Flexor Injury Rehabilitation Splint Trial (FIRST): protocol for a pragmatic randomised controlled trial comparing three splints for finger flexor tendon repairs.

BACKGROUND: Without surgical repair, flexor tendon injuries do not heal and patients' ability to bend fingers and grip objects is impaired. However, flexor tendon repair surgery also requires optimal rehabilitation. There are currently three custom-made splints used in the rehabilitation of zone I/II flexor tendon repairs, each with different assumed harm/benefit profiles: the dorsal forearm and hand-based splint (long), the Manchester short splint (short), and the relative motion flexion splint (mini). There is, however, no robust evidence as to which splint, if any, is most clinical or cost effective. The Flexor Injury Rehabilitation Splint Trial (FIRST) was designed to address this evidence gap. METHODS: FIRST is a parallel group, superiority, analyst-blind, multi-centre, individual participant-randomised controlled trial. Participants will be assigned 1:1:1 to receive either the long, short, or mini splint. We aim to recruit 429 participants undergoing rehabilitation following zone I/II flexor tendon repair surgery. Potential participants will initially be identified prior to surgery, in NHS hand clinics across the UK, and consented and randomised at their splint fitting appointment post-surgery. The primary outcome will be the mean post-randomisation score on the patient-reported wrist and hand evaluation measure (PRWHE), assessed at 6, 12, 26, and 52 weeks post randomisation. Secondary outcome measures include blinded grip strength and active range of movement (AROM) assessments, adverse events, adherence to the splinting protocol (measured via temperature sensors inserted into the splints), quality of life assessment, and further patient-reported outcomes. An economic evaluation will assess the cost-effectiveness of each splint, and a qualitative sub-study will evaluate participants' preferences for, and experiences of wearing, the splints. Furthermore, a mediation analysis will determine the relationship between patient preferences, splint adherence, and splint effectiveness. DISCUSSION: FIRST will compare the three splints with respect to clinical efficacy, complications, quality of life and cost-effectiveness. FIRST is a pragmatic trial which will recruit from 26 NHS sites to allow findings to be generalisable to current clinical practice in the UK. It will also provide significant insights into patient experiences of splint wear and how adherence to splinting may impact outcomes. TRIAL REGISTRATION: ISRCTN: 10236011.

Personalised versus standard text message prompts for increasing trial participant response to telephone follow-up: an embedded randomised controlled retention trial.

BACKGROUND: Improving retention within randomised controlled trials is important. The effectiveness of different strategies can be assessed using a Study Within A Trial (SWAT). Previous research has shown personalised text message reminders improve clinic attendance rates; however, the results are mixed on improving postal questionnaire return. This SWAT aims to assess whether personalised text message reminders improve completion rates for scheduled telephone follow-ups. METHODS: This SWAT is a two-arm, multi-centre randomised controlled trial with equal allocation. The host trial was the Melatonin for Anxiety prior to General anaesthesia In Children trial (ISRCTN 18296119), where the child's caregiver was to answer a scheduled telephone follow-up 14 days post-surgery; participants for the SWAT were therefore the caregiver. Text messages were sent 24-48 h before the scheduled call and the personalised version contained the first name of the caregiver which was omitted in the non-personalised version. The primary outcome was questionnaire completion rate, defined as the proportion of caregivers successfully contacted, and completed any of the questionnaires, over the telephone within the follow-up window (day 14 + 7 days). RESULTS: The SWAT included 100 of the 110 (91%) participants randomised into the host trial. Randomisation within the SWAT was equal between non-personalised (n = 50) and personalised (n = 50) interventions. The overall questionnaire response rate was 73% with a difference between the two interventions of 68% in the non-personalised text message arm and 78% in the personalised text message arm. The adjusted absolute risk difference was 7.1% (95% confidence interval = -10.2%, 24.4%). There was no difference in either the time to response or the number of contact attempts between the two interventions. CONCLUSIONS: There is some evidence that personalised text messages could be effective at increasing response rates when data is collected via telephone and in a population of caregivers for paediatric trial participants. However, similar SWATs have shown mixed results. Given the low-cost and low risks associated with personalising text message reminders, this SWAT could be implemented easily in other RCTs scheduling telephone follow-up appointments. TRIAL REGISTRATION: ISRCTN 18296119 , SWAT 35 (MRC Northern Ireland Network for Trials Methodology Network).

