Treatment of osteolytic solitary painful osseous metastases with radiofrequency ablation or cryoablation: a retrospective study by propensity analysis

The present study aimed to measure the improvement in pain relief and quality of life in patients with osteolytic solitary painful bone metastasis treated by cryoablation (CA) or radiofrequency ablation (RFA). Fifty patients with solitary osteolytic painful bone metastases were retrospectively studied and selected by propensity analysis. Twenty-five patients underwent CA and the remaining twenty-five underwent RFA. Pain relief, in terms of complete response (CR), the number of patients requiring analgesia and the changes in self-rated quality of life (QoL) were measured following the two treatments. Thirty-two percent of patients treated by CA experienced a CR at 12 weeks versus 20% of patients treated by RFA. The rate of CR increased significantly with respect to baseline only in the group treated by CA. In both groups there was a significant change in the partial response with respect to baseline (36% in the CA group vs. 44% in the RFA group). The recurrence rate in the CA and RFA groups was 12% and 8%, respectively. The reduction in narcotic medication requirements with respect to baseline was only significant in the group treated by CA. A significant improvement in self-rated QoL was observed in both groups. The present study seems to suggest that CA only significantly improves the rate of CR and decreases the requirement of narcotic medications. Both CA and RFA led to an improvement in the self-rated QoL of patients after the treatments. However, the results of the present study should be considered as preliminary and to serve as a framework around which future trials may be designed

Cost‑effectiveness analysis of apixaban versus other NOACs for the prevention of stroke in Italian atrial fibrillation patients

OBJECTIVES: The study evaluated the cost‑effectiveness of apixaban in preventing thromboembolic events in non‑valvular atrial fibrillation (NVAF) patients, as compared to other three available novel oral anticoagulant agents (NOACs), from the Italian Health System (SSN) perspective.METHODS: A previously published lifetime Markov model was adapted for the Italian context. Baseline clinical risks were assigned based on the demographic and clinical features of the patients; effectiveness and safety parameters derived from adjusted indirect comparison using warfarin as link. The main clinical events considered in the model are ischemic and hemorrhagic stroke, systemic thromboembolism, bleeds (both major and clinically relevant minor) and cardiovascular hospitalizations, besides treatment discontinuations. Expected survival was projected beyond trial duration using national mortality data adjusted for clinical risks and weighted by published utilities. Unit costs were collected from published Italian sources and actualized to 2013. Costs and health gains occurring after the first year were discounted at an annual 3.5% rate. The primary outcome measure of the economic evaluation was the incremental cost effectiveness ratio (ICER), where effectiveness is measured in terms of life‑years and quality adjusted life‑years gained. Deterministic and probabilistic sensitivity analyses (DSA&PSA) were carried out.RESULTS: In the short to medium term, apixaban was associated with marginal LYs and QALYs gains and slight savings, as compared to other NOACs. However, as apixaban extended expected survival versus dabigatran (110mg), dabigatran (150mg) and rivaroxaban (0.13, 0.08, and 0.06 LYs or 0.11, 0.07, and 0.05 QALYs), expected total lifetime costs exceeded those of these comparators (€ 319, € 282, and € 16). Corresponding ICERs were estimated in € 2,911, € 3,882 and € 327 per QALY gained. The most influential parameter according to DSA was daily costs of NOACs, but the corresponding ICERs remained well below commonly accepted WTP values. In PSA, the probabilities of apixaban being cost effective with a WTP threshold of 20,000 €/QALY gained were 99%, 92% and 93% for the same comparisons.CONCLUSIONS: Apixaban is expected to be more effective than dabigatran and rivaroxaban in Italian NVAF population, and marginally more costly due to consume healthcare resources for a longer period of time. The ICERs have a high likelihood of being below conventional thresholds of WTP for health benefits of the SSN and suggest that apixaban is cost‑effective compared with other three available NOACs

Budget impact analysis of apixaban versus other NOACs for the prevention of stroke in Italian atrial fibrillation patients

