32,383 research outputs found

    –źmelioration by phytoadaptogene of effects of balneofactors of Truskavets‚Äô Spa on patients with post-radiation encephalopathy

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    Background.¬†We have previously explored effects of Ukrainian¬†phytocomposition ‚ÄúBalm Truskavets‚Äô‚Ä̬†on parameters of neuro-endocrine-immune complex and biophotonics in humans with maladaptation.¬†It is known that in patients with post-radiation encephalopathy the reaction to some stimuli is significantly changed, therefore it needs correction.¬†The purpose of this study is to test the ability of this phytocomposition to amelioration the effects of standard balneotherapeutic complex in patients with post-radiation encephalopathy.¬†Material and methods. The research was carried out through a retrospective analysis of the database of the Truskavetsian Scientific School of Balneology, which remained unpublished. The object of observation in 1997 were 19 men and 3 women with urate¬†urolithiasis and chronic pyelonephritis¬†who were exposed to pathogenic factors of the accident at the Ch–ĺrnobylian nuclear power plant during the liquidation of its consequences in 1986-87. The survey was conducted twice: on admission and after two weeks of rehabilitation in sanatorium ‚ÄúPerlyna Prykarpattya‚Ä̬†(Truskavets‚Äô Spa). 11 patients received standard balneotherapy¬†while¬†the other 11 patients additionally received the phytocomposition¬†‚ÄúBalm Truskavets‚Äô‚ÄĚ. According to the protocol, blood pressure,¬†routine hematological and biochemical blood parameters were determined. In addition, physical working capacity (PWC150)¬†as well as EEG, heart rate variability (HRV) and immunity parameters were determined.¬†Results. Standard balneotherapy increases the decreased level of T-helper lymphocytes, but further decreases the level of B-lymphocytes, glomerular filtration rate and PWC150, in combination with increased normal levels of blood creatinine and urea, as well as decreased levels of diastolic BP and heart rate.¬†This is accompanied by a further increase in the sympathetic tone and the leveling of the increased of ULF band HRV as marker of level in the plasma of catecholamines and glucocorticoids.¬†Additional use of phytocomposition limits the adverse effects of standard balneotherapy by modulating EEG and HRV parameters. Conclusion. Phytocomposition¬†"Balm¬†Truskavets'" by¬†modulating¬†the¬†parameters¬†of¬†the¬†nervous¬†system¬†limits¬†the¬†adverse¬†effects¬†of¬†standard¬†balneotherapy¬†at¬†the¬†Truskavets‚Äô¬†Spa¬†in¬†patients¬†with¬†post-radiation¬†encephalopathy

