SWATted away : the challenging experience of setting up a programme of SWATs in paediatric trials

The authors wish to acknowledge the National Institute of Health Research (NIHR) Health Services and Delivery Research funding for the TRECA study (NIHR Health Services and Delivery Research Project: 14/21/21). The NIHR did not have a role in the design of the study or the writing of this manuscript. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.Peer reviewedPublisher PD

Does digital, multimedia information increase recruitment and retention in a children’s wrist fracture treatment trial, and what do people think of it? A randomised controlled Study Within A Trial (SWAT)

Objectives To evaluate digital, multimedia information (MMI) for its effects on trial recruitment, retention, decisions about participation and acceptability by patients, compared with printed information. Design Study Within A Trial using random cluster allocation within the Forearm Fracture Recovery in Children Evaluation (FORCE) study. Setting Emergency departments in 23 UK hospitals. Participants 1409 children aged 4–16 years attending with a torus (buckle) fracture, and their parents/guardian. Children’s mean age was 9.2 years, 41.0% were female, 77.4% were ethnically White and 90.0% spoke English as a first language. Interventions Participants and their parents/guardian received trial information either via multimedia, including animated videos, talking head videos and text (revised for readability and age appropriateness when needed) on tablet computer (MMI group; n=681), or printed participant information sheet (PIS group; n=728). Outcome measures Primary outcome was recruitment rate to FORCE. Secondary outcomes were Decision Making Questionnaire (nine Likert items, analysed summatively and individually), three ‘free text’ questions (deriving subjective evaluations) and trial retention. Results MMI produced a small, not statistically significant increase in recruitment: 475 (69.8%) participants were recruited from the MMI group; 484 (66.5%) from the PIS group (OR=1.35; 95% CI 0.76 to 2.40, p=0.31). A total of 324 (23.0%) questionnaires were returned and analysed. There was no difference in total Decision-Making Questionnaire scores: adjusted mean difference 0.05 (95% CI −1.23 to 1.32, p=0.94). The MMI group was more likely to report the information ‘very easy’ to understand (89; 57.8% vs 67; 39.4%; Z=2.60, p=0.01) and identify information that was explained well (96; 62.3% vs 71; 41.8%). Almost all FORCE recruits were retained at the 6 weeks’ timepoint and there was no difference in retention rate between the information groups: MMI (473; 99.6%); PIS (481; 99.4%)

Developing a core outcome set for evaluating medication adherence interventions for adults prescribed long-term medication in primary care

Background: Approximately half of people prescribed medications do not take them as prescribed. There is a significant unmet need regarding the barriers to medication adherence not being addressed in primary care. There is no agreement on which outcomes should be measured and reported in trials of medication adherence interventions. Objective: To develop a core outcome set (COS) for trials of medication adherence interventions in primary care for adults prescribed medications for long-term health conditions. Methods: A list of potentially relevant outcomes from the literature was developed. Using a two-round Delphi survey of stakeholder groups representing patients and their carers; primary care staff; and academic researchers with an interest in medication adherence; each outcome was scored in terms of importance for determining the effectiveness of medication adherence interventions in primary care. This was followed by two consensus workshops, where importance, as well as feasibility and acceptability of measurement, were considered in order to finalise the COS. Results: One hundred and fifty people took part in Delphi Round 1 and 101 took part in Round 2. Eight people attended the workshops (four attendees per workshop). Seven outcomes were identified as most important, feasible and acceptable to collect in medication adherence trials: Health-related quality of life, number of doses taken, persistence with medicines, starting (initiating) a medicine, relevance of the medication adherence intervention for an individual, mortality, and adverse medicine events. Conclusions: This COS represents the minimum outcomes that should be collected and reported in all medication adherence trials undertaken in primary care. When developing and finalizing the COS, feasibility and acceptability of collection of outcomes has been considered. In addition to the COS, medication adherence trials can choose to include outcomes to suit their specific context such as the health condition associated with their medication adherence intervention

The import and export of organic nitrogen species at a Scottish ombrotrophic peatland

