Adolescent brain development seems to be important for the maturation of brain structures and behavior. Intermittent binge ethanol drinking is common among adolescents, and this type of drinking can induce brain damage and cognitive deficits. In addition, emotional changes are frequently seen in alcoholics and rodents treated with ethanol. Considering the close relation between emotional arousal and cognitive responses, the present work investigates if intermittent ethanol binge exposure could differentially alter the performance of adolescent rats in aversive and non-aversive motivated tests. Male adolescent rats were submitted to ethanol treatment (2.5 or 5.0 g/Kg, o.a.) at 48-h intervals over postnatal day (PND) 30 to 60. Control animals were exposed to a similar administration protocol with saline administration. At PND61-PND63 animals were submitted to one-trial object recognition or contextual and tone fear conditioning paradigms. Binge ethanol drinking (at both 2.5 and 5.0 g/Kg) did not change freezing response in the contextual and tone fear conditioning. However, all doses impaired recognition rates 24h after training in object recognition test. In addition, despite a diminution of horizontal locomotion in the open field (only for the 5.0 g/Kg dose), no difference was detected regarding time in immobility, time in grooming and number of rearing in this paradigm. The present results show that the cognitive impairment resulting from intermittent binge ethanol exposure has a negative correlation with learning-associated emotional arousal Keyword: ethanol, binge drinking, adolescent rats, learning and memory, emotional arousal.

Adolescent brain development seems to be important for the maturation of brain structures and behavior. Intermittent binge ethanol drinking is common among adolescents, and this type of drinking can induce brain damage and cognitive deficits. In addition, emotional changes are frequently seen in alcoholics and rodents treated with ethanol. Considering the close relation between emotional arousal and cognitive responses, the present work investigates if intermittent ethanol binge exposure could differentially alter the performance of adolescent rats in aversive and non-aversive motivated tests. Male adolescent rats were submitted to ethanol treatment (2.5 or 5.0 g/Kg, o.a.) at 48-h intervals over postnatal day (PND) 30 to 60. Control animals were exposed to a similar administration protocol with saline administration. At PND61-PND63 animals were submitted to one-trial object recognition or contextual and tone fear conditioning paradigms. Binge ethanol drinking (at both 2.5 and 5.0 g/Kg) did not change freezing response in the contextual and tone fear conditioning. However, all doses impaired recognition rates 24h after training in object recognition test. In addition, despite a diminution of horizontal locomotion in the open field (only for the 5.0 g/Kg dose), no difference was detected regarding time in immobility, time in grooming and number of rearing in this paradigm. The present results show that the cognitive impairment resulting from intermittent binge ethanol exposure has a negative correlation with learning-associated emotional arousal Keyword: ethanol, binge drinking, adolescent rats, learning and memory, emotional arousal.

To evaluate the cost-effectiveness of intravitreal aflibercept 2 mg every 8 weeks after 3 initial monthly doses (IVT-AFL 3+Q8) versus Ranibizumab 0.5 mg monthly (RAN Q4) and pro re nata after 3 initial monthly doses (RAN 3+PRN) in the treatment of patients with Neovascular Age-related Macular Degeneration (nAMD) from a Chinese payer's perspective, so as to provide evidence to support rational drug use in clinical practice in China. Methods: A Markov model was developed to simulate the progression of the disease in terms of visual acuity. The model included health status of "no visual impairment", "mild visual impairment", "moderate visual impairment", "severe vision loss", "blindness", and "death". Transition probabilities and utility scores were derived from published literature. Cost data were collected from medical institutions and physician surveys. Costs and QALYs were discounted at 5.0% per year. One-way sensitivity analyses were conducted. Results: For the lifetime horizon, the costs of IVT-AFL 3+Q8, RAN Q4 and RAN 3+PRN were 129,676.18 CNY, 164,903.36 CNY and 135,912.20 CNY respectively. The corresponding qualityadjusted life years (QALYs) were 6.162 QALYs, 6.162 QALYs and 6.156 QALYs. IVT-AFL 3+Q8 was dominant vs. RAN Q4 vs. RAN 3+PRN groups since it was cost saving (same outcome 6.162 QALYs with less costs). Sensitivity analyses showed that this result was robust. Conclusions: IVT-AFL 3+Q8 was similarly or more effective in terms of QALYs and less costly compared with RAN Q4 and RAN 3+PRN for nAMD patients in China.

66 Background: This systematic review and meta-analysis compared incremental cost-effectiveness ratios (ICERs) of cancer drugs and their relationship with society’s willingness to pay (WTP) across different countries, scenarios and indications. Methods: We sought for cost-effectiveness studies in PubMed, Embase, Cochrane and LILACS published from December 2012 to December 2017. CAR-T cell therapies were excluded given short follow-up. We converted ICERs value and respective annualized 1time the Gross Domestic Product per capita (GDP) - used as a proxy for WTP threshold - into purchase-parity-power dollars (PPP) for better economic reality comparisons. Economics data came from the International Monetary Fund website. Characteristics studied in the distribution of ICERs values were compared using the Mann-Whitney or Kruskal-Wallis U-test with multiple comparison correction and simple linear regression. The chance of ICER being below the 1x GDP threshold was expressed as odds ratio and 95% confidence interval, calculated by logistic regression. Results: We retrieved 354 drug-versus-drug different assessments. PPPconversion increased median ICER of middle-income countries ($32k to $68k;P < 0.001). Median ICER was highest in USA ($154k), followed by other high-income countries ($76k; P < 0.001). In multiple regression, anti-VEGF (P < 0.001) and US-led (P = 0.03) studies had highest ICERs, while curative therapies (p = 0.02) had the lowest ones. 22% of studies were below the WTP bar, none of anti-VEGF, sipuleucel, anti-CD-30, castration-resistant, hepatocarcinoma, and renal cell ones. Immune checkpoint inhibition (OR 8.70; P = 0.045) and middle-income (OR 7.40; P < 0.001) studies were more likely above WTP, whereas curative therapies were more likely below WTP. Conclusions: Cancer therapies’ cost exceeding the WTPs is a worldwide pattern, with some factors related to ICER variation. These findings may foster better understanding and aid stakeholders deal with the global issue of high oncology care costs.