Effectiveness of clinical pathway in subjects with heart failure: A real-world study from Italian health claims

Background: Several process-of-care indicators have been developed and implemented to improve the quality of heart failure (HF) patients care. The aim of this study is to assess the relationship between a set of recommendations for HF care with measurable clinical outcomes, also in terms of outcomes that could be avoided. Methods: A retrospective cohort study was carried out on subjects with at least one hospitalization with a primary diagnosis of HF in 2007. Data were retrieved from healthcare utilization databases of Lombardy region (Italy). Exposure to selected recommendations (periodic control of echocardiogram and use of blockers of the renin-angiotensin system and beta-blockers) was recorded. All cause mortality and hospitalization with primary diagnosis of HF were considered as outcomes. Multivariable Cox models and Poisson model were fitted to estimate the exposure-outcome association. Results: Among 8207 cases of HF, those who adhered to none, one or all recommendations during the first year after diagnosis were 11%, 60% and 30%, respectively. Compared to patients who adhered to no recommendation, a significant mortality risk reduction of 24% (95% CI 17-31%) and 44% (36 52%) were observed for those who adhered to one and all recommendations, respectively. A significant reduction in the rate of re-hospitalizations in subjects adhered to at least one recommendation was also observed. A decreased trend in Population Attributable Fraction for death cases according to follow-up time was observed. Conclusion: A strict control of patients with HF through regular clinical examinations must be considered as fundamental for the reduction of mortality and re-hospitalizations

Confronto tra Inquiry-based Science Education ed insegnamento tradizionale delle Scienze in alcune scuole superiori italiane

This study aims to evaluate if inquiry-based science education (IBSE) at the high school level allows the achievement of better learning objectives with respect to conventional science education (CSE). The findings would help to understand if, how, and why IBSE can be used as a successful teaching approach. The study included four high schools with different specialties, eight experienced science teachers and approximately 350 students, attending sixteen classes. Two biochemistry topics were taught by the same teacher in two classes. A two stage quasi experimental, crossover design was adopted. The primary outcome compared the difference in the average pre-teaching and post-teaching test-scores, using a 3-multilevel analysis. On average, the outcome in terms of scores significantly improved by 4% with IBSE with respect to the CSE approach, demonstrating differences among the school specialties. In conclusion, our study indicates that IBSE is significantly more effective in enhancing skills.Questo studio mira a valutare se l’approccio “Inquiry-based science education” (IBSE) consenta il raggiungimento di obiettivi di apprendimento, a livello di scuola superiore, in modo più efficacerispetto all’educazione scientifica convenzionale (CSE). I risultati possono aiutare a capire se, come e perché IBSE può essere utilizzato come approccio didattico di successo. Lo studio ha inclusoquattro scuole superiori con diversi indirizzi, otto insegnanti di scienze con esperienza e circa 350 studenti, suddivisi in sedici classi. Due tematiche di biochimica sono state insegnate dallo stesso docente in due classi parallele. È stato adottato un disegno quasi sperimentale, crossover, a due fasi. Obiettivo primario è stato confrontare la differenza nei punteggi medi nei test prima e dopo le attività, utilizzando un’analisi gerarchica a 3 livelli. In media, il risultato in termini di punteggi è migliorato significativamente del 4% con IBSE rispetto all’approccio CSE, dimostrando differenze tra gli indirizzi scolastici. In conclusione, il nostro studio indica che IBSE è significativamente più efficace nel migliorare le competenze

Ex-vivo recruitment and x-ray assessment of donor lungs in a challenging retrieval from a donor supported by lvad using the portable normothermic perfusion system: A case report

Lung transplantation (LTx) is limited by the shortage of suitable donors. To overcome this problem, many programs have begun to use donors with extended criteria (marginal donors). However, brain-dead patients with implanted mechanical circulatory support system have rarely been considered as potential lung donors. This case demonstrates the feasibility of lung transplantations from organ donors supported by a mechanical circulatory support system despite the possible difficulties of lung retrieval. CASE PRESENTATION: Our case presents a successful procurement and bilateral lung transplantation from a donor supported by a left ventricular assist device (LVAD) who experienced an intraoperatively haemodynamic complication. The use of portable normothermic perfusion device let us to reduce ischemic injury and assess these marginal donor lungs helping us to determine the clinical suitability for transplantation. Given our extensive experience with the device instrumentation and management, the EVLP process was uneventful with excellent post-transplant course. CONCLUSIONS: This case report demonstrates the feasibility of lung transplantations from organ donors supported by a mechanical circulatory support system using the portable normothermic perfusion platform to assess and preserve these donor lungs

Real-world assessment of healthcare provided by the National Health Service: The network of regional Beaver research platforms

Real-world evidence can provide answers on healthcare utilization and appropriateness, post-marketing drugs safety and comparative effectiveness, and cost-effectiveness profiles of healthcare pathways. Healthcare utilization databases, possibly integrated with drug and disease registries, electronic medical records, survey and cohort data (i.e. real-world data), allow to trace healthcare ‘footprints’ left from beneficiaries of National Health Service. Beaver is a research platform available on demand to Italian regions which we developed for computing indicators of healthcare utilization and clinical outcomes, as well as for generating evidence on effectiveness and cost-effectiveness profile. Two distinct solutions may be adopted. One, the so-called Beaver Light front-end allows to automatically compute health indicators of adherence to official guidelines. Two, the so-called Beaver Full front-end involves an eight-step procedure entirely driven by the study protocol. In order to fulfil the directives recently issued by the European Parliament and Council and the Italian Authority for the protection of individual data, the platform resides in each region’s infrastructure, so limiting the free movement of electronic health data. Indeed, regional authorities should be responsible for data safety and for allowing data accessibility. The use of standardized and validated algorithms enables to obtain regional estimates that, being obtained by employing regional platforms containing data extracted with standardized procedure, may be compared and possibly summarized by using common meta-analytic techniques. In conclusion, the Beaver regional platform is a promising tool which may contribute to stimulate healthcare research in Italy

Marked alveolar apoptosis/proliferation imbalance in end-stage emphysema.