Safety and efficacy of autologous haematopoietic stem-cell transplantation with low-dose cyclophosphamide mobilisation and reduced intensity conditioning versus standard of care in refractory Crohn's disease (ASTIClite): an open-label, multicentre, randomised controlled trial.

BACKGROUND: A previous controlled trial of autologous haematopoietic stem-cell transplantation (HSCT) in patients with refractory Crohn's disease did not meet its primary endpoint and reported high toxicity. We aimed to assess the safety and efficacy of HSCT with an immune-ablative regimen of reduced intensity versus standard of care in this patient population. METHODS: This open-label, multicentre, randomised controlled trial was conducted in nine National Health Service hospital trusts across the UK. Adults (aged 18-60 years) with active Crohn's disease on endoscopy (Simplified Endoscopic Score for Crohn's Disease [SES-CD] ulcer sub-score of ≥2) refractory to two or more classes of biological therapy, with no perianal or intra-abdominal sepsis or clinically significant comorbidity, were recruited. Participants were centrally randomly assigned (2:1) to either HSCT with a reduced dose of cyclophosphamide (intervention group) or standard care (control group). Randomisation was stratified by trial site by use of random permuted blocks of size 3 and 6. Patients in the intervention group underwent stem-cell mobilisation (cyclophosphamide 1 g/m2 with granulocyte colony-stimulating factor (G-CSF) 5 µg/kg) and stem-cell harvest (minimum 2·0 × 106 CD34+ cells per kg), before conditioning (fludarabine 125 mg/m2, cyclophosphamide 120 mg/kg, and rabbit anti-thymocyte globulin [thymoglobulin] 7·5 mg/kg in total) and subsequent stem-cell reinfusion supported by G-CSF. Patients in the control group continued any available conventional, biological, or nutritional therapy. The primary outcome was absence of endoscopic ulceration (SES-CD ulcer sub-score of 0) without surgery or death at week 48, analysed in the intention-to-treat population by central reading. This trial is registered with the ISRCTN registry, 17160440. FINDINGS: Between Oct 18, 2018, and Nov 8, 2019, 49 patients were screened for eligibility, of whom 23 (47%) were randomly assigned: 13 (57%) to the intervention group and ten (43%) to the control group. In the intervention group, ten (77%) participants underwent HSCT and nine (69%) reached 48-week follow-up; in the control group, nine (90%) reached 48-week follow-up. The trial was halted in response to nine reported suspected unexpected serious adverse reactions in six (46%) patients in the intervention group, including renal failure due to proven thrombotic microangiopathy in three participants and one death due to pulmonary veno-occlusive disease. At week 48, absence of endoscopic ulceration without surgery or death was reported in three (43%) of seven participants in the intervention group and in none of six participants in the control group with available data. Serious adverse events were more frequent in the intervention group (38 in 13 [100%] patients) than in the control group (16 in four [40%] patients). A second patient in the intervention group died after week 48 of respiratory and renal failure. INTERPRETATION: Although HSCT with an immune-ablative regimen of reduced intensity decreased endoscopic disease activity, significant adverse events deem this regimen unsuitable for future clinical use in patients with refractory Crohn's disease. FUNDING: Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research partnership.

The association between long-term conditions and uptake of population-based screening for colorectal cancer: results from two English cohort studies.

