Randomised controlled trials ('trials') are susceptible to poor participant recruitment and retention. Studies Within A Trial are the strongest methods for testing the effectiveness of strategies to ...improve recruitment and retention. However, relatively few of these have been conducted.
PROMoting THE Use of Studies Within A Trial aimed to facilitate at least 25 Studies Within A Trial evaluating recruitment or retention strategies. We share our experience of delivering the PROMoting THE Use of Studies Within A Trial programme, and the lessons learnt for undertaking randomised Studies Within A Trial.
A network of 10 Clinical Trials Units and 1 primary care research centre committed to conducting randomised controlled Studies Within A Trial of recruitment and/or retention strategies was established. Promising recruitment and retention strategies were identified from various sources including Cochrane systematic reviews, the Study Within A Trial Repository, and existing prioritisation exercises, which were reviewed by patient and public members to create an initial priority list of seven recruitment and eight retention interventions. Host trial teams could apply for funding and receive support from the PROMoting THE Use of Studies Within A Trial team to undertake Studies Within A Trial. We also tested the feasibility of undertaking co-ordinated Studies Within A Trial, across multiple host trials simultaneously.
Clinical trials unit-based trials recruiting or following up participants in any setting in the United Kingdom were eligible.
Clinical trials unit-based teams undertaking trials in any clinical context in the United Kingdom.
Funding of up to £5000 and support from the PROMoting THE Use of Studies Within A Trial team to design, implement and report Studies Within A Trial.
Number of host trials funded.
Forty-two Studies Within A Trial were funded (31 host trials), across 12 Clinical Trials Units. The mean cost of a Study Within A Trial was £3535. Twelve Studies Within A Trial tested the same strategy across multiple host trials using a co-ordinated Study Within A Trial design, and four used a factorial design. Two recruitment and five retention strategies were evaluated in more than one host trial. PROMoting THE Use of Studies Within A Trial will add 18% more Studies Within A Trial to the Cochrane systematic review of recruitment strategies, and 79% more Studies Within A Trial to the Cochrane review of retention strategies. For retention, we found that pre-notifying participants by card, letter or e-mail before sending questionnaires was effective, as was the use of pens, and sending personalised text messages to improve questionnaire response. We highlight key lessons learnt to guide others planning Studies Within A Trial, including involving patient and public involvement partners; prioritising and selecting strategies to evaluate and elements to consider when designing a Study Within A Trial; obtaining governance approvals; implementing Studies Within A Trial, including individual and co-ordinated Studies Within A Trials; and reporting Study Within A Trials.
The COVID-19 pandemic negatively impacted five Studies Within A Trial, being either delayed (
= 2) or prematurely terminated (
= 3).
PROMoting THE Use of Studies Within A Trial significantly increased the evidence base for recruitment and retention strategies. When provided with both funding and practical support, host trial teams successfully implemented Studies Within A Trial.
Future research should identify and target gaps in the evidence base, including widening Study Within A Trial uptake, undertaking more complex Studies Within A Trial and translating Study Within A Trial evidence into practice.
All Studies Within A Trial in the PROMoting THE Use of Studies Within A Trial programme had to be registered with the Northern Ireland Network for Trials Methodology Research Study Within A Trial Repository.
This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/55/80) and is published in full in
; Vol. 28, No. 2. See the NIHR Funding and Awards website for further award information.
Medical hydrogel applications have expanded rapidly over the past decade. Implantation in patients by noninvasive injection is preferred, but this requires hydrogel solidification from a low ...viscosity solution to occur in vivo via an applied stimuli. Transdermal photo-cross-linking of acrylated biopolymers with photoinitiators and lights offers a mild, spatiotemporally controlled solidification trigger. However, the current short wavelength initiators limit curing depth and efficacy because they do not absorb within the optical window of tissue (600–900 nm). As a solution to the current wavelength limitations, we report the development of a red light responsive initiator capable of polymerizing a range of acrylated monomers. Photoactivation occurs within a range of skin type models containing high biochromophore concentrations.
The onset of disability in bathing is particularly important for older adults as it can be rapidly followed by disability in other daily activities; this may represent a judicious time point for ...intervention in order to improve health, well-being and associated quality of life. An important environmental and preventative intervention is housing adaptation, but there are often lengthy waiting times for statutory provision. In this randomised controlled trial (RCT), we aim to evaluate the effectiveness and cost-effectiveness of bathing adaptations compared to no adaptations and to explore the factors associated with routine and expedited implementation of bathing adaptations.
