatitis B virus (HBV) infection among residents and staff at the Fatebenefratelli Institute in San Colombano in the province of Milan. We tested serum from 510 patients and 165 staff members. In addition, a medical record and a completed questionnaire were obtained from each patient. A total of 338 (66.5%) residents were found to have markers of HBV infection, including 29 (5.7%) who were identified as carriers. Thirty-nine members of staff (24.1%) showed evidence of HBV infection but only 1 (0.6%) was identified as a carrier. Among patients the prevalence rate of HBV was significantly associated with length of stay and age at admission, as it was with length of employment among staff members. The hepatitis B vaccine was offered to all patients and staff in the institution during 1994. A total of 143 (84%) patients and 111 (90%) members of the staff were vaccinated in the same year. To prevent the further spread of HBV infection in this institution, all current and future residents and staff members should be screened for serological markers for HBV and subjects identified as being susceptible should be vaccinated according to a compulsory routine policy.

Prevalence of HIV in normal and at risk population (seroepidemiological investigation during two years).

In this work we reported the results obtained using two ELISA-tests (the seropositivity was confirmed by Western-Blot) for detection of HIV-Ab in normal and at risk population (according by the classification from C.D.C. 1982) exposed to screening for various, sanitary measures. Our results concerning the percentage of seropositivity to HIV-Ab in drug-addicts (49%) are in agreement with the results obtained in the most qualified Italian Centres. The incidence of congenital infection is high, pointed 50%; the 100% of seropositive children were infected by drug-addicts seropositive parents. Casuistry among haemophilic patients we have demonstrated a greater seropositivity in B haemophilic subjects than A haemophilic ones. The seropositivity (24%) verified among prisoners is totally related to drug-addiction. Prevalence of seropositivity among heterosexual partners of HIV positive subjects was 22% among female partners of infected men, and 9% among male partners of infected women. Checking performed upon nursing staff who casually were contaminated by seropositive patient's blood confirmed 100% of seronegativity after eight months. No seropositive subjects were performed in every not a risk group.