Can italian healthcare administrative databases be used to compare regions with respect to compliance with standards of care for chronic diseases?

BACKGROUND: Italy has a population of 60 million and a universal coverage single-payer healthcare system, which mandates collection of healthcare administrative data in a uniform fashion throughout the country. On the other hand, organization of the health system takes place at the regional level, and local initiatives generate natural experiments. This is happening in particular in primary care, due to the need to face the growing burden of chronic diseases. Health services research can compare and evaluate local initiatives on the basis of the common healthcare administrative data.However reliability of such data in this context needs to be assessed, especially when comparing different regions of the country. In this paper we investigated the validity of healthcare administrative databases to compute indicators of compliance with standards of care for diabetes, ischaemic heart disease (IHD) and heart failure (HF). METHODS: We compared indicators estimated from healthcare administrative data collected by Local Health Authorities in five Italian regions with corresponding estimates from clinical data collected by General Practitioners (GPs). Four indicators of diagnostic follow-up (two for diabetes, one for IHD and one for HF) and four indicators of appropriate therapy (two each for IHD and HF) were considered. RESULTS: Agreement between the two data sources was very good, except for indicators of laboratory diagnostic follow-up in one region and for the indicator of bioimaging diagnostic follow-up in all regions, where measurement with administrative data underestimated quality. CONCLUSION: According to evidence presented in this study, estimating compliance with standards of care for diabetes, ischaemic heart disease and heart failure from healthcare databases is likely to produce reliable results, even though completeness of data on diagnostic procedures should be assessed first. Performing studies comparing regions using such indicators as outcomes is a promising development with potential to improve quality governance in the Italian healthcare system

Evolution and clinical impact of co-occurring genetic alterations in advanced-stage EGFR-mutant lung cancers

A widespread approach to modern cancer therapy is to identify a single oncogenic driver gene and target its mutant-protein product (for example, EGFR-inhibitor treatment in EGFR-mutant lung cancers). However, genetically driven resistance to targeted therapy limits patient survival. Through genomic analysis of 1,122 EGFR-mutant lung cancer cell-free DNA samples and whole-exome analysis of seven longitudinally collected tumor samples from a patient with EGFR-mutant lung cancer, we identified critical co-occurring oncogenic events present in most advanced-stage EGFR-mutant lung cancers. We defined new pathways limiting EGFR-inhibitor response, including WNT/β-catenin alterations and cell-cycle-gene (CDK4 and CDK6) mutations. Tumor genomic complexity increases with EGFR-inhibitor treatment, and co-occurring alterations in CTNNB1 and PIK3CA exhibit nonredundant functions that cooperatively promote tumor metastasis or limit EGFR-inhibitor response. This study calls for revisiting the prevailing single-gene driver-oncogene view and links clinical outcomes to co-occurring genetic alterations in patients with advanced-stage EGFR-mutant lung cancer

Fungal vincristine from Eutypella spp-CrP14 isolated from Catharanthus roseus induces apoptosis in human squamous carcinoma cell line-A431

Background: Catharanthus roseus, a medicinal plant, is known to produce secondary metabolites, vincristine and vinblastine, which are terpenoid indole alkaloids. Previously we have reported that Eutypella spp - CrP14 isolated from stem cutting of this plant had shown significant antiproliferative activity when tested in vitro against HeLa cell line. The present study was conducted to identify the anticancer compound responsible for the anti-proliferative activity of the fungal extract and to evaluate its in vitro anticancer and apoptotic effects. Methods: The anti-proliferative activity of the fungal anticancer compound, vincristine was analyzed by MTT assay against different cancer cell lines. We examined its efficacy of apoptotic induction on A431 cells. The parameters examined included cell cycle distribution, loss of mitochondrial membrane potential (MMP), DNA fragmentation and reactive oxygen species (ROS) generation. Results: The presence of vincristine in fungal culture filtrate was confirmed through chromatographic and spectroscopic analyses, and the amount was estimated to be 53 +/- 5.0 mu g/l. The partially purified fungal vincristine had strong cytotoxic activity towards human squamous carcinoma cells - A431 in the MTT assay. Furthermore, we showed that the fungal vincristine was capable of inducing apoptosis in A431 cells through generation of reactive oxygen species and activation of the intrinsic pathway leading to loss of MMP. Conclusions: We have demonstrated for the first time that the vincristine from Eutypella spp - CrP14 is an efficient inducer of apoptosis in A431 cells, meriting its further evaluation in vivo

Classification trees for ordinal variables

CART, Gini–Simpson criterion, Gini index of heterogeneity, Ordered categorical variables, Twoing criterion,