BATH-OUT-2 is a multicentre, two-arm, parallel-group RCT. Adults aged 60 and over who are referred to their local authority for an accessible level access shower will be randomised, using pairwise randomisation, 1:1, to receive either an expedited provision of an accessible shower via the local authority or a usual care control waiting list. Participants will be followed up for a maximum of 12 months and will receive up to four follow-ups in this duration. The primary outcome will be the participant's physical well-being, assessed by the Physical Component Summary score of the Short Form-36 (SF-36), 4 weeks after the intervention group receives the accessible shower. The secondary outcomes include the Mental Component Summary score of the SF-36, self-reported falls, health and social care resource use, health-related quality of life (EQ-5D-5L), social care-related quality of life (Adult Social Care Outcomes Toolkit (ASCOT)), fear of falling (Short Falls Efficacy Scale), independence in bathing (Barthel Index bathing question), independence in daily activities (Barthel Index) and perceived difficulty in bathing (0-100 scale). A mixed-methods process evaluation will comprise interviews with stakeholders and a survey of local authorities with social care responsibilities in England.
The BATH-OUT-2 trial is designed so that the findings will inform future decisions regarding the provision of bathing adaptations for older adults. This trial has the potential to highlight, and then reduce, health inequalities associated with waiting times for bathing adaptations and to influence policies for older adults.
ISRCTN Registry ISRCTN48563324. Prospectively registered on 09/04/2021.
Lateral compression type1 (LC-1) fragility fractures are a common, painful injury in older adults resulting in reduced mobility. The incidence of these fractures is increasing with the growing older ...adult population. The current standard of care is non-surgical management; however, patients with this injury are at risk of long-term immobility and related complications. INFIX is a pelvic fixation device used in younger patients with high-energy fractures. The device is fitted via a percutaneous technique with no external pin sites and has good purchase even in osteoporotic bone. It therefore has the potential to be well tolerated in patients with LC-1 fragility fractures. INFIX could improve patients' ability to mobilise and reduce the risk of immobility-related complications. However, there is a risk of complications related to surgery, and robust evidence is required on patient outcomes. This study will investigate the clinical and cost-effectiveness of surgical fixation with INFIX compared to non-surgical management of LC-1 fragility fractures in older adults.
A multi-centre randomised controlled trial of 600 patients allocated 1:1 to non-surgical management or INFIX surgery. The study will have a 12-month internal pilot to assess recruitment and trial feasibility. The primary outcome will be the patient quality of life over 6 months, measured by the patient-reported EQ-5D-5L. The secondary outcomes will include physical function, mental health, pain, delirium, imaging assessment, resource use, and complications.
The L1FE study aims to compare the clinical and cost-effectiveness of surgical and non-surgical management of people aged 60 years and older with LC-1 fragility fractures. The trial is sufficiently powered and rigorously designed to inform future clinical and patient decision-making and allocation of NHS resources.
International Standard Randomised Controlled Trial Number Registry ISRCTN16478561. Registered on 8 April 2019.
Bone demonstrates good healing capacity, with a variety of strategies being utilized to enhance this healing. One potential strategy that has been suggested is the use of stem cells to accelerate ...healing.
The following databases were searched: MEDLINE, CENTRAL, EMBASE, Cochrane Database of Systematic Reviews, WHO-ICTRP, ClinicalTrials.gov, as well as reference checking of included studies. The inclusion criteria for the study were: population (any adults who have sustained a fracture, not including those with pre-existing bone defects); intervention (use of stem cells from any source in the fracture site by any mechanism); and control (fracture healing without the use of stem cells). Studies without a comparator were also included. The outcome was any reported outcomes. The study design was randomized controlled trials, non-randomized or observational studies, and case series.
In all, 94 eligible studies were identified. The clinical and methodological aspects of the studies were too heterogeneous for a meta-analysis to be undertaken. A narrative synthesis examined study characteristics, stem cell methods (source, aspiration, concentration, and application) and outcomes.
Insufficient high-quality evidence is available to determine the efficacy of stem cells for fracture healing. The studies were heterogeneous in population, methods, and outcomes. Work to address these issues and establish standards for future research should be undertaken.Cite this article:
2020;1-10:628-638.
