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OBJECTIVES: Evidence regarding the cost-effectiveness of joint protection and hand exercises for the management of hand OA is not well established. The primary aim of this study is to assess the cost-effectiveness (cost-utility) of these management options. In addition, given the absence of consensus regarding the conduct of economic evaluation alongside factorial trials, we compare different analytical methodologies. METHODS: A trial-based economic evaluation to assess the cost-utility of joint protection only, hand exercises only and joint protection plus hand exercises compared with leaflet and advice was undertaken over a 12 month period from a UK National Health Service perspective. Patient-level mean costs and mean quality-adjusted life years (QALYs) were calculated for each trial arm. Incremental cost-effectiveness ratios (ICERs) were estimated and cost-effectiveness acceptability curves were constructed. The base case analysis used a within-the-table analysis methodology. Two further methods were explored: the at-the-margins approach and a regression-based approach with or without an interaction term. RESULTS: Mean costs (QALYs) were £58.46 (s.d. 0.662) for leaflet and advice, £92.12 (s.d. 0.659) for joint protection, £64.51 (s.d. 0.681) for hand exercises and £112.38 (s.d. 0.658) for joint protection plus hand exercises. In the base case, hand exercises were the cost-effective option, with an ICER of £318 per QALY gained. Hand exercises remained the most cost-effective management strategy when adopting alternative methodological approaches. CONCLUSION: This is the first trial evaluating the cost-effectiveness of occupational therapy-supported approaches to self-management for hand OA. Our findings showed that hand exercises were the most cost-effective option.

Background: Adherence to recommendations for osteoarthritis (OA) care can be measured using quality indicators (QI). In previous research differences related to the study design or the QI items make it challenging to directly compare the results. This EULAR funded study is the first that has applied the same set of QI items across four European countries. Objectives: To assess and compare patient perceived quality of OA management in primary health care in Denmark, Norway, Portugal, and the United Kingdom. Methods: Participants consulting general practitioners with clinical signs and symptoms of knee OA were identified in 30 general practices and invited to complete a cross-sectional survey including 14 QIs for OA care. A QI was considered as eligible if the participant had checked "Yes" or "No", and as achieved if the participant had checked "Yes" to the indicator. The median percentage of eligible QIs achieved by country was determined and compared using negative binomial regression analyses. Achievement of individual QIs by country was determined and compared using logistic regression analyses. Results: A total of 354 participants self-reported QI achievement. For the total sample, the median percentage of QIs achieved (checked 'Yes') was 48% (IQR 28% to 64%; range 0-100%). By country, the median percentage of QIs achieved was relatively similar across three of the countries, but significantly lower in Denmark (23%) compared to Norway (50%) even after adjustment for age, gender, BMI and comorbidity (rate ratio 0.49; 0.39, 0.62). For individual QIs related to different aspects of OA care, significant differences in self-reported achievement rates between the four countries were seen (Table 1). Achievement rates on individual QIs showed a large variation ranging from 0% ("referral to services for losing weight" & "functional assessments" in Denmark) to 83% ("information about the importance of exercise" in Norway). Compared to Norway, the achievement rates were significantly lower for 10 QIs in Denmark, 2 QIs in Portugal and 1 QI in the UK, whereas UK had significantly higher achievement rates than Norway for 5 QIs. Conclusions: The results revealed a potential for improvement in OA care in all four countries, but for somewhat different aspects of OA care. By exploring these differences and comparing health care services across countries, ideas may be generated on how the quality of OA care might be improved. Larger studies are needed to confirm and further explore the findings in this study. (Table Presented).