Dissolved organic nitrogen (DON) contributes significantly to the overall nitrogen budget, but is not routinely measured in precipitation or stream water. In order to investigate the contribution of DON to the deposition and export of N, precipitation, stream and soil water samples were collected from an ombrotrophic peatland and analysed for DON over a 2-year period. In wet-only deposition DON contributed up to 10 % of the total dissolved nitrogen (TDN) and was the most dominant fraction in soil water (99 %) and stream water (75 %). NH4 + was the most dominate form of N in precipitation, with NO3 - contributing the least to precipitation, soil water and stream water. Precipitation and stream DON were qualitatively analysed by a two-dimensional gas chromatograph coupled to a nitrogen chemiluminescence detector (GC × GC-NCD) after trapping onto C18 solid phase extraction (SPE) cartridges. Ten unique compounds were detected and five identified as pyrrole, benzonitrile, dodecylamine, N-nitrosodipropylamine and decylamine. Five compounds were present in both precipitation and stream samples: pyrrole, benzonitrile and three unidentified compounds. The SPE-extraction efficiency for DON was very low (11 %), but with improvements DON speciation could become a valuable tool to provide information on its sources and pathways and inform chemical transport models

Patient and public involvement in a study of multimedia clinical trial information for children, young people and families

© 2020 Sheridan, Preston, Stones, Ainsworth, Taylor, Challinor, Ainsworth, Martin-Kerry, Brady and Knapp. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC BY) 4.0. https://creativecommons.org/licenses/by/4.0/.There is increasing recognition of the need to involve the public in health research, but accounts of how best to achieve this are scarce. This article describes public involvement in the TRials Engagement in Children and Adolescents (TRECA) study, which is developing and evaluating multimedia information resources to inform children, young people and their familes about clinical trials. A dedicated group of young people with long-term health conditions and their parents met regularly throughout the study; further involvement was sought when specific input was required. Review of formal impact records and informal discussions highlighted how public involvement can positively influence research practice and the people involved. By detailing the methods of involvement used, this work also provides guidance for successfully implementing public involvement in research, and highlights challenges that should be considered in future research projects.Peer reviewe

Supportive use of digital technologies during transition to adult healthcare for young people with long-term conditions, focusing on Type 1 diabetes mellitus: A scoping review.

Type 1 diabetes mellitus (T1DM) is the second most common chronic or long-term condition (LTC) affecting young people (YP); when transitioning from paediatric to adult healthcare, young people with LTCs such as T1DM are expected to self-manage medication, diet and clinical appointments. This scoping review aimed to analyse research examining ways digital health technologies were used to support YP with LTCs during transition from paediatric to adult healthcare and to establish YP's needs, experiences and challenges when transitioning. We aimed to identify knowledge gaps and inform development of a novel chatbot with components such as avatars and linked videos to help YP with T1DM gain self-management confidence and competence during transition. Nineteen studies identified through searching five electronic databases were included in this review. A combination of digital health technologies was used to support transition of YP with LTCs to adult healthcare. Barriers to successful transition were reported and YP described the importance of social relationships and transition readiness and expressed the need for individualised interventions that acknowledge social factors such as work and college. No supportive chatbots with components to help YP with T1DM were identified. This contribution will inform future development and evaluation of such a chatbot

Lack of Marburg virus transmission from experimentally infected to susceptible in-contact Egyptian fruit bats

Egyptian fruit bats (Rousettus aegyptiacus) were inoculated subcutaneously (n = 22) with Marburg virus (MARV). No deaths, overt signs of morbidity, or gross lesions was identified, but microscopic pathological changes were seen in the liver of infected bats. The virus was detected in 15 different tissues and plasma but only sporadically in mucosal swab samples, urine, and fecal samples. Neither seroconversion nor viremia could be demonstrated in any of the in-contact susceptible bats (n = 14) up to 42 days after exposure to infected bats. In bats rechallenged (n = 4) on day 48 after infection, there was no viremia, and the virus could not be isolated from any of the tissues tested. This study confirmed that infection profiles are consistent with MARV replication in a reservoir host but failed to demonstrate MARV transmission through direct physical contact or indirectly via air. Bats develop strong protective immunity after infection with MARV.This work was supported by the National Institute for Communicable Diseases.http://jid.oxfordjournals.orgam2016Paraclinical Science

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Oral Abstracts 7: RA ClinicalO37. Long-Term Outcomes of Early RA Patients Initiated with Adalimumab Plus Methotrexate Compared with Methotrexate Alone Following a Targeted Treatment Approach