    EVALUACI√ďN ANALG√ČSICA PERIOPERATORIA DEL ACETAMINOF√ČN EN PERRAS SOMETIDAS A OVARIOHISTERECTOM√ćA ELECTIVA

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    Tesis de doctorado que eval√ļa el efecto analg√©sico del acetaminof√©n en perras ovarihisterectomizadas.La administraci√≥n de analg√©sicos antiinflamatorios no esteroidales (AINES) para el control del dolor post-quir√ļrgico en perros es una pr√°ctica com√ļn, debido a sus efectos analg√©sicos, antiinflamatorios y antipir√©ticos. En el presente trabajo se realizaron dos estudios. En el experimento 1, el objetivo fue evaluar la analgesia post-operatoria del acetaminof√©n (paracetamol) a trav√©s de la utilizaci√≥n de las escalas de reconocimiento cl√≠nico del dolor DIVAS (Escala Din√°mica e Interactiva Anal√≥gica Visual) y UMPS (Escala de la Universidad de Melbourne), en perras sometidas a ovariohisterectom√≠a electiva. Adem√°s de valorar la seguridad y eficacia cl√≠nica del uso del acetaminof√©n en perros mediante pruebas de funcionamiento hep√°tico y renal en el post-operatorio inmediato. Para ello, se utilizaron 30 perras de diferentes razas que fueron asignadas aleatoriamente a uno de los tres grupos de tratamiento: acetaminof√©n [GACET; n=10, 15 mg kg-1 intravenoso (IV)], carprofeno (GCARP; n=10, 4 mg kg-1 IV) y meloxicam (GMELOX; n=10, 0.2 mg kg-1 IV). Todos los tratamientos se administraron 30 minutos antes de la cirug√≠a y posterior a esta durante 48 horas. En este per√≠odo el acetaminof√©n se administr√≥ por v√≠a oral cada 8 horas (15 mg kg-1); el carprofeno (4 mg kg-1) y el meloxicam (0.1 mg kg-1) se administraron por v√≠a IV cada 24 horas. Durante el postoperatorio, los sistemas de puntuaci√≥n del dolor DIVAS y UMPS fueron medidos a las 1, 2, 4, 6, 8, 12, 16, 20, 24, 36 y 48 horas post-cirug√≠a. Para evaluar la seguridad cl√≠nica de los tratamientos, se recolectaron muestras de sangre de la vena yugular para realizar la medici√≥n de enzimas ALT, AST, ALP, y los metabolitos bilirrubina directa, bilirrubina indirecta, bilirrubina total, creatinina, urea, alb√ļmina y glucosa. Esto fue realizado en T0 (pre-anestesia; TBASAL), 48 y 96 horas despu√©s de la cirug√≠a (T48, T96). Los resultados indican que en la evaluaci√≥n cl√≠nica del dolor de todos los grupos de estudio, hubo una reducci√≥n gradual en la percepci√≥n del mismo durante el postoperatorio en ambos sistemas de puntuaci√≥n; no obstante, tambi√©n fue observado que ninguna escala difiri√≥ significativamente entre los tres grupos de tratamiento (P>0.05) en cada momento de evaluaci√≥n durante las 48 horas post-cirug√≠a. En cuanto a los par√°metros bioqu√≠mico s√©ricos, s√≥lo la ALT aument√≥ significativamente en T96 en el GACET y GCARP con respecto a los valores basales (P<0.01). El resto de los analitos s√©ricos evaluados se mantuvo en rangos normales. En el experimento 2 bajo el mismo dise√Īo experimental de tratamientos administrados, el objetivo fue evaluar el efecto analg√©sico perioperatorio del acetaminof√©n 2 administrado pre y post-quir√ļrgicamente en perras sometidas a ovariohisterectom√≠a electiva a trav√©s de la medici√≥n del √≠ndice de la actividad del tono parasimp√°tico (PTA). Este par√°metro hemodin√°mico fue medido 60 minutos antes de la cirug√≠a (TBASAL) y durante el transquir√ļrgico en la aplicaci√≥n de est√≠mulos nociceptivos: colocaci√≥n de las pinzas de campo backhouse (TPINZ), incisi√≥n de piel y abordaje quir√ļrgico primario (TINC), ligadura y extracci√≥n de ped√≠culo ov√°rico izquierdo (TOVI) y derecho (TOVD), ligadura y transfixi√≥n del cuello uterino (TLIGUT), secci√≥n quir√ļrgica del cuello uterino (TCUT), reconstrucci√≥n de peritoneo y planos anat√≥micos musculares (TMUSC) y sutura de piel (TSUT). Durante el postoperatorio, el √≠ndice PTA fue valorado a las 1, 2, 4, 6, 8, 12, 16, 20, 24, 36 y 48 horas, en los mismos tiempos en que fueron evaluadas las escalas de reconocimiento de dolor DIVAS y UMPS. Los resultados obtenidos en la medici√≥n del √≠ndice PTA basal para GACET fue 65 ¬Ī 8, para GCARP 65 ¬Ī 7 y para GMELOX 62 ¬Ī 5. Durante los diferentes tiempos transquir√ļrgicos, los valores promedio de √≠ndice PTA indican que GACET (76 ¬Ī 14) y GMELOX (72 ¬Ī 18) muestran tendencia a manifestar mayores niveles en comparaci√≥n con GCARP (62 ¬Ī 13) desde el inicio del procedimiento quir√ļrgico sin que esto pudiera comprobarse estad√≠sticamente, ya que no hubo diferencias significativas entre grupos de tratamiento ni entre los tiempos quir√ļrgicos evaluados (P>0.05). En el postoperatorio, el √≠ndice PTA fue de 65 ¬Ī 9 en el GACET, 63 ¬Ī 8 en el GCARP y 65 ¬Ī 8 en el GMELOX. Los resultados tampoco mostraron diferencias estad√≠sticamente significativas con los valores basales o entre los tratamientos (P>0.05). El √≠ndice PTA postoperatorio mostr√≥ una sensibilidad del 40%, especificidad del 98.46% y valor predictivo negativo del 99.07% con respecto a la escala validada de UMPS. En conclusi√≥n, el acetaminof√©n puede considerarse una herramienta para el tratamiento efectivo del dolor perioperatorio agudo en perros, ya que mostr√≥ la misma eficacia cl√≠nica que el meloxicam y el carprofeno para la analgesia postquir√ļrgica en perras sometidas a ovariohisterectom√≠a electiva. Adem√°s, la evidencia del uso de este medicamento no condujo a reacciones adversas o cambios en los par√°metros evaluados, lo que indica su seguridad cl√≠nica. Finalmente, destacar que el √≠ndice PTA representa una medici√≥n objetiva del comfort y analgesia postoperatoria, por lo que es una herramienta que podr√≠a ayudar a predecir las respuestas hemodin√°micas asociadas con el dolor