Objectives: Evidence regarding the cost-effectiveness of joint protection and hand exercises for the management of hand osteoarthritis (OA) is not well established. The primary aim of this study is to assess the cost-effectiveness (cost-utility) of these management options. In addition, given the absence of consensus regarding the conduct of economic evaluation alongside factorial trials, we compare different analytic methodologies. \ud \ud Methods: A trial-based economic evaluation to assess the cost-utility of joint protection only, hand exercises only and joint protection plus hand exercises compared with leaflet and advice was undertaken over a 12-month period, from a UK National Health Service (NHS) perspective. Patient-level mean costs and mean quality-adjusted life years (QALYs) were calculated for each trial arm. Incremental cost-effectiveness ratios (ICERs) were estimated and cost-effectiveness acceptability curves (CEACs) constructed. The base case analysis used a ‘within the table’ analysis methodology. Two further methods were explored: the ‘at the margins’ approach, and a regression-based approach with or without an interaction term. \ud \ud Results: Mean costs (QALYs) were £58.46 (0.662) for leaflet and advice, £92.12 (0.659) for joint protection, £64.51 (0.681) for hand exercises and £112.38 (0.658) for joint protection plus hand exercises. In the base case, hand exercises were the cost-effective option with an ICER of £318 per QALY gained. Hand exercises remained the most cost-effective management strategy when adopting alternative methodological approaches. \ud \ud Conclusion: This is the first trial evaluating the cost effectiveness of occupational therapy-supported approaches to self-management for hand OA. Our findings showed that hand exercises were the most cost-effective option.

Rumex thyrsiflorus Fingerh. is one of the few dioecious plant species, which have sex chromosomes. We conducted the preliminary experiments to determine the type of morphogenesis of R. thyrsiflorus explants cultured in vitro and to verify, using PCR-based methods, if there is the relationship between sex and morphogenetic response of explants micropropagated under in vitro conditions. The results of our studies revealed the female-biased sex ratios among explants cultured in vitro (M:F=1:1.7). The female-biased sex ratios in case of explants showed organogenesis in vitro (M:F=1:2.44) may suggest a higher regeneration ability of female explants.

This work was supported by Junta de Andalucia, project of Excellence from Junta de Andalucia P10-CTS-0662, P12-CTS-383 to FJO, Spanish Ministry of Economy and Competitiveness SAF2012-40011C02-01, SAF2015-70520-R, RTI2018-098968-B-I00, RTICC RD12/0036/0026 and CIBER Cancer ISCIII CB16/12/00421 to FJO. EB1s lab is supported by the Basque Department of Industry, Tourism and Trade (Etortek) and the MINECO (CB16/12/00421) grants. Fundacion Domingo Martinez (call 2019)., We would like to acknowledge Laura L´opez for technical assistance; Eduardo Andr´es and Laura Terr´on (Bioinformatic core IPBLN, CSIC) and Pan Hui (Bioinformatic Core, Joslin Diabetes center, Harvard Medical School)., Background: The adaptation to hypoxia is mainly controlled by the HIF transcription factors. Increased expression/ activity of HIF-1α correlates with poor prognosis in cancer patients. PARP-1 inhibitors are used in the clinic to treat BRCAness breast/ovarian cancer and have been shown to regulate the hypoxic response; therefore, their use could be expanded. Methods: In this work by integrating molecular/cell biology approaches, genome-wide ChIP-seq, and patient samples, we elucidate the extent to which PARP-1 exerts control over HIF-1-regulated genes. Results: In human melanoma, PARP-1 and HIF-1α expression are strongly associated. In response to a hypoxic challenge poly(ADP-ribose) (PAR) is synthesized, HIF-1α is post-transcriptionally modified (PTM) and stabilized by PARylation at specific K/R residues located at its C-terminus. Using an unbiased ChIP-seq approach we demonstrate that PARP-1 dictates hypoxia-dependent HIF-recruitment to chromatin in a range of HIF-regulated genes while analysis of HIF-binding motifs (RCGTG) reveals a restriction on the recognition of hypoxia responsive elements in the absence of PARP-1. Consequently, the cells are poorly adapted to hypoxia, showing a reduced fitness during hypoxic induction. Conclusions: These data characterize the fine-tuning regulation by PARP-1/PARylation of HIF activation and suggest that PARP inhibitors might have therapeutic potential against cancer types displaying HIF-1α overactivation., Junta de Andalucia P10-CTS-0662 P12-CTS-38, Spanish Ministry of Economy and Competitiveness SAF2012-40011-C02-01 SAF2015-70520- R RTI2018-098968-B-I00 RTICC RD12/0036/0026, CIBER Cancer ISCIII CB16/12/00421, Basque Department of Industry, Tourism and Trade (Etortek), MINECO CB16/12/00421, Fundacion Domingo Martinez