Feasibility Phase Research Articles

Development and feasibility of a mHealth intervention to improve guardians' adherence to children's follow up care after treatment for acute lymphoblastic leukemia in Tanzania: An overview of the GuardiansCan project.

Cancer is a leading cause of death during childhood and in low- and middle-income countries (LMICs) survival rates can be as low as 20%. A leading reason for low childhood cancer survival rates in LMICs such as Tanzania is treatment abandonment. Contributing factors include poor communication between healthcare providers and children's guardians (guardians), insufficient cancer knowledge, and psychological distress. Our aim is to respond to Tanzanian guardians' poor adherence to children's follow-up care after treatment for acute lymphoblastic leukemia with the help of mHealth technology. Our goal is to increase guardians' adherence to children's medications and follow-up visits; and secondly to decrease their psychological distress. Following the Medical Research Council (MRC) Framework for developing and evaluating complex interventions, we will undertake the GuardiansCan project in an iterative phased approach to develop an mHealth intervention for subsequent testing. Public contribution activities will be implemented throughout via a Guardians Advisory Board consisting of guardians of children with acute lymphoblastic leukemia. We will examine the acceptability, feasibility, and perceived impact of public contribution activities via an impact log and semi-structured interviews (Study I). In Phase One (intervention development) we will explore guardians' needs and preferences for the provision of follow-up care reminders, information, and emotional support using focus group discussions and photovoice (Study II). We will then co-design the mHealth intervention with guardians, healthcare professionals, and technology experts using participatory action research (Study III). In Phase Two (feasibility) we will examine clinical, methodological, and procedural uncertainties associated with the intervention and study methods in a single-arm pre-post mixed methods pragmatic feasibility study (Study IV). Data collection for the GuardiansCan project is anticipated to take three years. We plan to commence Study I by recruiting Guardians Advisory Board members in autumn 2023. By systematically following the intervention development and feasibility phases of the MRC Framework, and working alongside an advisory board of guardians, we intend to develop an acceptable, culturally appropriate, feasible, and relevant mHealth intervention with the potential to increase guardians' adherence to children's follow-up care after treatment of acute lymphoblastic leukemia, leading to a positive impact on children's health and chances to survive and reduced suffering for guardians. n/a.

Practitioners' ability to remotely develop understanding for personalised care and support planning: a thematic analysis of multiple data sources from the feasibility phase of the Dementia Personalised Care Team (D-PACT) intervention.

Practitioner understanding of patients' preferences, wishes and needs is essential for personalised health care i.e., focusing on 'what matters' to people based on their individual life situation. To develop such an understanding, dementia practitioners need to use communication practices that help people share their experiences, preferences, and priorities. Following the COVID-19 pandemic, dementia support is likely to continue to be delivered both remotely and in-person. This study analysed multiple sources of qualitative data to examine the views of practitioners, people living with dementia and carers, and researchers on how an understanding of what matters to people living with dementia can be developed remotely via telephone and video call. Access to environmental stimuli, the remote use of visual tools, peoples' tendency to downplay or omit details about their troubles and carers' ability to disclose privately were interpreted, through thematic analysis, to be factors affecting how practitioners sought to develop understanding remotely. Cumulatively, findings show that while remote support created unique challenges to practitioners' ability to develop understanding for personalised care, practitioners developed adaptive strategies to overcome some of these challenges. Further research should examine how, when and for whom these adapted practices for remote personalised care work, informing the development of evidence-based guidance and training on how practitioners can remotely develop the understanding required for personalised care.

O-010 The ULTRA trial: transvaginal ULTRAsound-guided ovarian ablation using the novel May Health device in women with PCOS-related infertility: first–in-human feasibility clinical trial