    Utiliza√ß√£o de plasma aut√≥logo no tratamento de √ļlceras da c√≥rnea no c√£o : estudo retrospetivo de 30 casos

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    Disserta√ß√£o de Mestrado Integrado em Medicina Veterin√°ria. √Ārea Cient√≠fica - Cl√≠nicaO plasma sangu√≠neo apresenta caracter√≠sticas semelhantes √†s da pel√≠cula lacrimal. Cont√©m componentes que, quando aplicados topicamente, promovem a regenera√ß√£o do tecido corneal e asseguram a sua integridade e viabilidade. Col√≠rios formulados a partir de sangue do paciente s√£o relativamente f√°ceis de obter e normalmente bem tolerados, sendo usados no tratamento de diversas doen√ßas oculares. Em √ļlceras de c√≥rnea complicadas, para al√©m de potenciar a cura, diminui ainda a atividade das colagenases envolvidas no processo. O presente estudo teve como objetivo realizar uma avalia√ß√£o retrospetiva sobre a utiliza√ß√£o de plasma aut√≥logo no tratamento de √ļlceras da c√≥rnea em c√£es. Para isso, foram avaliados pacientes diagnosticados com √ļlceras corneais no HRVM num per√≠odo de seis meses. Foi feita a caracteriza√ß√£o da amostra, da doen√ßa e do tratamento. Para determinar a efic√°cia da plasmaterapia, foram comparados os tempos medianos de cicatriza√ß√£o das les√Ķes superficiais tratadas com e sem plasma. Para defeitos graves (indolentes e profundos), estes tempos foram correlacionados de acordo com a frequ√™ncia da administra√ß√£o. Recorreu-se a uma an√°lise de sobreviv√™ncia para tratamento estat√≠stico destes dados. A amostra incluiu 30 c√£es de 14 ra√ßas distintas, maioritariamente braquic√©falas (70%). A idade m√©dia foi de 6.69 ¬Ī 4.03 anos (compreendida entre 0.17-14 anos). 43.33% (n=13) das les√Ķes eram estromais e 56.67% (n=17) afetaram apenas o epit√©lio. Destas, 40% (n=12) responderam ao tratamento e 16.67% (n=5) tiveram um comportamento indolente. A maioria das √ļlceras superficiais n√£o era extensa (n=6; 50%) e as profundas eram predominantemente vastas e mal√°cicas (n=4; 30.77%). O tratamento variou, tendo sido aplicado plasma aut√≥logo em 5 das 12 les√Ķes superficiais e em todas as graves (n=18). N√£o se encontraram diferen√ßas estatisticamente significativas entre os tempos medianos de recupera√ß√£o das les√Ķes superficiais tratadas com e sem plasma (Kaplan Meier; p=0.9), nem entre os tempos de cura dos defeitos graves de acordo com a frequ√™ncia de administra√ß√£o (Kaplan Meier; p=0.9). No presente estudo n√£o foram observados efeitos adversos decorrentes da utiliza√ß√£o de col√≠rios de plasma aut√≥logo, tendo sido demonstrado ser um produto bem tolerado pelos pacientes. N√£o foi poss√≠vel obter resultados estatisticamente significativos que comprovem a sua efic√°cia, devido √† heterogeneidade da amostra, diferen√ßas nos protocolos terap√™uticos adotados e aus√™ncia de grupos controlo. Estudos adicionais poder√£o contribuir para evidenciar os seus benef√≠cios terap√™uticos.ABSTRACT - Use of autologous plasma in the treatment of corneal ulcers in the dog: a retrospective study of 30 cases - Blood plasma presents characteristics similar to those of the tear film. It contains components that, when applied topically, promote corneal tissue regeneration and ensure its integrity and viability. Eye drops formulated from the patient's blood are relatively easy to obtain and usually well tolerated, and are used in the treatment of various ocular diseases. In complicated corneal ulcers, not only enhances healing but also decreases the activity of the collagenases involved in the process. The present study aimed to perform a retrospective evaluation on the use of autologous plasma in the treatment of corneal ulcers in dogs. Patients diagnosed with corneal ulcers at the HRVM were evaluated over a six-month period. Characterization of the sample, disease and treatment was performed. To determine the efficacy of plasmatherapy, median healing times of superficial lesions treated with and without autologous plasma were compared. For severe defects (indolent and deep) these times were correlated according to the administration frequency. Survival analysis was used for statistical treatment of these data. The sample included 30 dogs of 14 different breeds, mostly brachycephalic (70%). The mean age was 6.69¬Ī4.03 years (range 0.17-14 years). 43.33% (n=13) of the lesions were stromal and 56.67% (n=17) affected the epithelium only. From these, 40% (n=12) responded to treatment and 16.67% (n=5) had an indolent behavior. The majority of the superficial ulcers were not extense (n=6; 50%) and the deep ones were predominantly wide and melting (n=4; 30.77%). The treatment varied, with plasma being applied to 5 of the 12 superficial lesions and in all (n=18) severe ulcers. Median recovery times for superficial lesions treated with or without plasma were compared (Kaplan Meier; p=0.9) as well as healing times in severe defects according to the frequency of administration (Kaplan Meier; p=0.9). No significant statistical differences were found. In the present study, no adverse effects from the use of autologous plasma eye drops were observed, having been shown to be a product well tolerated by patients. It was not possible to obtain statistically significant results that prove its efficacy, due to the heterogeneity of the sample, differences in the therapeutic protocols adopted and the absence of control groups. Further studies may contribute to evidence its therapeutic benefits.N/

