Gait Rehabilitation for Foot and Ankle Impairments in Early Rheumatoid Arthritis: a Feasibility Study of a New Gait Rehabilitation Programme (GREAT Strides)

BackgroundFoot impairments in early rheumatoid arthritis are common and lead to progressive deterioration of lower limb function. A gait rehabilitation programme underpinned by psychological techniques to improve adherence, may preserve gait and lower limb function. This study evaluated the feasibility of a novel gait rehabilitation intervention (GREAT Strides) and a future trial. MethodsThis was a mixed methods feasibility study with embedded qualitative components. People with early (<2 years) rheumatoid arthritis (RA) and foot pain were eligible. Intervention acceptability was evaluated using a questionnaire. Adherence was evaluated using the Exercise Adherence Rating Scale (EARS). Safety was monitored using case report forms. Participants and therapists were interviewed to explore intervention acceptability. Deductive thematic analysis was applied using the Theoretical Framework of Acceptability. For fidelity, audio recordings of interventions sessions were assessed using the Motivational Interviewing Treatment Integrity (MITI) scale. Measurement properties of four candidate primary outcomes, rates of recruitment, attrition and data completeness were evaluated.Results35 participants (68.6% female) with median age (inter-quartile range [IQR]) 60.1 [49.4-68.4] years and disease duration 9.1 [4.0-16.2] months), were recruited and 23 (65.7%) completed 12-week follow-up. Intervention acceptability was excellent; 21/23 were confident that it could help and would recommend it; 22/23 indicated it made sense to them. Adherence was good, with a median [IQR] EARS score of 17/24 [12.5-22.5]. One serious adverse event that was unrelated to the study was reported. Twelve participants’ and 9 therapists’ interviews confirmed intervention acceptability, identified perceptions of benefit, but also highlighted some barriers to completion. Mean MITI scores for relational (4.38) and technical (4.19) aspects of motivational interviewing demonstrate good fidelity. The Foot Function Index disability subscale performed best in terms of theoretical consistency and was deemed most practical. ConclusionGREAT Strides was viewed as acceptable by patients and therapists, and we observed high intervention fidelity, good patient adherence and no safety concerns. A future trial to test the additional benefit of GREAT Strides to usual care will benefit from amended eligibility criteria, refinement of the intervention and strategies to ensure higher follow-up rates. The Foot Function Index disability subscale was identified as the primary outcome.Trial registrationISRCTN14277030

Early Positive Approaches to Support (E-PAtS) for Families of Young Children With Intellectual Disability: A Feasibility Randomised Controlled Trial

Background: Parents of children with intellectual disabilities are likely to experience poorer mental well-being and face challenges accessing support. Early Positive Approaches to Support (E-PAtS) is a group-based programme, co-produced with parents and professionals, based on existing research evidence and a developmental systems approach to support parental mental well-being. The aim of this study was to assess the feasibility of community service provider organisations delivering E-PAtS to parents/family caregivers of young children with intellectual disability, to inform a potential definitive randomised controlled trial of the effectiveness and cost-effectiveness of E-PAtS.Methods: This study was a feasibility cluster randomised controlled trial, with embedded process evaluation. Up to two parents/family caregivers of a child (18 months to &lt;6 years old) with intellectual disability were recruited at research sites and allocated to intervention (E-PAtS and usual practise) or control (usual practise) on a 1:1 basis at cluster (family) level. Data were collected at baseline and 3 and 12 months' post-randomisation. The following feasibility outcomes were assessed: participant recruitment rates and effectiveness of recruitment pathways; retention rates; intervention adherence and fidelity; service provider recruitment rates and willingness to participate in a future trial; barriers and facilitating factors for recruitment, engagement, and intervention delivery; and feasibility of collecting outcome measures.Results: Seventy-four families were randomised to intervention or control (n = 37). Retention rates were 72% at 12 months post-randomisation, and completion of the proposed primary outcome measure (WEMWBS) was 51%. Recruitment of service provider organisations and facilitators was feasible and intervention implementation acceptable. Adherence to the intervention was 76% and the intervention was well-received by participants; exploratory analyses suggest that adherence and attendance may be associated with improved well-being. Health economic outcome measures were collected successfully and evidence indicates that linkage with routine data would be feasible in a future trial.Conclusions: The E-PAtS Feasibility RCT has demonstrated that the research design and methods of intervention implementation are generally feasible. Consideration of the limitations of this feasibility trial and any barriers to conducting a future definitive trial, do however, need to be considered by researchers.Clinical Trial Registration:https://www.isrctn.com, identifier: ISRCTN70419473.

The Role and Impact of Minimal Residual Disease in NSCLC

Purpose of Review There has been a huge development in the assessment of malignancies through liquid biopsies last years, especially for NSCLC, where its use has become part of clinical practice in some settings. We aim to summarize current evidence about minimal residual disease and its use in lung cancer. Recent Findings Recent studies using ctDNA in NSCLC but also in other types of cancer found strong correlations between the presence of ctDNA and the risk of disease progression or death after curative intent, despite current technical difficulties in performing this analysis (high sensitivity and specificity required). Summary Evaluation of MRD in NSCLC, especially through ctDNA, could be an important point in future trial designs and could permit a more “targeted” adjuvant treatment.