How do language learners avoid the production of verb argument structure overgeneralization errors (
*The clown laughed the man
c.f.
The clown made the man laugh
), while retaining the ability to ...apply such generalizations productively when appropriate? This question has long been seen as one that is both particularly central to acquisition research and particularly challenging. Focussing on causative overgeneralization errors of this type, a previous study reported a computational model that learns, on the basis of corpus data and human-derived verb-semantic-feature ratings, to predict adults’ by-verb preferences for less- versus more-transparent causative forms (e.g., *
The clown laughed the man
vs
The clown made the man laugh
) across English, Hebrew, Hindi, Japanese and K’iche Mayan. Here, we tested the ability of this model (and an expanded version with multiple hidden layers) to explain binary grammaticality judgment data from children aged 4;0-5;0, and elicited-production data from children aged 4;0-5;0 and 5;6-6;6 (
N
=48 per language). In general, the model successfully simulated both children’s judgment and production data, with correlations of
r
=0.5-0.6 and
r
=0.75-0.85, respectively, and also generalized to unseen verbs. Importantly, learners of all five languages showed some evidence of making the types of overgeneralization errors – in both judgments and production – previously observed in naturalistic studies of English (e.g.,
*I’m dancing it
). Together with previous findings, the present study demonstrates that a simple learning model can explain (a) adults’ continuous judgment data, (b) children’s binary judgment data and (c) children’s production data (with no training of these datasets), and therefore constitutes a plausible mechanistic account of the acquisition of verbs’ argument structure restrictions.
To determine the proportion of women with a gynecologic malignancy that complete a survivorship visit when integrating the survivorship program into a routine outpatient gynecologic oncology office ...visit.
In 2017, in an effort to improve the survivorship care for women with gynecologic malignancies, the Program in Women's Oncology at Women and Infants Hospital in Providence, RI instituted a survivorship visit for all patients one month after completion of upfront treatment. This visit took place in the outpatient clinic with the primary gynecologic oncologist present and the nurse practitioner completing the visit. Patients were then referred to subspecialities (nutrition, physical therapy, genetics, urogynecology) for consultation based on needs identified during their survivorship review. We performed a retrospective review of patients completing upfront treatment for gynecologic cancers at our institution. Eligible patients had uterine, ovarian, cervical, or vulvar cancer, and completed treatment with surgery, chemotherapy, radiation, or a combination of these modalities. Records were reviewed to ascertain percentage of patients referred for survivorship visit and the number of patients completing the visit. In addition, we collected information on cancer type and stage, treatment, age, race, and ethnicity.
1072 patients with new diagnoses of primary gynecologic cancers were treated between 2017 and 2019 at Women and Infants Hospital. Of these, 30% of patients were referred for survivorship visit. Patients with ovarian cancer had the highest rate of referral for survivorship visit with 51% referred, while patients with vulvar cancer had the lowest rates of referral with 10% referred. 9% of all patients self-identified as race other than White, and of these, 32% were referred for survivorship visit, compared to 30% of patients identifying as White. During the study period, there was an increase in proportion of referrals across all gynecologic cancers from 16% to 39%.
Survivorship review can be integrated into primary gynecologic oncology office setting to streamline care for patients completing upfront therapy. Further analysis evaluating the impact of stage and specific modality of therapy is warranted to clarify barriers that affect emphasis on transition to survivorship in patients with gynecologic cancers.
Diabetics are at increased risk for fracture, and experience severely impaired skeletal healing characterized by delayed union or nonunion of the bone. The periosteum harbors osteochondral ...progenitors that can differentiate into chondrocytes and osteoblasts, and this connective tissue layer is required for efficient fracture healing. While bone marrow-derived stromal cells have been studied extensively in the context of diabetic skeletal repair and osteogenesis, the effect of diabetes on the periosteum and its ability to contribute to bone regeneration has not yet been explicitly evaluated. Within this study, we utilized an established murine model of type I diabetes to evaluate periosteal cell differentiation capacity, proliferation, and availability under the effect of a diabetic environment. Periosteal cells from diabetic mice were deficient in osteogenic differentiation ability in vitro, and diabetic mice had reduced periosteal populations of mesenchymal progenitors with a corresponding reduction in proliferation capacity following injury. Additionally, fracture callus mineralization and mature osteoblast activity during periosteum-mediated healing was impaired in diabetic mice compared to controls. We propose that the effect of diabetes on periosteal progenitors and their ability to aid in skeletal repair directly impairs fracture healing.
