Drug utilization, safety, and effectiveness of exenatide, sitagliptin, and vildagliptin for type 2 diabetes in the real world: data from the Italian AIFA Anti-diabetics Monitoring Registry.

BACKGROUND AND AIMS: In Italy, the reimbursed use of incretin mimetics and incretin enhancers was subject to enrollment of patients into a web-based system recording the general demographic and clinical data of patients. We report the utilization data of glucagon-like peptide 1 (GLP1) receptor agonists and dipeptidylpeptidase-4 (DPP4) inhibitors in clinical practice as recorded by the Italian Medicines Agency (AIFA) Monitoring Registry. METHODS AND RESULTS: From February 2008 to August 2010, 75,283 patients with type 2 diabetes were entered into the registry and treated with exenatide, sitagliptin, or vildagliptin. The treatment was administered to patients in a wide range of ages (≥75 years, n = 6125 cases), body mass index (BMI) (≥35 kg/m(2), n = 22,015), and metabolic control (HbA(1c) ≥ 11% ((96 mmol/mol), n = 3151). Overall, 1116 suspected adverse drug reactions were registered, including 12 cases of acute pancreatitis (six on exenatide). Hypoglycemic episodes mainly occurred in combination with sulfonylureas. Treatment discontinuation for the three drugs (logistic regression analysis) was negatively associated with the male gender and positively with baseline HbA1c, diabetes duration, and, limitedly to DPP-4 inhibitors, with BMI. Treatment discontinuation (including loss to follow-up, accounting for 21-26%) was frequent. Discontinuation for treatment failure occurred in 7.7% of cases (exenatide), 3.8% (sitagliptin), and 4.1% (vildagliptin), respectively, corresponding to 27-40% of all discontinuations, after excluding lost to follow-up. HbA1c decreased on average by 0.9-1.0% (9 mmol/mol). Body weight decreased by 3.5% with exenatide and by 1.0-1.5% with DPP-4 inhibitors. CONCLUSIONS: In the real world of Italian diabetes centers, prescriptions of incretins have been made in many cases outside the regulatory limits. Nevertheless, when appropriately utilized, incretins may grant results at least in line with pivotal trials.

[The use of procedures volume indicators in an Italian Teaching Hospital]. / L'utilizzo degli indicatori di volume legati alle prestazioni. Esperienza di un Policlinico Universitario.

In a context of continuous spread health technologies, in which particular intensive procedures are performed, the use of procedure volume indicators supports the decision making process in monitoring and improving the healthcare quality. The aim of our work focuses on the evaluation of the association between the volume of procedures performed by organizational units inside an Italian University Hospital and the results in terms of mortality and prolonged length of stay (LOS). Volume indicators concerning esophageal resection, pancreatic resection, abdominal aortic aneurysm repair, coronary artery bypass graft and percutaneous transluminal coronary angioplasty were analysed according to the Agency of Health Care Research and Quality's criteria. A retrospective observational study was conducted analysing hospital discharged databases and operating room records for the period 2000-2005. Descriptive and inferential statistical analysis were performed using SPSS software 13.0 version. Regarding prolonged LOS, a statistical significant difference emerged among high and low volume organizational units for pancreatic resections, bypass, and angioplasty with respectively adjusted OR at 2.4 (C.I. 95% 1.04-5.53); 1.67 (C.I. 95% 1.29-2.16) and 3.34 (CI 95% 2.60-4.28). For mortality, a statistical significant difference emerged for abdominal aortic aneurysm repair and bypass with respectively OR at 21.02 (C.I. 95% 2.22-199.64) and 26.55 (C.I. 95% 15.30 - 46.07). The use of procedure volume indicators could help hospital administrators and medical professionals balance competing values such as control of cost and continuous quality improvement.

Preliminary investigation of extracellular vesicles in mammary cancer of dogs and cats: Identification and characterization.

Extracellular vesicles (EVs) are membrane-bound vesicles produced by cells, known to play a key role in cell-to-cell communication. They exert pleiotropic biological functions via the horizontal transfer of bioactive molecules (DNA, RNAs, proteins, and lipids) within the tumour microenvironment and throughout the body. In human cancer, EVs are known to interfere with pathways that lead to tumour progression and are used as novel cancer biomarkers. In veterinary medicine, very little is known on cancer-derived EVs. In this study, we preliminarily characterized EVs in mammary gland cancer of dogs and cats. EVs were isolated by ultracentrifugation from canine (CYPp), feline (FMCp) and human (MCF7) mammary tumour cell lines. EVs were visualized by transmission electron microscopy (TEM), counted using nanoparticle tracking analysis (NTA) and characterized by immunogold (CD63 and Alix) and western blot (Alix and TSG101). Additionally, EV production by "donor" cells (palmtdTomato+ ) and uptake by "recipient" cells (GFP+ ) were assessed. EVs were successfully isolated from all 3 cell lines by ultracentrifugation. Membrane-bound structures (50-400 nm) were identified by TEM and were positive for both CD63 and Alix at immunogold. Western blot showed positivity of EVs to Alix and TSG101. NTA analysis detected EVs from cell culture media ranging from 1.67 to 2.56 × 102 as number of EVs/cell and from 80 to 600 nm in size. Confocal microscopy identified the presence of palmtdTomato+ EVs into the cytoplasm of GFP+ cells. This preliminary study identified and characterized canine and feline mammary tumour cell-derived EVs, opening in veterinary medicine a new interesting unexplored field with several applications and limitless potential.

