IntroductionTo investigate whether respiratory variation of inferior vena cava diameter (cIVC) predict fluid responsiveness in spontaneously breathing patients with acute circulatory failure (ACF).MethodsForty patients with ACF and spontaneous breathing were included. Response to fluid challenge was defined as a 15% increase of subaortic velocity time index (VTI) measured by transthoracic echocardiography. Inferior vena cava diameters were recorded by a subcostal view using M Mode. The cIVC was calculated as follows: (Dmax - Dmin/Dmax) × 100 and then receiver operating characteristic (ROC) curves were generated for cIVC, baseline VTI, E wave velocity, E/A and E/Ea ratios.ResultsAmong 40 included patients, 20 (50%) were responders (R). The causes of ACF were sepsis (n = 24), haemorrhage (n = 11), and dehydration (n = 5). The area under the ROC curve for cIVC was 0.77 (95% CI: 0.60-0.88). The best cutoff value was 40% (Se = 70%, Sp = 80%). The AUC of the ROC curves for baseline E wave velocity, VTI, E/A ratio, E/Ea ratio were 0.83 (95% CI: 0.68-0.93), 0.78 (95% CI: 0.61-0.88), 0.76 (95% CI: 0.59-0.89), 0.58 (95% CI: 0.41-0.75), respectively. The differences between AUC the ROC curves for cIVC and baseline E wave velocity, baseline VTI, baseline E/A ratio, and baseline E/Ea ratio were not statistically different (p = 0.46, p = 0.99, p = 1.00, p = 0.26, respectively).ConclusionIn spontaneously breathing patients with ACF, high cIVC values (>40%) are usually associated with fluid responsiveness while low values (< 40%) do not exclude fluid responsiveness.

1. As marked lability of bronchial obstruction is a risk factor for asthma severity, it may influence dyspnoea, the most common subjective complaint in asthma. We therefore studied the relationship between spontaneous dyspnoea and the degree of bronchial lability, as assessed by the daily variability in peak expiratory flow rate and the bronchial responsiveness to either carbachol or salbutamol, in 33 stable symptomatic asthmatic patients. 2. Three times daily, for 10 consecutive days, the patients rated the intensity of their dyspnoea on a visual analogue scale and immediately afterwards recorded their peak expiratory flow rate. Within the next 5 days, we determined the bronchial response by measuring the forced expiratory volume in 1 s and the specific resistance of airways to either carbachol or salbutamol according to baseline airway obstruction. 3. We characterized dyspnoea for each patient by using two parameters: (1) the relationship with underlying airway obstruction, as assessed by the correlation coefficient r between dyspnoea scores and corresponding values of peak expiratory flow rate (r DSc-PEFR), and (2) the intensity, as assessed by the mean visual analogue scale dyspnoea score adjusted for comparable airway obstruction. Bronchial lability was characterized by (1) variability in mean daily peak expiratory flow rate and (2) bronchial responsiveness to either carbachol (as assessed by the threshold dose and the slope of the dose-response curve) or salbutamol (as assessed by the threshold dose and maximal response). We assessed the relationship between dyspnoea and bronchial lability by correlating each of their respective characteristics. 4. We found large inter-subject differences in both characteristics of dyspnoea.(ABSTRACT TRUNCATED AT 250 WORDS)

Objectives: The Tunisian National Authority for Assessment and Accreditation has published in 2018 its first HTA report, aimed at informing the national payer on the effectiveness and cost-effectiveness of trastuzumab, the first agent targeting HER2 positive breast cancer, representing its biggest budgetary expenditure since 2008. Methods: A systematic litterature review of recent clinical practice guidelines on management of breast cancer was performed to extract best available evidence on effectiveness and risks related to trastuzumab. The recommendations of the Tunisian Society of Oncology were compared with SIGN and NICE guidelines. A benchmark of ex-factory prices of trastuzumab in different countries was carried out along with a survey among INAHTA members to collect prices' information, reimbursement and treatment management modalities. To determine the cost effectiveness of trastuzumab at the 2018 selling price, an adaptation of a Latin American cost-effectiveness study was conducted, followed by a sensitivity analysis and the estimation of the cost effectiveness price. Results: Trastuzumab significantly improves DFS and OS compared to chemotherapy alone, however it increases the risk of congestive heart failure. According to the benchmark, the 2018 ex-factory price of trastuzumab in Tunisia remains higher than most of high income countries. From the ministry of health's perspective, the ICER of trastuzumab was 49 670,67 USD/QALY, representing 4,5 times the 3 GDPPC/QALY threshold suggested by WHO. From the national payer's perspective, the ICER was 75 386,18 USD/QALY, representing 6,8 times the threshold. Probabilistic sensitivity analysis showed 0 % probability of trastuzumab being costeffective considering the same threshold. A discount of 78% on trastuzumab's acquisition price is required to reach cost-effectiveness threshold. These results provided a set of recommendations for the payer and informed the negociation of the biosimilar's price. Conclusions: This first INEAS HTA report clearly illustrates the central role of HTA at informing decision-makers in terms of price negotiations and reimbursement decisions.

A479the 6 new oncology drugs reimbursed by AIFA in 2014 with average times from the national reimbursement decision to the regional one ranging from 3 months in Piemonte to 5 months in Emilia Romagna. The Lazio and Sardinia Regions have evaluated only 1 out of the 6 drugs with an access time of around 2.5 and 6 months, respectively. ConClusions: In Italy, the average times from the national reimbursement decisions to the regional evaluations aiming to the formulary inclusion vary widely between Regions.

OBJECTIVES: A systematic review on 180 NICE oncology submissions identified three main network meta-analysis (NMA) methods; (1) Hazard ratio NMAs (HRNMA); (2) parametric survival NMAs (PNMA); and (3) fractional polynomial NMAs (FPNMA). This study aims to compare these NMA methods. METHODS: For comparing the NMA methods, three datasets with two trials were considered. The first NMA dataset considered trials in which proportional hazard (PH) holds. In the second, PH-assumption was violated in one trial. In the third, the PHassumption was violated and there was a sudden change in hazard. For the PNMA, Weibull, Lognormal and Loglogistic distributions were assessed. Secondorder FPs were assessed by varying P1 and P2 from -2.0 to +2.0. Best fitting models were selected on DIC. Outcomes were compared in terms of restricted mean survival (RMST) over the trial period and predicted mean survival. RESULTS: In the second dataset, the observed RMSTs of the first trial were 27.12 and 19.90 months. The RMSTs with HRNMA were 27.90 and 20.48 month; PNMA 28.00 and 20.44 months; and FPNMA 28.66 and 21.13 months, respectively. The observed RMSTs in the second trial (PH violated) were 12.35 and 10.51 months. The RMSTs with HRNMA were 13.22 and 10.51 months; PNMA 12.96 and 10.57 months; and FPNMA 12.52 and 11.24 months, respectively. Despite visual fit, RMSTs were similar. Mean incremental survival with HRNMA and PNMA in first trial were