    In vitro investigation of the effect of disulfiram on hypoxia induced NFőļB, epithelial to mesenchymal transition and cancer stem cells in glioblastoma cell lines

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    A thesis submitted in partial fulfilment of the requirements of the University of Wolverhampton for the degree of Doctor of Philosophy.Glioblastoma multiforme (GBM) is one of the most aggressive and lethal cancers with a poor prognosis. Advances in the treatment of GBM are limited due to several resistance mechanisms and limited drug delivery into the central nervous system (CNS) compartment by the blood-brain barrier (BBB) and by actions of the normal brain to counteract tumour-targeting medications. Hypoxia is common in malignant brain tumours such as GBM and plays a significant role in tumour pathobiology. It is widely accepted that hypoxia is a major driver of GBM malignancy. Although it has been confirmed that hypoxia induces GBM stem-like-cells (GSCs), which are highly invasive and resistant to all chemotherapeutic agents, the detailed molecular pathways linking hypoxia, GSC traits and chemoresistance remain obscure. Evidence shows that hypoxia induces cancer stem cell phenotypes via epithelial-to-mesenchymal transition (EMT), promoting therapeutic resistance in most cancers, including GBM. This study demonstrated that spheroid cultured GBM cells consist of a large population of hypoxic cells with CSC and EMT characteristics. GSCs are chemo-resistant and displayed increased levels of HIFs and NFőļB activity. Similarly, the hypoxia cultured GBM cells manifested GSC traits, chemoresistance and invasiveness. These results suggest that hypoxia is responsible for GBM stemness, chemoresistance and invasiveness. GBM cells transfected with nuclear factor kappa B-p65 (NFőļB-p65) subunit exhibited CSC and EMT markers indicating the essential role of NFőļB in maintaining GSC phenotypes. The study also highlighted the significance of NFőļB in driving chemoresistance, invasiveness, and the potential role of NFőļB as the central regulator of hypoxia-induced stemness in GBM cells. GSC population has the ability of self-renewal, cancer initiation and development of secondary heterogeneous cancer. The very poor prognosis of GBM could largely be attributed to the existence of GSCs, which promote tumour propagation, maintenance, radio- and chemoresistance and local infiltration. In this study, we used Disulfiram (DS), a drug used for more than 65 years in alcoholism clinics, in combination with copper (Cu) to target the NFőļB pathway, reverse chemoresistance and block invasion in GSCs. The obtained results showed that DS/Cu is highly cytotoxic to GBM cells and completely eradicated the resistant CSC population at low dose levels in vitro. DS/Cu inhibited the migration and invasion of hypoxia-induced CSC and EMT like GBM cells at low nanomolar concentrations. DS is an FDA approved drug with low toxicity to normal tissues and can pass through the BBB. Further research may lead to the quick translation of DS into cancer clinics and provide new therapeutic options to improve treatment outcomes in GBM patients