Background: This analysis assessed, on a group level, whether there is a long-term advantage for early RA patients treated with adalimumab (ADA) + MTX vs those initially treated with placebo (PBO) + MTX who either responded to therapy or added ADA following inadequate response (IR). Methods: OPTIMA was a 78- week, randomized, controlled trial of ADA + MTX vs PBO + MTX in MTX-naïve early (<1 year) RA patients. Therapy was adjusted at week 26: ADA + MTX-responders (R) who achieved DAS28 (CRP) <3.2 at weeks 22 and 26 (Period 1, P1) were re-randomized to withdraw or continue ADA and PBO + MTX-R continued randomized therapy for 52 weeks (P2); IR-patients received open-label (OL) ADA + MTX during P2. This post hoc analysis evaluated the proportion of patients at week 78 with DAS28 (CRP) <3.2, HAQ-DI <0.5, and/or ΔmTSS ≤0.5 by initial treatment. To account for patients who withdrew ADA during P2, an equivalent proportion of R was imputed from ADA + MTX-R patients. Results: At week 26, significantly more patients had low disease activity, normal function, and/or no radiographic progression with ADA + MTX vs PBO + MTX (Table 1). Differences in clinical and functional outcomes disappeared following additional treatment, when PBO + MTX-IR (n = 348/460) switched to OL ADA + MTX. Addition of OL ADA slowed radiographic progression, but more patients who received ADA + MTX from baseline had no radiographic progression at week 78 than patients who received initial PBO + MTX. Conclusions: Early RA patients treated with PBO + MTX achieved comparable long-term clinical and functional outcomes on a group level as those who began ADA + MTX, but only when therapy was optimized by the addition of ADA in PBO + MTX-IR. Still, ADA + MTX therapy conferred a radiographic benefit although the difference did not appear to translate to an additional functional benefit. Disclosures: P.E., AbbVie, Merck, Pfizer, UCB, Roche, BMS—Provided Expert Advice, Undertaken Trials, AbbVie—AbbVie sponsored the study, contributed to its design, and participated in the collection, analysis, and interpretation of the data, and in the writing, reviewing, and approval of the final version. R.F., AbbVie, Pfizer, Merck, Roche, UCB, Celgene, Amgen, AstraZeneca, BMS, Janssen, Lilly, Novartis—Research Grants, Consultation Fees. S.F., AbbVie—Employee, Stocks. A.K., AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, UCB—Research Grants, Consultation Fees. H.K., AbbVie—Employee, Stocks. S.R., AbbVie—Employee, Stocks. J.S., AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, GlaxoSmithKline, Lilly, Pfizer (Wyeth), MSD (Schering-Plough), Novo-Nordisk, Roche, Sandoz, UCB—Research Grants, Consultation Fees. R.V., AbbVie, BMS, GlaxoSmithKline, Human Genome Sciences, Merck, Pfizer, Roche, UCB Pharma—Consultation Fees, Research Support. Table 1.Week 78 clinical, functional, and radiographic outcomes in patients who received continued ADA + MTX vs those who continued PBO + MTX or added open-label ADA following an inadequate response ADA + MTX, n/N (%)a PBO + MTX, n/N (%)b Outcome Week 26 Week 52 Week 78 Week 26 Week 52 Week 78 DAS28 (CRP) <3.2 246/466 (53) 304/465 (65) 303/465 (65) 139/460 (30)*** 284/460 (62) 300/460 (65) HAQ-DI <0.5 211/466 (45) 220/466 (47) 224/466 (48) 150/460 (33)*** 203/460 (44) 208/460 (45) ΔmTSS ≤0.5 402/462 (87) 379/445 (86) 382/443 (86) 330/459 (72)*** 318/440 (72)*** 318/440 (72)*** DAS28 (CRP) <3.2 + ΔmTSS ≤0.5 216/462 (47) 260/443 (59) 266/443 (60) 112/459 (24)*** 196/440 (45) 211/440 (48)*** DAS28 (CRP) <3.2 + HAQ-DI <0.5 + ΔmTSS ≤0.5 146/462 (32) 168/443 (38) 174/443 (39) 82/459 (18)*** 120/440 (27)*** 135/440 (31)** aIncludes patients from the ADA Continuation (n = 105) and OL ADA Carry On (n = 259) arms, as well as the proportional equivalent number of responders from the ADA Withdrawal arm (n = 102). bIncludes patients from the MTX Continuation (n = 112) and Rescue ADA (n = 348) arms. Last observation carried forward: DAS28 (CRP) and HAQ-DI; Multiple imputations: ΔmTSS. ***P < 0.001 and **iP < 0.01, respectively, for differences between initial treatments from chi-squar