The role of laboratory medicine in a value-based healthcare system: the example of heart failure patient management in the Italian context.

OBJECTIVE: As of today, healthcare systems worldwide face severe challenges that undermine their sustainability. The value-based healthcare (VBHC) approach has been proposed as a strategic and methodological framework to ensure the delivery of the best patient outcomes with economic efficiency. Through the illustrative example of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) for heart failure (HF) patient management in the context of the Italian National Healthcare system, this article explores the role that in vitro diagnostics (IVDs) can play in enabling value-based care models. SUBJECTS AND METHODS: 14 healthcare professionals representing the relevant professional figures involved in HF patient management met to revise the current HF patient journey and design a new care pathway that, leveraging on BNP/NT-proBNP, reflects the VBHC principles. RESULTS: The literature recognizes the dosage of BNP/NT-proBNP as the gold stan-dard for diagnosing HF. However, as of today, these IVDs are not employed at their full potential regarding HF patient management. A new patient journey is proposed so that patients are diagnosed early and properly monitored in the aftermath of hospitalization, improving outcomes at contained costs. CONCLUSIONS: As testified by the example of HF patient management in Italy, laboratory medicine can represent a lever for adopting value-based care models. Still, large-scale adoption of VBHC will call for structural reforms that revise how healthcare delivery is organized, measured, and reimbursed.

Prevalence of tick-borne encephalitis virus in Ixodes ricinus from a novel endemic area of North Eastern Italy.

In Alpine area of extreme North Eastern Italy the first autochthonous case of TBE was reported in 1998 and was followed by 45 cases during the period 2001-2007, thus defining this area as definitely endemic. An ecological survey evaluated the tick density and the Tick-borne encephalitis virus (TBEV) infection prevalence in tick collected in selected sites. In addition, TBE strains were characterized by sequencing and phylogenetic analysis. Overall, 2,361 ticks (2,198 nymphs and 163 adults) of the Ixodes ricinus L. species collected during 2005 and 2006 were examined. Five samples were positive for TBEV, corresponding to an overall prevalence rate of 0.21%. When analyzed by place, TBEV was discovered in three sites where the highest tick density was found. The difference of prevalence between high and low density areas tested to be statistically significant (P = 0.028). Phylogenetic analysis showed that four sequences clustered with the Neudoerfl prototype, while the other clustered with the Isosaari 17 strain and with a number of Slovenian isolates. In addition, a sequence detected in archival samples from one human case segregated with another variant, namely the Swedish Torö strain.

Neurological manifestation of tick-borne encephalitis in North-Eastern Italy.

Tick-borne encephalitis (TBE) is an infectious zoonotic disease, moving from Central Europe to other countries and still rare in Italy. The disease, produced by the European subtype virus, typically takes a biphasic course with neurological disorders of different severity during its second phase. We report the first three TBE cases in Friuli Venezia Giulia (FVG), characterised by extremely variable clinical features. Knowledge of these different presentations will assist physicians in increasing their level of attention to TBE also in this region, where no cases of TBE had been reported in the past, despite the fact that it borders countries with high prevalence of the infection.

Cognitive impairment and carotid atherosclerosis in a general Italian midlife and old population.

The authors describe the design and the general, ultrasonographic, neuropsychological methodology of an observational epidemiological population survey, named REMEMBER (Registry Evaluation Memory in Buttrio e Remanzacco) conducted in the northeast of Italy in a randomized stratified sample of 1,026 subjects (554 F and 472 M) aged 55-98 years. The study was planned as cross-sectional and longitudinal survey of cognitive impairment, cardiovascular risk factors, carotid atherosclerosis in a midlife and older Italian population sample. The objectives of the first phase are to assess the prevalence of the different types of dementia, the cognitive impairment non-dementia, the cardiovascular risk factors, the carotid intima-media thickness and arterial distensibility, and of depression. The conclusions of this study will make it possible to organize preventive and interventional strategies for these epidemic conditions.

Antigenic conservation of an immunodominant invariable region of the VlsE lipoprotein among European pathogenic genospecies of Borrelia burgdorferi SL.

Lyme disease is caused by genetically divergent spirochetes, including 3 pathogenic genospecies: Borrelia burgdorferi sensu stricto, B. garinii, and B. afzelii. Serodiagnosis is complicated by this genetic diversity. A synthetic peptide (C(6)), based on the 26-mer invariable region (IR(6)) of the variable surface antigen of B. burgdorferi (VlsE), was used as ELISA antigen, to test serum samples collected from mice experimentally infected with the 3 genospecies and from European patients with Lyme disease. Regardless of the infecting strains, mice produced a strong antibody response to C(6), which indicates that IR(6) is antigenically conserved among the pathogenic genospecies. Twenty of 23 patients with culture-confirmed erythema migrans had a detectable antibody response to C(6). A sensitivity of 95.2% was achieved, with serum samples collected from patients with well-defined acrodermatitis chronica atrophicans. Fourteen of 20 patients with symptoms of late Lyme disease also had a positive anti-IR(6) ELISA. Thus, it is possible that C(6) may be used to serodiagnose Lyme disease universally.

Evidence of Dbps (decorin binding proteins) among European strains of Borrelia burgdorferi sensu lato and in the immune response of LB patient sera.

