• Effectiveness of cognitive behavioral therapy (CBT) for child and adolescent anxiety disorders across different CBT modalities and comparisons: a systematic review and meta-analysis.

  Sigurvinsdóttir, Anna Lilja; Jensínudóttir, Kolbrún Björk; Baldvinsdóttir, Karen Dögg; Smárason, Orri; Skarphedinsson, Gudmundur; 1 The Health Care Institution of North Iceland, Akureyri, Iceland. 2 Faculty of Psychology, University of Iceland, Reykjavik, Iceland. 3 Landspitali - the National University Hospital of Iceland, Reykjavik, Iceland. (Taylor & Francis, 2019-11-18)

  Aim: Pediatric Anxiety Disorders (AD) are common. Cognitive behavioral therapy (CBT) is one of two first-line treatments of youth AD and it has previously been shown to be superior to wait-list but not placebo therapy. This study consists of a systematic review and meta-analysis of the literature to assess the efficacy of CBT modalities in comparison to control contingencies for pediatric anxiety disorders.Methods: Studies were included if they were randomized controlled trials, and if CBT was manualized or modular, alone or in combination with medication. CBT was required to include behavioral treatment, exposure treatment, or cognitive elements. Eligible studies included participants aged 18 years or younger.Results: Eighty-one studies were included, with 3386 CBT participants and 2527 control participants. The overall results indicated that CBT is an effective treatment for childhood AD. The results showed that individual-based CBT is superior to wait-list and attention control. Group-based CBT is superior to wait-list control and treatment as usual. Remote-based CBT was superior to attention control and wait-list control. Family-based CBT was superior to treatment as usual, wait-list control, and attention control. Selective serotonin reuptake inhibitors were no more effective than individual-based CBT. Combination treatment was, however, more effective than individual-based CBT.Conclusion: To the best of our knowledge, no meta-analysis has thus far disentangled the effects of CBT modalities across various comparisons. This meta-analysis hence provides an important update to the literature on the efficacy of CBT for treating anxiety disorders in young people.
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  A standalone bioreactor system to deliver compressive load under perfusion flow to hBMSC-seeded 3D chitosan-graphene templates.

  Lovecchio, Joseph; Gargiulo, Paolo; Vargas Luna, Jose Luis; Giordano, Emanuele; Sigurjónsson, Ólafur Eysteinn; 1 Institute of Biomedical and Neural Engineering, Reykjavík University, Menntavegur 1, 101, Reykiavík, Iceland. joseph.lovecchio@unibo.it. 2 Laboratory of Cellular and Molecular Engineering "Silvio Cavalcanti" - Department of Electrical, Electronic and Information Engineering "Guglielmo Marconi" (DEI), University of Bologna, Via Cesare Pavese 50, 47522, Cesena, FC, Italy. joseph.lovecchio@unibo.it. 3 Advanced Research Center on Electronic Systems (ARCES), University of Bologna, Via Vincenzo Toffano 2/2, 40125, Bologna, Italy. joseph.lovecchio@unibo.it. 4 Institute of Biomedical and Neural Engineering, Reykjavík University, Menntavegur 1, 101, Reykiavík, Iceland. 5 Department of Science, Reykjavík University, Menntavegur 1, 101, Reykiavík, Iceland. 6 Center of Medical Physics and Biomedical Engineering, Medical University of Vienna, Waehringer Guertel 18-20/4L, 1090, Wien, Austria. 7 Laboratory of Cellular and Molecular Engineering "Silvio Cavalcanti" - Department of Electrical, Electronic and Information Engineering "Guglielmo Marconi" (DEI), University of Bologna, Via Cesare Pavese 50, 47522, Cesena, FC, Italy. 8 Advanced Research Center on Electronic Systems (ARCES), University of Bologna, Via Vincenzo Toffano 2/2, 40125, Bologna, Italy. 9 Health Sciences and Technologies - Interdepartmental Center for Industrial Research (HST-ICIR), University of Bologna, Via Tolara di Sopra 41/E, 40064, Ozzano dell'Emilia, BO, Italy. 10 The Blood Bank, The Landspitali University Hospital, Snorrabraut 60, 105, Reykjavík, Iceland. (Nature Publishing Group, 2019-11-14)

  The availability of engineered biological tissues holds great potential for both clinical applications and basic research in a life science laboratory. A prototype standalone perfusion/compression bioreactor system was proposed to address the osteogenic commitment of stem cells seeded onboard of 3D chitosan-graphene (CHT/G) templates. Testing involved the coordinated administration of a 1 mL/min medium flow rate together with dynamic compression (1% strain at 1 Hz; applied twice daily for 30 min) for one week. When compared to traditional static culture conditions, the application of perfusion and compression stimuli to human bone marrow stem cells using the 3D CHT/G template scaffold induced a sizable effect. After using the dynamic culture protocol, there was evidence of a larger number of viable cells within the inner core of the scaffold and of enhanced extracellular matrix mineralization. These observations show that our novel device would be suitable for addressing and investigating the osteogenic phenotype commitment of stem cells, for both potential clinical applications and basic research.
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  Decreasing and stabilising trends of antimicrobial consumption and resistance in and in segmented regression analysis, European Union/European Economic Area, 2001 to 2018.