OBJECTIVE: This study aims to perform a budget impact analysis of the use of three available novel oral anticoagulant agents (NOACs) for preventing thromboembolic events in Italian patients with non‑valvular atrial fibrillation (NVAF).METHODS: Estimated Italian population of patients was run through a previously published lifetime decision tree/Markov model simulating their treatment with the available therapeutic options: dabigatran at two dose levels (110 mg/bid for the over 80 years old, 150 mg/bid for younger NVAF patients), rivaroxaban (20 mg/uid), and apixaban (5 mg/bid). Effectiveness and safety estimates derive from an adjusted indirect treatment comparison using warfarin as link. The main clinical events considered in the model are ischemic and hemorrhagic stroke, systemic thromboembolism, bleeds (both major and clinically relevant minor) and cardiovascular hospitalizations, besides treatment discontinuations. Epidemiological data and unit costs, actualized to 2013, are collected from Italian published sources. The budget impact analysis evaluates the financial impact of apixaban introduction by comparing expected 1,2, and 3 years costs in hypothetical scenarios: with and without apixaban. Italian NVAF patient population estimation is based on official apixaban reimbursement criteria, applying the characteristics of the trial population to national epidemiologic data. Numbers of patients for each regimen are estimated by projecting share evolution. Sensitivity analysis is performed on an alternative non‑experimental population of NVAF patients.RESULTS: Among available NOACs, apixaban was expected to be the least expensive in an estimated patient population of 364,000 Italian patients, allowing for savings of € 1,180,549, € 3,841,429 and € 5,368,918 at 1,2, and 3 years, respectively. Results of the simulation run on an alternative non‑experimental population of NVAF patients yields comparable estimates.CONCLUSIONS: The different safety and effectiveness profiles of the three available NOACs emerging from the adjusted indirect comparison indicate that apixaban could improve health care expenditure control while maintaining or increasing therapeutic appropriateness in the Italian NVAF population

Crystallization driven boost in fill factor and stability in additive-free organic solar cells

The control of morphology and microstructure during and after the active layer processing of bulk-heterojunction solar cells is critical to obtain elevated fill factors and overall good device performance. With the recent development of non-fullerene acceptors, wide attention has been paid to improve miscibility, solubility and nanoscale separation by laborious molecular design processes and by the use of additives. Nonetheless, several post-processing strategies can equally contribute to obtain an optimum phase separation and even to an enhanced crystallinity, but their effect on performance and device lifetime of polymer/non-fullerene acceptor solar cells is still unclear. Herein, we report a systematic comparison between different post-processing treatments including thermal annealing (TA), vacuum drying (VD) and solvent vapor annealing (SVA) on the TPD-3F polymer and IT-4F non-fullerene acceptor, comparing their effects on device performance as well as on the morphology and optical and electrical properties. The optimized SVA treated devices exhibited power conversion efficiencies close to 14% with a remarkable 76% fill factor and superior short-circuit currents compared to the one of untreated devices. Moreover, SVA demonstrated improvements in device stability both under illumination and under ambient conditions. The induced phase separation and the increased crystallinity of the acceptor molecules, as revealed by GIWAXS measurements, led to increased photogenerated currents, with a more effective exciton dissociation and charge collection. The open-circuit voltage losses in the SVA and TA devices were explained by a bandgap reduction and a higher trap-assisted recombination, respectively. Overall, our study points to the role of post-processing in organic solar cell fabrication, and contributes towards a new generation of efficient and stable additive-free organic solar cells

Comparative pharmacoeconomic assessment of apixaban vs. standard of care for the prevention of stroke in Italian atrial fibrillation patients