Decorin binding proteins DbpA and DbpB act as Borrelia burgdorferi (B. burgdorferi) adhesins to decorin, and are able to elicit a persistent antibody response in the mouse; accordingly DbpA protein would seem to be promising in immunoprofilaxis of Lyme borreliosis (LB). This study examines the distribution of Dbp epitopes in European strains of B. burgdorferi, of different genospecies and the presence of antibodies to Dbps in human sera from patients suffering from early and late LB, as revealed by immunoblotting. Different levels of expression of Dbp epitopes were found both among and within genospecies; data from human sera indicate that Dbps are expressed during infection though not as strongly as in the mouse infection.

Role of the archistriatal nucleus taeniae in the sexual behavior of male Japanese quail (Coturnix japonica): a comparison of function with the medial nucleus of the amygdala in mammals.

Nucleus taeniae (Tn) is a prominent cell group within the medial archistriatum of birds. Based upon similarities in sex-steroid binding sites, this nucleus has been hypothesized to be homologous to the medial nucleus of the amygdala (Me) in mammals, which is known to modulate the expression of sexual behavior in rodents. We therefore tested whether or not Tn likewise plays a role in the expression of sexual behavior in male Japanese quail. We found that bilateral damage to Tn produced deficits in several components of male responses toward female stimuli that were indicative of decreased sexual arousal, including goal-oriented responses, vocalizations associated with courtship, and motor reflexes that precede copulation. Our results suggest that Tn influences a wide range of behavioral functions in response to sexual stimuli, and they indicate a function for this nucleus similar to that subserved by the Me in mammals. These results strengthen the argument that these sex-steroid accumulating cell groups are homologous and suggest a conservation of function for them despite the vastly divergent evolutionary histories separating birds and mammals.

Prenatal stress alters the size of the rostral anterior commissure in rats.

In rodents and other mammals, prenatal stress disrupts both sexual differentiation and sexual behavior. The present study examined the area of the anterior division of the anterior commissure (the Aca) in coronal, thionin-stained sections of prenatally stressed (P-S), and control male and female rats. Pregnant rats were exposed to thrice-daily heat, light, and restraint stress or left undisturbed during days 15-22 of pregnancy. Adult P-S and control males and females were killed, perfused, and their brains removed. Serial coronal sections (total of approximately 200 microm) through the rostral portion of the Aca (the rAca) were taken and stained with thionin. The sections were examined and traced under x25 using computerized microscopy to obtain the area in mm2. The data revealed that control females had a larger rAca compared to control males, and that P-S males had a larger rAca compared to control males; further, control males and P-S females were not significantly different, nor were control females and P-S males. These results suggest that, in rats, the Ac may be sexually dimorphic (in a direction similar to that described in humans) and that prenatal stress an event that modifies sex-typical behavior, physiology, and neuroanatomy reverses that sex difference.

Preoptic area infusions of morphine disrupt--and naloxone restores--parental-like behavior in juvenile rats.

As in the adult lactating female, opioids disrupt (and naloxone restores), parental behavior in juvenile rats (approximately 25 days of age). Because the preoptic area regulates the display of parental behavior in lactating females, we examined its parental behavior role in the juvenile rat. At 21 days of age, juvenile rats were implanted with bilateral cannulae aimed at the preoptic area using a modified Kopf stereotaxic and extrapolating from a developing-rat brain atlas [58], and divided into two groups: Initiation and maintenance. On day 25, the initiation group received bilateral infusions of either morphine (0.50 microgram), saline (0.25 microliter), or morphine plus naloxone (0.25 microgram). Thirty minutes later, they were exposed to three 1-6-day-old pups; the maintenance group was exposed to pups until they displayed 2 consecutive days of parental behavior, then infused. Morphine disrupted parental behavior in both the initiation and Maintenance groups, and naloxone restored the behavior to control/ saline levels. Parental behavior in the juvenile animal of both sexes, therefore, is under opioid regulation that parallels the adult female.

IgM and IgG significant reactivity to Borrelia burgdorferi sensu stricto, Borrelia garinii and Borrelia afzelii among Italian patients affected by Lyme arthritis or neuroborreliosis.

This survey evaluates the specificity of band patterns in immunoblot of sera taken from clinically defined cases of Lyme arthritis and neuroborreliosis, towards three locally isolated strains of Borrelia burgdorferi, belonging to the three species: Borrelia sensu stricto, Borrelia garinii and Borrelia afzelii. To assess specificity, patient sera were statistically (X2, P < or = 0.05) compared with blood donors sera samples. Both IgG and IgM antibodies were considered. The overall reactivity of the three Borrelia strains in IgG immunoblots indicated that ten protein bands were significant, with a different prevalence of some of them in the two groups of patient sera: bands at 60-58, 30-33, 36-37 and 28-27 kDa were markers for neuroborreliosis sera; proteins at 100-83, 72-70 and 18-17 kDa behaved like markers for Lyme arthritis. The IgM Immunoblots revealed significant bands at 100-83, 72-70, 51, 24-21 and 18-17 kDa only with neuroborreliosis sera. Though there were variable band reactivities in each strain, a correlation emerged between the three genospecies and the clinical symptoms: in fact B. afzelii and B. garinii were prevalent in Lyme arthritis sera, (IgG Immunoblots); B. garinii was associated to neuroborreliosis (IgG and IgM Immunoblots); B. sensu stricto was strongly reactive with neuroborreliosis in IgM immunoblots. These data indicate that the three locally strains of Borrelia representing the three genospecies should be used together in immunoblot to detect antibodies elicited in neuroborreliosis and Lyme arthritis.