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Intravenous maintenance fluid therapy (IV-MFT) is probably the most prescribed drug in paediatric hospital care. Recently paediatric societies have produced evidence-based practice guidelines that recommend the use of balanced isotonic fluid when prescribing IV-MFT in both acute and critical paediatric care. Unfortunately, the applicability of these guidelines could be called into question when a ready-to-use glucose-containing balanced isotonic fluid is not available. The main objective of this study was to describe the availability of glucose-containing balanced isotonic fluids in European and Middle Eastern paediatric acute and critical care settings. This work is an ancillary study of the survey dedicated to IV-MFT practices in the paediatric acute and critical care settings in Europe and Middle East, a cross-sectional electronic 27-item survey, emailed in April-May 2021 to paediatric critical care physicians across 34 European and Middle East countries. The survey was developed by an expert multi-professional panel within the European Society of Peadiatric and Neonatal Intensive Care (ESPNIC). Balanced isotonic fluid with glucose 5% was available for only 32/153 (21%) responders. Balanced isotonic fluid with glucose 5% was consistently available in the UK (90%) but not available in France, Greece, The Netherlands and Turkey.    Conclusion: Ready-to-use isotonic balanced IV solutions containing glucose in sufficient amount exist but are inconsistently available throughout Europe. National and European Medication Safety Incentives should guarantee the availability of the most appropriate and safest IV-MFT solution for all children. What is Known: • Intravenous maintenance fluid therapy (IV-MFT) is probably the most prescribed drug in paediatric hospital care. • Balanced isotonic fluid is recommended when prescribing IV-MFT in both acute and critical paediatric care. What is New: • Balanced isotonic fluid with glucose 5% is available for less than 25% of the prescribers in Europe and the Middle East. Availability of balanced isotonic fluid with glucose 5% varies from one country to another but can also be inconsistent within the same country. • Clinicians who have access to a ready-to-use balanced isotonic fluid with glucose 5% are more likely to consider its use than clinicians who do not have access to such an IV solution., (© 2024. The Author(s).)

Objective: Understanding preferences of patients with rheumatoid arthritis (RA) can facilitate tailored patient-centric care. This study elicited trade-offs that patients with RA were willing to make during treatment selection., Methods: Patients with RA completed an online discrete choice experiment, consisting of a series of choices between hypothetical treatments. Treatment attributes were selected based on literature review and qualitative patient interviews. Eligible patients were ≥18 years old, diagnosed with RA, receiving systemic disease-modifying antirheumatic drug therapy, and residents of Europe or USA. Male patients were oversampled for subgroup analyses. Data were analysed using a correlated mixed logit model., Results: Of 2090 participants, 42% were female; mean age was 45.2 years (range 18-83). Estimated effects were significant for all attributes (p<0.001) but varied between patients. Average relative attribute importance scores revealed different priorities (p<0.001) between males and females. While reducing pain and negative effect on semen parameters was most important to males, females were most concerned by risk of blood clots and serious infections. No single attribute explained treatment preferences by more than 30%. Preferences were also affected by patients' age: patients aged 18-44 years placed less importance on frequency and mode of treatment administration (p<0.05) than older age groups. Patients were willing to accept higher risk of serious infections and blood clots in exchange for improvements in pain, daily activities or administration convenience. However, acceptable trade-offs varied between patients (p<0.05)., Conclusion: Treatment preferences of patients with RA were individual-specific, but driven by benefits and risks, with no single attribute dominating the decision-making., Competing Interests: Competing interests: RA, consultancy fees from AbbVie, Amgen, Biogen, Bristol Myers Squibb, Celltrion, Gilead, Janssen, Lilly, Medac, MSD, Mylan, Novartis, Pfizer, Roche, Sandoz, Sanofi-Genzyme, UCB, VIATRIS. JCNG, consultancy fees from Lilly, Janssen, Amgen, GSK, AbbVie, Galápagos, MSD; speakers fees from MSD, Pfizer, BMS, AbbVie, UCB Pharma, Janssen, Lilly, Faes Farma, Roche, Celgene, Sanofi, Nordic Pharma, Gebro, Novartis, Biogen, Amgen, Sandoz. PJ, grants support from Pfizer and Roche; speakers fees from Eli Lilly; support for meeting attendance from Galapagos. CM, consultancy fees from BMS, AbbVie, Gilead; speakers fees from BMS, AbbVie, Eli Lilly, Pfizer, Boehringer, Galapagos, Sanofi, Roche. RM, grant support from Novartis; consultancy fees from Ferring; speakers fees from Amgen and Galapagos. HR, speakers fees from Gilead Science, Merck Sharp; Pfizer Cooperation Austria, Janssen. HEV, grants from Galapagos, Boehringer Ingelheim; speakers fees from Galapagos, AbbVie, Boehringer Ingelheim, Novartis, Pfizer, UCB, Janssen. SH, employee of Evidera Inc, which is part of Thermo Fisher Scientific's Clinical