    An investigation of the relationship between perioperative characteristics and perioperative anaesthesia on the postoperative systemic inflammatory response and clinical outcome in patients undergoing surgery for colorectal cancer

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    In UK, colorectal cancer (CRC) is the fourth most common cancer and the second most common cause of cancer death. Until now, surgical resection remains the cornerstone for the management of CRC in all stages, however, stress response elicit from surgery may cause different changes through multiple systems in human body including neural, endocrine, metabolic, inflammatory, and immunological changes. In addition, other perioperative factors such as volatile anaesthetic and opioids may induce the immunosuppression. There is a proportional correlation between the stress response and the magnitude of the inflammatory immune response, invasiveness, and duration of surgery. The pre-operative and post-operative status of patients are important when considering the prognosis. The systemic inflammatory response (SIR) has been recognised to correlate with tumour progression and the prognosis of CRC. An exaggerated postoperative SIR is associated with postoperative infective complications and poor survival. Several predictive markers of the SIR have been used, such as the neutrophil to lymphocyte ratio (NLR), serum C-reactive protein (CRP) level, and Glasgow prognostic score (GPS). Some evidence reported that general anaesthesia (GA) combined with regional anaesthesia (RA) are better than the single use of general anaesthesia in reducing the post-operative immuno-suppression in some degrees. Furthermore, the peri-operative inflammatory process may be affected by the choice of anaesthetic technique, with propofol reported to have anti-inflammatory effect by targeting neutrophil activity. Up to now, there is insufficient evidence to recommend any specific anaesthetic or analgesic technique for patients undergoing surgery for tumour resection based on inflammatory response, recurrence, and metastasis. The work presented in this thesis further examines the relationship between the perioperative characteristics, perioperative anaesthesia, and the postoperative systemic inflammatory response following surgery for colorectal cancer. Several preoperative medications along with anaesthesia might influence the postoperative systemic inflammatory response but the question is whether the post-operative systemic inflammatory response affected by the administration of different types of anaesthesia or not following surgery for colorectal cancer. Chapter 1 discusses the epidemiology, aetiology, carcinogenesis, risk factors of colorectal cancer, pro-carcinogenic factors, anti-carcinogenic agents, inflammation and cancer, the post-operative systemic inflammatory response, tumour staging, screening, and diagnosis of colorectal cancer. Chapter 2 discusses the treatment of colorectal cancer. Chapter 3 discusses different anaesthetic techniques and agents. Chapter 4 provides summary and aims of the thesis. Chapter 5 represents findings from a systematic review and meta-analysis about the effect of anaesthesia on the postoperative systemic inflammatory response in patients undergoing surgery. The results conclude that there was some evidence that anaesthetic regimens may reduce the magnitude of the post-operative SIR. However, the studies identified in this systematic review were heterogeneous and generally of low quality. Chapter 6 represents a retrospective cohort study about the relationship between anaesthetic technique, clinicopathological characteristics and the magnitude of the postoperative systemic inflammatory response in patients undergoing elective surgery for colon cancer. The results show that the type of anaesthesia varied over time and appears to influence the magnitude of the postoperative SIR on post-operative day 2 for those patients who underwent for open surgery but not laparoscopic surgery. Chapter 7 represents a prospective cohort study about the effect of anaesthesia on the magnitude of the postoperative systemic inflammatory response in patients undergoing elective surgery for colorectal cancer in the context of an enhanced recovery pathway. The results show that there was a modest but an independent association between regional anaesthesia (RA) and a lower magnitude of the postoperative SIR. Chapter 8 represents the relationship between pre-operative medications, the type of anaesthesia and post-operative sequelae in patients undergoing surgery for colorectal cancer. The results show that there was no association between the preoperative administration of aspirin, statins and ACE inhibitors and anaesthesia. Chapter 9 represents the relationship between nutritional status, anaesthetic approach, and peri-operative characteristics of patients undergoing surgery for colorectal cancer. The results show that there was no significant association between measures of nutritional status and anaesthetic approach. Chapter 10 represents the relationship between opioid administration, type of anaesthesia and clinicopathological characteristics in patients undergoing surgery for colorectal cancer. The results show that opioid administration was independently associated with both anaesthetic and operative factors. Chapter 11 represents the main findings of the thesis and some recommendation for a future work