INTRODUCTION: Uptake of screening for colorectal cancer (CRC) can reduce mortality, and population-based screening is offered in England. To date, there is little evidence on the association between having a long-term condition (LTC) and CRC screening uptake. The objective of this study was to examine the association between having an LTC and uptake of CRC screening in England with the guaiac fecal occult blood test, with a particular focus on common mental disorders. METHODS: The study was a preregistered secondary analysis of two cohorts: first, a linked data set between the regional Yorkshire Health Study (YHS) and the National Health Service National Bowel Cancer Screening Program (BCSP, years 2006-2014); second, the national English Longitudinal Study of Ageing (ELSA, years 2014-2015). Individuals eligible for BCSP screening who participated in either the YHS (7,142) or ELSA Wave 7 (4,099) were included. Study registration: ClinicalTrials.gov, number NCT02503969. RESULTS: In both the cohorts, diabetes was associated with lower uptake (YHS odds ratio [OR] for non-uptake 1.35, 95% CI 1.03-1.78; ELSA 1.33, 1.03-1.72) and osteoarthritis was associated with increased uptake (YHS 0.75, 0.57-0.99; ELSA 0.76, 0.62-0.93). After controlling for broader determinants of health, there was no evidence of significantly different uptake for individuals with common mental disorders. CONCLUSION: Two large independent cohorts provided evidence that uptake of CRC screening is lower among individuals with diabetes and higher among individuals with osteoarthritis. Further work should compare barriers and facilitators to screening among individuals with either of these conditions. This study also demonstrates the benefits of data linkage for improving clinical decision-making.

PLEASANT: Preventing and Lessening Exacerbations of Asthma in School-age children Associated with a New Term - a cluster randomised controlled trial and economic evaluation.

BACKGROUND: Asthma episodes and deaths are known to be seasonal. A number of reports have shown peaks in asthma episodes in school-aged children associated with the return to school following the summer vacation. A fall in prescription collection in the month of August has been observed, and was associated with an increase in the number of unscheduled contacts after the return to school in September. OBJECTIVE: The primary objective of the study was to assess whether or not a NHS-delivered public health intervention reduces the September peak in unscheduled medical contacts. DESIGN: Cluster randomised trial, with the unit of randomisation being 142 NHS general practices, and trial-based economic evaluation. SETTING: Primary care. INTERVENTION: A letter sent (n = 70 practices) in July from their general practitioner (GP) to parents/carers of school-aged children with asthma to remind them of the importance of taking their medication, and to ensure that they have sufficient medication prior to the start of the new school year in September. The control group received usual care. MAIN OUTCOME MEASURES: The primary outcome measure was the proportion of children aged 5-16 years who had an unscheduled medical contact in September 2013. Supporting end points included the proportion of children who collected prescriptions in August 2013 and unscheduled contacts through the following 12 months. Economic end points were quality-adjusted life-years (QALYs) gained and costs from an NHS and Personal Social Services perspective. RESULTS: There is no evidence of effect in terms of unscheduled contacts in September. Among children aged 5-16 years, the odds ratio (OR) was 1.09 [95% confidence interval (CI) 0.96 to 1.25] against the intervention. The intervention did increase the proportion of children collecting a prescription in August (OR 1.43, 95% CI 1.24 to 1.64) as well as scheduled contacts in the same month (OR 1.13, 95% CI 0.84 to 1.52). For the wider time intervals (September-December 2013 and September-August 2014), there is weak evidence of the intervention reducing unscheduled contacts. The intervention did not reduce unscheduled care in September, although it succeeded in increasing the proportion of children collecting prescriptions in August as well as having scheduled contacts in the same month. These unscheduled contacts in September could be a result of the intervention, as GPs may have wanted to see patients before issuing a prescription. The economic analysis estimated a high probability that the intervention was cost-saving, for baseline-adjusted costs, across both base-case and sensitivity analyses. There was no increase in QALYs. LIMITATION: The use of routine data led to uncertainty in the coding of medical contacts. The uncertainty was mitigated by advice from a GP adjudication panel. CONCLUSIONS: The intervention did not reduce unscheduled care in September, although it succeeded in increasing the proportion of children both collecting prescriptions and having scheduled contacts in August. After September there is weak evidence in favour of the intervention. The intervention had a favourable impact on costs but did not demonstrate any impact on QALYs. The results of the trial indicate that further work is required on assessing and understanding adherence, both in terms of using routine data to make quantitative assessments, and through additional qualitative interviews with key stakeholders such as practice nurses, GPs and a wider group of children with asthma. TRIAL REGISTRATION: Current Controlled Trials ISRCTN03000938. FUNDING DETAILS: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 93. See the HTA programme website for further project information.