Research Group; Evidera received payment for conducting the work outlined in this manuscript; SH is a minority stockholder of Thermo Fisher Scientific, as part of his employment with Evidera. CW, employee of Evidera Inc, which is part of Thermo Fisher Scientific's Clinical Research Group; Evidera received payment for conducting the work outlined in this manuscript. NK, employee of Evidera Inc, which is part of Thermo Fisher Scientific's Clinical Research Group; Evidera received payment for conducting the work outlined in this manuscript; NK is a minority stockholder of Thermo Fisher Scientific, as part of his employment with Evidera. KVB, employee and shareholder of Galapagos NV., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Lower-limb running injuries are common. Running shoes have been proposed as one means of reducing injury risk. However, there is uncertainty as to how effective running shoes are for the prevention of injury. It is also unclear how the effects of different characteristics of running shoes prevent injury., Objectives: To assess the effects (benefits and harms) of running shoes for preventing lower-limb running injuries in adult runners., Search Methods: We searched the following databases: CENTRAL, MEDLINE, Embase, AMED, CINAHL Plus and SPORTDiscus plus trial registers WHO ICTRP and ClinicalTrials.gov. We also searched additional sources for published and unpublished trials. The date of the search was June 2021., Selection Criteria: We included randomised controlled trials (RCTs) and quasi-RCTs involving runners or military personnel in basic training that either compared a) a running shoe with a non-running shoe; b) different types of running shoes (minimalist, neutral/cushioned, motion control, stability, soft midsole, hard midsole); or c) footwear recommended and selected on foot posture versus footwear not recommended and not selected on foot posture for preventing lower-limb running injuries. Our primary outcomes were number of people sustaining a lower-limb running injury and number of lower-limb running injuries. Our secondary outcomes were number of runners who failed to return to running or their previous level of running, runner satisfaction with footwear, adverse events other than musculoskeletal injuries, and number of runners requiring hospital admission or surgery, or both, for musculoskeletal injury or adverse event., Data Collection and Analysis: Two review authors independently assessed study eligibility and performed data extraction and risk of bias assessment. The certainty of the included evidence was assessed using GRADE methodology., Main Results: We included 12 trials in the analysis which included a total of 11,240 participants, in trials that lasted from 6 to 26 weeks and were carried out in North America, Europe, Australia and South Africa. Most of the evidence was low or very low certainty as it was not possible to blind runners to their allocated running shoe, there was variation in the definition of an injury and characteristics of footwear, and there were too few studies for most comparisons. We did not find any trials that compared running shoes with non-running shoes. Neutral/cushioned versus minimalist (5 studies, 766 participants) Neutral/cushioned shoes may make little or no difference to the number of runners sustaining a lower-limb running injuries when compared with minimalist shoes (low-certainty evidence) (risk ratio (RR) 0.77, 95% confidence interval (CI) 0.59 to 1.01). One trial reported that 67% and 92% of runners were satisfied with their neutral/cushioned or minimalist running shoes, respectively (RR 0.73, 95% CI 0.47 to 1.12). Another trial reported mean satisfaction scores ranged from 4.0 to 4.3 in the neutral/ cushioned group and 3.6 to 3.9 in the minimalist running shoe group out of a total of 5. Hence neutral/cushioned running shoes may make little or no difference to runner satisfaction with footwear (low-certainty evidence). Motion control versus neutral / cushioned (2 studies, 421 participants) It is uncertain whether or not motion control shoes reduce the number of runners sustaining a lower-limb running injuries when compared with neutral / cushioned shoes because the quality of the evidence has been assessed as very low certainty (RR 0.92, 95% CI 0.30 to 2.81). Soft midsole versus hard midsole (2 studies, 1095 participants) Soft midsole shoes may make little or no difference to the number of runners sustaining a lower-limb running injuries when compared with hard midsole shoes (low-certainty of evidence) (RR 0.82, 95% CI 0.61 to 1.10). Stability versus neutral / cushioned (1 study, 57 participants) It is uncertain whether or not stability shoes reduce the number of runners sustaining a lower-limb running injuries when compared with neutral/cushioned shoes because the quality of the evidence has been assessed as very low certainty (RR 0.49, 95% CI 0.18 to 1.31). Motion control versus stability (1 study, 56 participants) It is uncertain whether or not motion control shoes reduce the number of runners sustaining a lower-limb running injuries when compared with stability shoes because the quality of the evidence has been assessed as very low certainty (RR 3.47, 95% CI 1.43 to 8.40). Running shoes prescribed and selected on foot posture (3 studies, 7203 participants) There was no evidence that running shoes prescribed based on static foot posture reduced the