  Penalva, German; Hogberg, Liselotte Diaz; Weist, Klaus; Vlahovic-Palcevski, Vera; Heuer, Ole; Monnet, Dominique L; Vandael, Eline; Ivanov, Ivan N.; Payerl-Pal, Marina; Skjold Selle Pedersen, Karoline; et al. (European Centre for Disease Prevention and Control (ECDC), 2019-11-01)

  Investments to reduce the spread of antimicrobial resistance (AMR) in the European Union have been made, including efforts to strengthen prudent antimicrobial use. Using segmented regression, we report decreasing and stabilising trends in data reported to the European Surveillance of Antimicrobial Consumption Network and stabilising trends in data reported to the European Antimicrobial Resistance Surveillance Network. Our results could be an early indication of the effect of prioritising AMR on the public health agenda.
• The demographics of persistent opioid consumption following limb amputation.

  Steen, Talora; Lirk, Philipp B; Sigurdsson, Martin I; 1 Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 2 Division of Anesthesia and Intensive Care Medicine, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. 3 Faculty of Medicine, University of Iceland, Reykjavik, Iceland. (Wiley, 2019-10-24)

  BACKGROUND: Patients who have limb amputation are at risk of chronic pain, including phantom limb pain that can be challenging to treat. The aim of this study was to describe the incidence of pre-operative opioid usage and the incidence and risk factors for new persistent post-operative opioid usage in opioid-naïve patients after limb amputation. METHODS: A retrospective study of all patients 18 years and older underwent upper or lower extremity amputations in Landspitali University Hospital between 2005 and 2015. Patients were considered to use opioids pre-operatively if they filled an opioid prescription 1-6 months prior to amputation and were considered to have persistent opioid use if opioid prescriptions were filled between post-operative months four to twenty-four. In addition to incidence estimate, uni- and multivariate analysis was performed to identify risk factors for persistent post-operative opioid usage. RESULTS: Of 328 total patients, 216 (66%) were opioid naïve and 112 (34%) were chronic opioid users. Of the opioid-naïve patients surviving more than 3 months 40 (20%) developed persistent post-operative opioid usage. In multivariate analysis, factors independently associated with persistent post-operative opioid usage were younger age, male gender, pre-operative use of neuropathic medications or benzodiazepines and lower (opposed to upper) extremity amputation. CONCLUSION: Opioid naïve patients undergoing major amputation had a 20% chance of having a persistent opioid requirement following surgery. This could represent new-onset phantom limb pain or other chronic pain. Our findings should encourage perioperative multimodal efforts to reduce the burden of chronic pain after limb amputations.
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  Epigenetic inactivation of the splicing RNA-binding protein CELF2 in human breast cancer.

  Piqué, Laia; Martinez de Paz, Alexia; Piñeyro, David; Martínez-Cardús, Anna; Castro de Moura, Manuel; Llinàs-Arias, Pere; Setien, Fernando; Gomez-Miragaya, Jorge; Gonzalez-Suarez, Eva; Sigurdsson, Stefan; et al. (Nature Publishing Group, 2019-11)

  Human tumors show altered patterns of protein isoforms that can be related to the dysregulation of messenger RNA alternative splicing also observed in transformed cells. Although somatic mutations in core spliceosome components and their associated factors have been described in some cases, almost nothing is known about the contribution of distorted epigenetic patterns to aberrant splicing. Herein, we show that the splicing RNA-binding protein CELF2 is targeted by promoter hypermethylation-associated transcriptional silencing in human cancer. Focusing on the context of breast cancer, we also demonstrate that CELF2 restoration has growth-inhibitory effects and that its epigenetic loss induces an aberrant downstream pattern of alternative splicing, affecting key genes in breast cancer biology such as the autophagy factor ULK1 and the apoptotic protein CARD10. Furthermore, the presence of CELF2 hypermethylation in the clinical setting is associated with shorter overall survival of the breast cancer patients carrying this epigenetic lesion.

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