Display omitted
•Periosteum-specific effects contribute to impaired diabetic fracture healing.•Diabetes induces a long-term loss of progenitor osteogenic differentiation capacity.•Diabetes causes loss of periosteal proliferation/differentiation post-fracture.•Advanced glycation end products do not alter periosteal chondrogenic potential.
To determine the effectiveness of sending Christmas cards to participants in randomised controlled trials to increase retention rate at follow-ups, and to explore the feasibility of doing a study ...within a trial (SWAT) across multiple host trials simultaneously.
Randomised SWAT conducted simultaneously across eight host trials.
Eight randomised controlled trials researching various areas including surgery and smoking cessation.
3223 trial participants who were still due at least one follow-up from their host randomised controlled trial.
Participants were randomised (1:1, separately by each host trial) to either received a Christmas card in mid-December 2019 or to not receive a card.
Proportion of participants completing their next follow-up (retention rate) within their host randomised controlled trial.
1469 participants (age 16-94 years; 70% (n=1033) female; 96% (813/847) white ethnicity) across the eight host randomised controlled trials were involved in the analysis (cut short owing to covid-19). No evidence was found of a difference in retention rate between the two arms for any of the host trials when analysed separately or when the results were combined (85.3% (639/749) for cards versus 85.4% (615/720) for no card; odds ratio 0.96, 95% confidence interval 0.71 to 1.29; P=0.77). No difference was observed when comparing just participants who were due a follow-up in the 30 days after receiving the card (odds ratio 0.96, 0.42 to 2.21). No evidence of a difference in time to complete the questionnaire was found (hazard ratio 1.01, 95% confidence interval 0.91 to 1.13; P=0.80). These results were robust to post hoc sensitivity analyses. The cost of this intervention was £0.76 (€0.91; $1.02) per participant, and it will have a carbon footprint of approximately 140 g CO
equivalent per card. One benefit of this approach was the need to only submit one ethics application.
Sending Christmas cards to participants in randomised controlled trials does not increase retention. Undertaking a SWAT within multiple randomised controlled trials at the same time is, however, possible. This approach should be used more often to build an evidence base to support selection of recruitment and retention strategies. Although no evidence of a boost to retention was found, embedding a SWAT in multiple host trials simultaneously has been shown to be possible.
SWAT repository https://www.qub.ac.uk/sites/TheNorthernIrelandNetworkforTrialsMethodologyResearch/FileStore/Filetoupload,846275,en.pdf#search=SWAT%2082.
Despite the remarkable regenerative capacity of skeletal tissues, nonunion of bone and failure of fractures to heal properly presents a significant clinical concern. Stem and progenitor cells are ...present in bone and become activated following injury; thus, elucidating mechanisms that promote adult stem cell-mediated healing is important. Wnt-associated adult stem marker Lgr6 is implicated in the regeneration of tissues with well-defined stem cell niches in stem cell-reliant organs. Here, we demonstrate that Lgr6 is dynamically expressed in osteoprogenitors in response to fracture injury. We used an Lgr6-null mouse model and found that Lgr6 expression is necessary for maintaining bone volume and efficient postnatal bone regeneration in adult mice. Skeletal progenitors isolated from Lgr6-null mice have reduced colony-forming potential and reduced osteogenic differentiation capacity due to attenuated cWnt signaling. Lgr6-null mice consist of a lower proportion of self-renewing stem cells. In response to fracture injury, Lgr6-null mice have a deficiency in the proliferation of periosteal progenitors and reduced ALP activity. Further, analysis of the bone regeneration phase and remodeling phase of fracture healing in Lgr6-null mice showed impaired endochondral ossification and decreased mineralization. We propose that in contrast to not being required for successful skeletal development, Lgr6-positive cells have a direct role in endochondral bone repair.
•Lgr6 expression is enhanced in the periosteum in response to injury•Adult Lgr6-null mice have decreased bone volume•Lgr6-null mice have a lower proportion of skeletal stem cells•Decrease proliferation and reduced ALP activity in the periosteum results in delayed fracture healing in Lgr6-null mice
PDF