number of injuries compared with those who received a shoe not prescribed based on foot posture in military recruits (Rate Ratio 1.03, 95% CI 0.94 to 1.13). Subgroup analysis confirmed these findings were consistent between males and females. Therefore, prescribing running shoes and selecting on foot posture probably makes little or no difference to lower-limb running injuries (moderate-certainty evidence). Data were not available for all other review outcomes., Authors' Conclusions: Most evidence demonstrates no reduction in lower-limb running injuries in adults when comparing different types of running shoes. Overall, the certainty of the evidence determining whether different types of running shoes influence running injury rates was very low to low, and as such we are uncertain as to the true effects of different types of running shoes upon injury rates. There is no evidence that prescribing footwear based on foot type reduces running-related lower-limb injures in adults. The evidence for this comparison was rated as moderate and as such we can have more certainty when interpreting these findings. However, all three trials included in this comparison used military populations and as such the findings may differ in recreational runners.  Future researchers should develop a consensus definition of running shoe design to help standardise classification. The definition of a running injury should also be used consistently and confirmed via health practitioners. More researchers should consider a RCT design to increase the evidence in this area. Lastly, future work should look to explore the influence of different types or running shoes upon injury rates in specific subgroups., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Humid coastal dune slacks are an endangered habitat in Northwestern Europe. In the UK, dune slacks are currently classified as being in 'unfavourable' condition, with projected decrease in England of up to 30% by 2036. Studies in mainland Europe suggest that regional factors (e.g. slack area, age, and isolation) are more important than local factors (e.g. soil, pH, soil nutrient and water status) in driving successional vegetation processes in coastal slacks. However, this has never been tested for the UK, where approximately 14% of European slacks occur. We used previously established survey protocols to test whether regional factors are more important than local factors in UK coastal slacks, along the Sefton Coast in NW England. We found that slack area and slack age were more important than local factors in driving plant community composition and species richness. We also showed that higher levels of management, such as active grazing and invasive shrub and tree removal, are effective in increasing soil moisture levels in slacks. Our results suggest that similar successional processes are likely to be important in slacks in the NW of England, compared to mainland Europe., Competing Interests: The authors have declared that no competing interests exist.

Background: Although targeted biological treatments have transformed the outlook for patients with rheumatoid arthritis, 40% of patients show poor clinical response, which is mechanistically still unexplained. Because more than 50% of patients with rheumatoid arthritis have low or absent CD20 B cells-the target for rituximab-in the main disease tissue (joint synovium), we hypothesised that, in these patients, the IL-6 receptor inhibitor tocilizumab would be more effective. The aim of this trial was to compare the effect of tocilizumab with rituximab in patients with rheumatoid arthritis who had an inadequate response to anti-tumour necrosis factor (TNF) stratified for synovial B-cell status., Methods: This study was a 48-week, biopsy-driven, multicentre, open-label, phase 4 randomised controlled trial (rituximab vs tocilizumab in anti-TNF inadequate responder patients with rheumatoid arthritis; R4RA) done in 19 centres across five European countries (the UK, Belgium, Italy, Portugal, and Spain). Patients aged 18 years or older who fulfilled the 2010 American College of Rheumatology and European League Against Rheumatism classification criteria for rheumatoid arthritis and were eligible for treatment with rituximab therapy according to UK National Institute for Health and Care Excellence guidelines were eligible for inclusion in the trial. To inform balanced stratification, following a baseline synovial biopsy, patients were classified histologically as B-cell poor or rich. Patients were then randomly assigned (1:1) centrally in block sizes of six and four to receive two 1000 mg rituximab infusions at an interval of 2 weeks (rituximab group) or 8 mg/kg tocilizumab infusions at 4-week intervals (tocilizumab group). To enhance the accuracy of the stratification of B-cell poor and B-cell rich patients, baseline synovial biopsies from all participants were subjected to RNA sequencing and reclassified by B-cell molecular signature. The study was powered to test the superiority of tocilizumab over rituximab in the B-cell poor population at 16 weeks. The primary endpoint was defined as a 50% improvement in Clinical Disease Activity Index (CDAI50%) from baseline. The trial is registered on the ISRCTN database, ISRCTN97443826, and EudraCT, 2012-002535-28., Findings: Between Feb 28, 2013, and Jan 17, 2019, 164 patients were classified histologically and were randomly assigned to