Pricing and reimbursement experiences and insights in the European Union and the United States: Lessons learned to approach adaptive payer pathways.

Earlier patient access to beneficial therapeutics that addresses unmet need is one of the main requirements of innovation in global healthcare systems already burdened by unsustainable budgets. "Adaptive pathways" encompass earlier cross-stakeholder engagement, regulatory tools, and iterative evidence generation through the life cycle of the medicinal product. A key enabler of earlier patient access is through more flexible and adaptive payer approaches to pricing and reimbursement that reflect the emerging evidence generated.

A preliminary investigation of the role of the transcription co-activators YAP/TAZ of the Hippo signalling pathway in canine and feline mammary tumours.

Breast cancer is the most common cancer in women worldwide. Cancer metastases are responsible for the high mortality rate. A small but distinct subset of cells, cancer stem cells (CSCs), have the capacity to self-renew, initiate tumour formation, and develop metastases. The CSC content in human breast cancer correlates with the Hippo tumour suppressor signalling pathway. Specifically, the activity of YAP/TAZ, transcription co-activators of the Hippo pathway, sustains the self-renewal and tumour-initiation capacities of CSCs. Little is known about YAP/TAZ in canine and feline mammary tumours, which are very common tumours. The preliminary aim of the study was to investigate the expression of YAP/TAZ in canine and feline mammary tumours by Western blot and immunohistochemistry. Increased cytoplasmic and nuclear expression of YAP/TAZ was observed in all carcinomas compared to normal tissues, indicating neoplastic deregulation of the Hippo pathway. Nuclear expression significantly increased in grade III (high grade carcinomas) compared to grade I (low grade carcinomas) tumours, suggesting that YAP/TAZ play a role in the increased aggressiveness of these tumours. Moreover, different scoring systems for immunohistochemical analyses were compared and the H index and the Allred scores were the most significant. In conclusion, YAP/TAZ are expressed in aggressive canine and feline mammary tumours as reported in some human cancers. Further studies might better elucidate the role of the Hippo pathway in prognosis and as a target for new therapies. In addition, tumours in dogs and cats may be a useful model to study this pathway.

Psychosocial stages and quality of life of women with breast cancer.

Certain issues are universal for all women with breast cancer, irrespective of age, ethnic group, or stage of disease. Yet, along with common concerns, experiences, and anxieties, each woman may encounter a unique set of problems. Ultimately, each woman's adaptation and choices will be strongly influenced by her personal history, her psychosocial stage, and her life-cycle concerns. Changes in the criteria norms for the psychosocial stages of women's lives and their subsequent influence on quality of life are issues that have substantial implications for nursing and other healthcare professions. Younger and older women have different needs, concerns, and quality of life issues in a context of psychosocial life stages that have changed significantly across the post-World War II generations. The experience of breast cancer is perceived differently by women of distinct psychosocial life stages. At each critical life stage, the unique emerging problems require specific psychosocial supports that can reduce or avert the ensuing emotional distress. The planning and implementation of care must be tailored to address the differences demonstrated by age and psychosocial life stage, and to enhance quality of life outcomes for survivors of breast cancer, both young and old.

Perceived social support, uncertainty, and quality of life of younger breast cancer survivors.

This study investigated the relationship between perceived social support, uncertainty, and quality of life among younger breast cancer survivors. Proposed hypotheses predicted a significant positive correlation between perceived social support and quality of life, a significant negative correlation between uncertainty and quality of life, and that perceived social support and uncertainty, considered together, will explain more of the variance of quality of life than either variable considered independently. A sample of 101 breast cancer survivors below age 50 completed the Social Support Questionnaire, Mishel Uncertainty in Illness Scale--Community Form, and Ferrans and Powers Quality of Life Index--Cancer Version. Data were analyzed using Pearson product-moment correlation and stepwise multiple regression. All three hypotheses were supported. Additional findings revealed a significant positive correlation between support and network size, and between network size and the socioeconomic domain of quality of life. Significant negative correlations were found between perceived social support and uncertainty, between network size and time since diagnosis and treatment, and between network size and uncertainty. Study results demonstrated that although perceived social support and uncertainty accounted for a significant amount (27.2%) of variance of quality of life, a large amount of variance remains unexplained. Further research is needed in this area.