    Epilepsy Mortality: Leading Causes of Death, Co-morbidities, Cardiovascular Risk and Prevention

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    a reuptake inhibitor selectively prevents seizure-induced sudden death in the DBA/1 mouse model of sudden unexpected ... Bilateral lesions of the fastigial nucleus prevent the recovery of blood pressure following hypotension induced by&nbsp;..

    Innate immunity and metabolism in the bovine ovarian follicle

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    Postpartum uterine disease in dairy cows is associated with reduced fertility. One of the first and most prevalent bacteria associated with uterine disease is Escherichia coli. The bacterial endotoxin, lipopolysaccharide (LPS), accumulates in the ovarian follicular fluid of animals with uterine disease. The granulosa cells of the ovarian follicle respond to LPS by secreting pro-inflammatory cytokines, such as interleukin (IL)-1a, IL-1b and IL-8, and oocyte health is perturbed. Dairy cows also experience metabolic energy stress in the postpartum period, which is associated with an increased risk of developing uterine disease and ovarian dysfunction. This thesis explored the crosstalk between innate immunity and metabolic energy stress in bovine granulosa cells and cumulus-oocyte complex. Firstly, we found that glycolysis, AMP-activated protein kinase and the mechanistic target of rapamycin, regulate the innate immune responses to LPS in granulosa cells isolated from bovine ovarian follicles. Activation of AMP-activated protein kinase decreased the LPS-induced secretion of IL-1a, IL-1b, and IL8, and was associated with shortened duration of ERK1/2 and JNK phosphorylation. Next, we found that decreasing the availability of cholesterol or inhibiting cholesterol biosynthesis using short-interfering RNA impaired the LPS-induced secretion of IL-1a and IL-1b by granulosa cells. Furthermore, metabolic energy stress or inhibiting cholesterol biosynthesis in the bovine cumulus-oocyte complex modulated the innate immune responses to LPS, and perturbed meiotic progression during in vitro maturation. Finally, we explored an in vivo model of uterine disease in heifers, using RNAseq to investigate alterations to the transcriptome of the reproductive tract. We found that uterine disease altered the transcriptome of the endometrium, oviduct, granulosa cells and oocyte, several months after bacterial infusion; these changes were most evident in the granulosa cells and oocyte of the ovarian follicle. The findings from this thesis imply that there is crosstalk between innate immunity and metabolism in the bovine ovarian follicle

    The Challenges of Outcomes-Based Contract Implementation for Medicines in Europe

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    Objectives To outline the challenges of implementing Outcomes-Based Contracts (OBCs) in Europe. Methods A scoping review was conducted, building on the searches of a previous systematic review and updating them for December 2017 until May 2021. The combined results were screened, based on inclusion and exclusion criteria. All identified studies published in the English language that described specific OBC schemes for medicines in European countries were included. Insights into the challenges of OBC were extracted and analysed to develop a conceptual framework. Results Ten articles from the previous systematic review matched our inclusion criteria, along with fourteen articles from electronic searches. Analysis of these 24 articles and classification of the challenges revealed that there are multiple barriers which must be overcome if OBCs that benefit all stakeholders are going to be adopted widely across Europe. These challenges were grouped according to five key themes: negotiation framework; outcomes; data; administration and implementation; and laws and regulation.Conclusions If the promise of OBCs is to be fully realised in Europe, there remain major challenges that need to be overcome by all stakeholders working in partnership. The overlapping and interconnected nature of these challenges highlights the complexity of OBC arrangement
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