the rituximab group (83 [51%]) or the tocilizumab group (81 [49%]). In patients histologically classified as B-cell poor, there was no statistically significant difference in CDAI50% between the rituximab group (17 [45%] of 38 patients) and the tocilizumab group (23 [56%] of 41 patients; difference 11% [95% CI -11 to 33], p=0·31). However, in the synovial biopsies classified as B-cell poor with RNA sequencing the tocilizumab group had a significantly higher response rate compared with the rituximab group for CDAI50% (rituximab group 12 [36%] of 33 patients vs tocilizumab group 20 [63%] of 32 patients; difference 26% [2 to 50], p=0·035). Occurrence of adverse events (rituximab group 76 [70%] of 108 patients vs tocilizumab group 94 [80%] of 117 patients; difference 10% [-1 to 21) and serious adverse events (rituximab group 8 [7%] of 108 vs tocilizumab group 12 [10%] of 117; difference 3% [-5 to 10]) were not significantly different between treatment groups., Interpretation: The results suggest that RNA sequencing-based stratification of rheumatoid arthritis synovial tissue showed stronger associations with clinical responses compared with histopathological classification. Additionally, for patients with low or absent B-cell lineage expression signature in synovial tissue tocilizumab is more effective than rituximab. Replication of the results and validation of the RNA sequencing-based classification in independent cohorts is required before making treatment recommendations for clinical practice., Funding: Efficacy and Mechanism Evaluation programme from the UK National Institute for Health Research., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Large areas of naturally open peatland in western Europe were drained and planted with non-native conifers in the twentieth century. Efforts are currently underway to restore many of these sites. Ultimately, forest-to-bog restoration aims to bring back functional peatlands that can sequester carbon but there is a lack of empirical evidence for whether current approaches are effective. Using a chronosequence design, we compared the annual gaseous carbon balance of two forest-to-bog restoration areas with an open area not subject to afforestation. A closed chamber method was used to determine gas fluxes (Net Ecosystem Respiration, Gross Primary Productivity, Net Ecosystem Exchange (NEE) and methane (CH 4 )) over a twelve-month period for locations spanning the range of peatland microtopography and vegetation communities. Relationships between gas fluxes, vegetation/cover and environmental factors were analysed and regression models used to estimate annual CO 2 and CH 4 budgets. During the study period, NEE estimates (total gaseous C expressed as CO 2 -eq) showed a net sink for the unafforested (-102 g C m - 2  yr - 1 ) and oldest (-131 g C m - 2  yr - 1 ) restoration area (17 years post-restoration 'RES 17 YRS'), whilst the youngest restoration area (6 years post-restoration 'RES 6YRS'), was a net source (35 g C m - 2  yr - 1 ). We observed significantly higher CH 4 emissions from restoration areas dominated by Eriophorum angustifolium compared with other peatland vegetation types. Sampling points with higher cover of Sphagnum were found to be most effective for C sequestration. Overall, vegetation composition/cover was observed to be an important factor determining C emissions from forest-to-bog restoration areas. These results suggest that restoration is effective in returning the carbon sink function of peatlands damaged by commercial forestry and - depending on restoration techniques - timescales of >10 years may be required., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aim: To investigate persons with dementia and their informal caregivers' views of inter-sectoral information, communication and collaboration throughout the trajectory of dementia care, in eight European countries., Background: Living with dementia and being next of kin to a person with dementia means having to live through stages that have different characteristics, needs, challenges and requirements., Design: Qualitative research. Focus groups were conducted in England, Estonia, Finland, France, Germany, The Netherlands, Spain and Sweden., Methods: Persons with dementia and their informal caregivers (N = 137) participated in focus group interviews during 2011. Content analysis generated a tentative model of information, communication and collaboration for people with dementia and their caregivers, which was then tested., Results: The core finding was that information, communication and collaboration were to be focused on the persons with dementia and the informal caregivers. Entering into the trajectory of the disease and its consequences was addressed as an important point of departure. The relation to professional care required establishing a trusting relationship, tailor-made intervention and a single person or organization to contact. Professional knowledge and commitment, variation in service and care adapted to needs were important., Conclusion: As focus of care is on the person with dementia and their informal caregivers, a dyadic approach seems most suitable for dementia care. A trusting relationship and a specific person or organization to contact seem to be indicators of best practice, as does adaptation to the needs of the person with dementia and their informal caregiver., (© 2014 John Wiley & Sons Ltd.)