Feasibility and design of a trial regarding the optimal mode of delivery for preterm birth: the CASSAVA multiple methods study

Background Around 60,000 babies are born preterm (prior to 37 weeks’ gestation) each year in the UK. There is little evidence on the optimal birth mode (vaginal or caesarean section). Objective The overall aim of the CASSAVA project was to determine if a trial to define the optimal mode of preterm birth could be carried out and, if so, determine what sort of trial could be conducted and how it could best be performed. We aimed to determine the specific groups of preterm women and babies for whom there are uncertainties about the best planned mode of birth, and if there would be willingness to recruit to, and participate in, a randomised trial to address some, but not all, of these uncertainties. This project was conducted in response to a Heath Technology Assessment programme commissioning call (17/22 ‘Mode of delivery for preterm infants’). Methods We conducted clinician and patient surveys (n = 224 and n = 379, respectively) to identify current practice and opinion, and a consensus survey and Delphi workshop (n = 76 and n = 22 participants, respectively) to inform the design of a hypothetical clinical trial. The protocol for this clinical trial/vignette was used in telephone interviews with clinicians (n = 24) and in focus groups with potential participants (n = 13). Results Planned sample size and data saturation was achieved for all groups except for focus groups with participants, as this had to be curtailed because of the COVID-19 pandemic and data saturation was not achieved. There was broad agreement from parents and health-care professionals that a trial is needed. The clinician survey demonstrated a variety of practice and opinion. The parent survey suggested that women and their families generally preferred vaginal birth at later gestations and caesarean section for preterm infants. The interactive workshop and Delphi consensus process confirmed the need for more evidence (hence the case for a trial) and provided rich information on what a future trial should entail. It was agreed that any trial should address the areas with most uncertainty, including the management of women at 26–32 weeks’ gestation, with either spontaneous preterm labour (cephalic presentation) or where preterm birth was medically indicated. Clear themes around the challenges inherent in conducting any trial emerged, including the concept of equipoise itself. Specific issues were as follows: different clinicians and participants would be in equipoise for each clinical scenario, effective conduct of the trial would require appropriate resources and expertise within the hospital conducting the trial, potential participants would welcome information on the trial well before the onset of labour and minority ethnic groups would require tailored approaches. Conclusion Given the lack of evidence and the variation of practice and opinion in this area, and having listened to clinicians and potential participants, we conclude that a trial should be conducted and the outlined challenges resolved. Future work The CASSAVA project could be used to inform the design of a randomised trial and indicates how such a trial could be carried out. Any future trial would benefit from a pilot with qualitative input and a study within a trial to inform optimal recruitment. Limitations Certainty that a trial could be conducted can be determined only when it is attempted. Trial registration Current Controlled Trials ISRCTN12295730. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 61. See the NIHR Journals Library website for further project information.

Incorporating Missing Outcome Data in The Sample Size Calculation For a Future Trial: A Case Study Using a Single Trial, a Pairwise and Network Meta-Analysis

Background: To illustrate the advantages of using network meta-analysis (NMA) as compared to a trial or a pairwise meta-analysis to estimate the amount of missing outcome data (MOD) for a target comparison in order to adjust the required sample size for possible participant losses in a future trial.Methods: We introduced the concept of transitive risks to obtain the absolute risks of MOD for all interventions of the network. We used the network of a published systematic review on a binary outcome to apply the proposed concept and to calculate the required sample size in a future trial for a selected target comparison. For that comparison, we also calculated the required sample size using the corresponding trials separately, and after pooling these trials in a random-effects meta-analysis. Results: Ignoring MOD from the sample size calculation led to the smallest sample size. When either trial was considered, the risk of MOD ranged from 1% to 13% in the compared intervention arms, therefore, increasing the sample size from 1% to 12%. Performing a pairwise meta-analysis yielded a risk of MOD equal to 6% and 9% in the active and control arms, respectively, which inflated the sample size by 8%. Using NMA, the corresponding risks of MOD were 10% and 13%, which increased the sample size by 13%. Conclusions: Provided that the transitivity assumption holds, incorporating the absolute risks of MOD in the sample size calculation for a target comparison of the network led to better planning of a future trial.

Shifting Priorities: Are Attitudes Changing at the International Criminal Court about Trials in absentia?

A recent decision by the International Criminal Court’s Appeals Chamber in the Gbagbo and Blé Goudé case raised the possibility of a shift away from the long-standing practice of only holding trial in the presence of the accused. The final paragraphs of the 28 May 2020 decision asserts that any future trial proceedings in the Gbagbo et al. case could be held in the absence of the defendants should Mr Gbagbo and Mr Blé Goudé be released from custody and then later fail to appear for trial. This article examines the Appeals Chamber’s decision in light of the Court’s Statute, existing jurisprudence at the icc and within the larger context of international criminal law. It concludes that the Appeals Chamber’s decision fails to properly understand the right to be present at trial as it exists in the Rome Statute nor does it comply with any identified general principle of law.