OBJECTIVES: The aim of this study was to evaluate the cost‑effectiveness of apixaban in the prevention of thromboembolic events in patients with non‑valvular atrial fibrillation (NVAF) relatively to standard of care (warfarin or aspirin) from the Italian National Health System (SSN) perspective.METHODS: A previously published lifetime Markov model was adapted for Italian context. Clinical effectiveness data were acquired from head‑to‑head randomized trials (ARISTOTLE and AVERROES); main events considered in the model were ischemic and hemorrhagic stroke, systemic thromboembolism, bleeds (both major and clinically relevant minor) and cardiovascular hospitalizations, besides treatment discontinuations. Expected survival was projected beyond trial duration using national mortality data adjusted for individual clinical risks and adjusted by utility weights for health states acquired from literature. Unit costs were collected from published Italian sources and actualized to 2013. Costs and health gains accruing after the first year were discounted at an annual 3.5% rate. The primary outcome measure of the economic evaluation was the incremental cost effectiveness ratio (ICER), where effectiveness is measured in terms of life‑years and quality adjusted life‑years gained. Deterministic and probabilistic sensitivity analyses (PSA) were carried out to assess the effect of input uncertainty.RESULTS: Apixaban is expected to reduce the incidence of ischemic events relative to aspirin and to improve bleeding safety profile when compared to warfarin. Incremental LYs (0.31/0.19), QALYs (0.28/0.20), and costs (1,932/1,104) are predicted with the use of apixaban relative to aspirin and warfarin, respectively. The ICERs of apixaban were € 6,794 and € 5,607 per QALY gained, respectively. In PSA, the probability of apixaban being cost effective relative to aspirin and warfarin was 95% and 93%, respectively, for a WTP threshold of € 20,000 per QALY gained. Univariate analyses indicate that results were most sensitive to variations of the absolute risk reduction for cardiovascular events with apixaban.CONCLUSIONS: Apixaban is expected to increase life expectancy and quality‑adjusted life expectancy, but also costs dedicated to Italian NVAF patients, as compared to standard of care. The resulting ICERs have high probabilities of being below the conventional thresholds of WTP for health benefits of the SSN, indicating efficient allocation of health care resources

Treatment of Solitary Painful Osseous Metastases with Radiotherapy, Cryoablation or Combined Therapy: Propensity Matching Analysis in 175 Patients

aim of this study was to identify outcomes in pain relief and quality of life in patients with a solitary painful osseous metastasis treated by radiotherapy, cryoablation or the combination using a propensity score matching study design

Circulating tumour cells in colorectal cancer

Abstract Background The detection of circulating tumour cells (CTC) in blood sample in patients with early or advanced colorectal cancer has a potential prognostic value. Methods The challenge of CTC detection is related to the requirement of high sensitivity combined with high specificity method. CTCs detection can be distinguished between indirect and direct methods. The former ones are based on the recognition of tissue-, organ- or tumour-specific markers by immuno-histochemistry (indirect immuno-mediated methods) or (real-time) RT-PCR (indirect molecular methods), whilst the latter are related to CTCs selection based on the physical properties of density and sizes. Ongoing and future isolation by size of epithelial tumour cells (ISET) developments concerning automated image analysis on the filter and transmission of high definition images through the web for 'on line' cytopathological consultations are aimed to speed up the work of cytopathologists on CTC/ circulating tumour microemboli (CTM) detection. Conclusions CTC detection in colorectal cancer (CRC) correlates with pathological stage and clinical outcome in particular in those patients with advanced disease. CRC CTC level before and after CT are an independent prognostic factor for progression-free and overall survival. The positive prognostic value of complete clearance CTC after surgery may be useful to select patients for adjuvant chemotherapy

Anti-neuropathic effects of Rosmarinus officinalis L. terpenoid fraction: Relevance of nicotinic receptors

Traditional uses and current results highlight the neuroprotective properties of Rosmarinus officinalis L. The compelling need for novel strategies able to relieve neuropathic pain encouraged us to analyze different rosemary leaf extracts in rats following chronic constriction injury (CCI) of sciatic nerve. Ethanol, acetone, and the innovative ultrasound-hexane extractive methods were used to obtain: EE, AE, and for hexane extracts UREprel and URE. Extracts were characterized in terms of typical constituents and repeatedly administered to CCI-rats (13-days treatment, from the day of surgery). URE showed the best efficacy and potency in reducing hypersensitivity to noxious- and non-noxious stimuli and spontaneous pain. URE contained the higher quantity of the terpenoid carnosic acid (CA) and its efficacy was compared to pure CA. Histological analysis of the sciatic nerve revealed that URE prevented axon and myelin derangement, edema and inflammatory infiltrate. In the dorsal horn of the spinal cord, URE did not reduce astrocyte activation. Both the pain reliever and the neuroconservative effects of URE were significantly prevented by the nicotinic receptor (nAChR) antagonist mecamylamine. In conclusion, the hexane-ultrasound rosemary extract is able to reduce neuropathic hypersensitivity and protect nervous tissues. Effectiveness is mainly related to the terpenoid fraction by mechanisms involving nAChRs