BACKGROUND: Apoptosis has recently been proposed to contribute to the pathogenesis of emphysema. METHODS: In order to establish if cell fate plays a role even in end-stage disease we studied 16 lungs (9 smoking-associated and 7 alpha1antitrypsin (AAT)-deficiency emphysema) from patients who had undergone lung transplantations. Six unused donor lungs served as controls. Apoptosis was evaluated by TUNEL analysis, single-stranded DNA laddering, electron microscopy and cell proliferation by an immunohistochemical method (MIB1). The role of the transforming growth factor (TGF)-beta1 pathway was also investigated and correlated with epithelial cell turnover and with the severity of inflammatory cell infiltrate. RESULTS: The apoptotic index (AI) was significantly higher in emphysematous lungs compared to the control group (p < or = 0.01), particularly if only lungs with AAT-deficiency emphysema were considered (p < or = 0.01 vs p = 0.09). The proliferation index was similar in patients and controls (1.9 +/- 2.2 vs 1.7 +/- 1.1). An increased number of T lymphocytes was observed in AAT-deficiency lungs than smoking-related cases (p < or = 0.05). TGF-beta1 expression in the alveolar wall was higher in patients with smoking-associated emphysema than in cases with AAT-deficiency emphysema (p < or = 0.05). A positive correlation between TGF-betaRII and AI was observed only in the control group (p < or = 0.005, r2 = 0.8). A negative correlation was found between the TGF-beta pathway (particularly TGF-betaRII) and T lymphocytes infiltrate in smoking-related cases (p < or = 0.05, r2 = 0.99) CONCLUSION: Our findings suggest that apoptosis of alveolar epithelial cells plays an important role even in end-stage emphysema particularly in AAT-deficiency disease. The TGFbeta-1 pathway does not seem to directly influence epithelial turnover in end-stage disease. Inflammatory cytokine different from TGF-beta1 may differently orchestrate cell fate in AAT and smoking-related emphysema types

EGF and IGF1 affect Sunitinib activity in BP-NEN: new putative targets beyond VEGFR?

Broncho-Pulmonary Neuroendocrine Neoplasms (BP-NENs) are neoplasms orphan of an efficient therapy. Available medical treatments derived from clinical trials are not specific for the management of this malignancy. Sunitinib is a multi-receptor tyrosine-kinases (RTKs) inhibitor that has already shown its efficacy in NENs but there are not available data about its action in BP-NENs. Therefore, our aim was to understand the effects of RTKs inhibition promoted by Sunitinib in order to evaluate new putative targets useful in malignancy treatment. Since our results underlined a role for EGFR and IGF1R in modulating Sunitinib antiproliferative action, we investigated the effects of Erlotinib, an EGFR inhibitor, and Linsitinib, an IGF1R inhibitor, in order to understand their function in regulating cells behaviour. Cell viability and caspase activation were evaluated on two immortalized human BP-NEN cell lines and primary cultures. Our results showed that after treatment with Sunitinib and/or IGF1, EGF and VEGF, the antiproliferative effect of Sunitinib was counteracted by EGF and IGF1 but not by VEGF. Therefore, we evaluated with alpha-screen technology the phosphorylated EGFR and IGF1R levels in primary cultures treated with Sunitinib and/or EGF and IGF1. Results showed a decrease of p-IGF1R after treatment with Sunitinib and an increase after co-treatment with IGF1. Then, we assessed cell viability and caspase activation on BP-NEN cell lines after treatment with Linsitinib and/or Erlotinib. Results demonstrate that these two agents have a stronger antiproliferative effect compared to Sunitinib. In conclusion, our results suggest that IGF1R and EGF1R could represent putative molecular targets in BP-NENs treatment

Detection of circulating immunosuppressive cytokines in malignant pleural mesothelioma patients for prognostic stratification.

Abstract Background No data on circulating biomarkers for the prognostic stratification of Malignant Pleural Mesothelioma (MPM) patients are available. We prospectively explored the prognostic role of circulating monocyte and cytokine levels and their dynamic change during chemotherapy. Patients and Methods MPM patients receiving a first line treatment based on a platinum compound plus pemetrexed were eligible. Blood samples were collected at the baseline and at the end of induction chemotherapy. CCL-2, IL-10 and TGF-β levels in plasma were quantified by Enzyme-Linked Immunosorbent Assay (ELISA); white blood cells, monocytes and platelets were evaluated by blood count test. Results Thirty-one patients were included in the study. Median overall survival (OS) was 12.13 months versus 9.6 months in patients with lower and higher monocytes count, respectively (p value = 0.02). We further stratified patients according to a combined score based on the association of IL-10, TGF-β levels and monocytes count. High combined score was associated with shorter OS and PFS in univariate and multivariate analysis. Chemotherapy induced an increase in monocytes, IL-10, but not TGF-β levels. Conclusion The prognostic value of circulating levels of multiple immunosuppressive cytokines and inflammatory cells should be confirmed in a wider validation set of MPM patients