Abstract Study question Is transvaginal ULTRAsound (TVUS)-guided ovarian ablation using May Health device feasible, safe, and effective in inducing ovulation in Clomiphene citrate and/or Letrozole (CC/LTZ)-resistant PCOS women? Summary answer TVUS-guided ovarian ablation using the May Health device seems feasible, safe and effective in inducing ovulation in PCOS-related anovulatory infertility, with additional, larger studies needed. What is known already Laparoscopic ovarian drilling (LOD) is widely accepted and recommended as an effective second line treatment in PCOS-related infertility. However, it is an invasive procedure that requires general anaesthesia and carries significant risks. Furthermore, the off-the-shelf devices used for LOD are not specifically designed to precisely deliver the desired and effective amount of ablation. In contrast, the May Health device has been designed to induce a precisely calculated amount of ovarian ablation via a much less invasive route without general anaesthesia. May Health therefore transforms an invasive surgical procedure to an office-based technique similar in access to the well-established oocyte retrieval. Study design, size, duration This study included two phase-1 feasibility, single-arm clinical trials running in parallel in the US and EU assessing the May Health Device in performing TVUS-guided ovarian ablation in anovulatory PCOS women resistant to first-line ovulation induction drugs. Sample size was 35 participants with post-procedure follow-up (FU) of 24 months in EU and 12 months in US. Endpoints included procedure feasibility (successful ablation of at least one ovary), safety, and effectiveness (ovulation and pregnancy rates). Participants/materials, setting, methods Seven fertility centres (UK, France, Belgium, US) participated in the trials. Participants were CC/LTZ-resistant PCOS women aged 18-40 years. PCOS was diagnosed according to Rotterdam criteria. Participants underwent TVUS-guided ovarian ablation using May Health device. The initial five participants underwent laparoscopy concurrent with TVUS-ablation. Post-procedure, serum progesterone was measured weekly until confirmation of ovulation or up to 12 weeks. Women were evaluated at 3 and 6 months, then telephoned at 9, 12 and 24 months. Main results and the role of chance Twenty-three participants (mean±sd age, 31.8±3.1years; BMI, 29.8±5.0kg/m2) underwent May Health TVUS-guided ovarian ablation and completed at least three-months FU. Of those, 10 (43.5%) ovulated spontaneously during the first three months. Six more women ovulated between three- and nine-months FU, some with CC/LTZ, giving a total ovulation rate of 69.6% (16/23). Of the 11 participants who completed nine-months FU, five conceived. Two more participants conceived before 9-months giving a total pregnancy rate of 53.8% (7/13). In 19 cases (82.6%), ablation was achieved successfully in both ovaries, while in four cases (17.4%) one of the ovaries was not ablated either because it was too small (as per protocol) (n = 3) or inaccessible (n = 1). Overall, 14 participants experienced 29 adverse events (AEs), of which 25 were mild, two moderate and two severe. Nine mild/moderate AEs were deemed related to the device/ablation procedure. Examples of mild/moderate AEs included mild self-limiting vaginal bleeding (n = 5), pain (n = 5) and headache (n = 2). None of the severe AEs were deemed related to the device/ablation procedure. One participant in phase1a who underwent laparoscopy concurrent with the ablation, sustained a bowel injury involving the ilium near the ileocecal junction. Independent expert investigation concluded that the injury was likely caused by laparoscopic veress needle. Limitations, reasons for caution One possible limitation of this study is the lack of a comparator treatment / placebo arm. However, this was not necessary for this feasibility phase 1 trial. Furthermore, given the nature of TVUS-ovarian ablation, it would be difficult to compare it with other ovulation induction drugs or to a placebo. Wider implications of the findings These preliminary data suggest that the novel May Health device offers a promising office-based second line ovulation inducing procedure for CC/Letrozole-resistant anovulatory PCOS women. Trial registration number NCT03760926

Feasibility Meets Implementation Science: Narrowing the Research-To-Practice Gap for Exercise Activity in Multiple Sclerosis

Background There is a need to identify why multiple sclerosis exercise research is not translating into real-world participation. To lay the foundations of strong clinical research, considering the translational element of implementation science at the feasibility phase of a trial is vital. Methods Document analysis was used to examine document sources on exercise activity interventions designed for people living with multiple sclerosis. Document sources focused on multiple sclerosis research that incorporated exercise prescription elements and behaviour change and were feasibility studies incorporating aspects of implementation science. Results Implementation science should come much earlier than the efficacy or effectiveness research pipeline. An alternate view is outlined where feasibility and implementation science should meet based on case examples that have not yet shown strong efficacy or effectiveness. Findings from our key themes indicate a need for a cyclical iterative approach to the translational process. Multiple aspects of feasibility and how it can be assessed using an implementation science lens to support more successful interventions are provided. The determination of feasibility in behaviour change should involve implementation science as feasibility is drawn on for theory development, optimising the intervention design and quality of implementation strategies, and identifying those delivering the intervention before conducting efficacy and effectiveness research. Conclusions Document analysis methodology is underused in qualitative research and was appropriate to use as it was a very resource, time-efficient and an unobtrusive process that could track change and development to explore the integration of implementation science at the feasibility phase, with the findings indicating the earlier implementation science is introduced into multiple sclerosis exercise interventions the better.

Randomized phase II study of zoledronate dosing every four versus eight weeks in patients with bone metastasis from lung cancer (Hanshin Cancer Group0312)

BackgroundZoledronic acid (ZA) reduces the incidence of skeletal-related events (SREs) in patients with bone metastases from solid tumors. However, the optimal dosing interval of ZA for patients with lung cancer is uncertain. MethodsWe conducted a randomized, open-label, feasibility phase 2 trial at eight Japanese hospitals. Patients with bone metastases from lung cancer were randomly assigned to receive either 4 mg of ZA every four weeks (4wk-ZA) or every eight weeks (8wk-ZA). The primary endpoint was the time to the first SRE and the rate and types of SREs after one year. SREs were defined as pathologic bone fracture, bone radiation therapy or surgery, and spinal cord compression. Secondary endpoints were the SRE incidence at six months, pain assessment, changes in analgesic consumption, serum N-telopeptide, toxicity, and overall survival. ResultsBetween November 2012 and October 2018, 109 patients were randomly assigned to the 4wk-ZA group (54 patients) and the 8wk-ZA group (55 patients). The number of patients who received chemotherapy or molecular-targeted agents was 30 and 23 and 18 and 16 in the 4wk-ZA and 8wk-ZA groups, respectively. The median time to the first SRE could not be calculated because of a low SRE. The time to the first SRE of all patients did not differ between the groups (P = 0.715, HR = 1.18, 95% CI = 0.48, 2.9). The SRE rate of all patients after 12 months was 17.6% (95% CI = 8.4, 30.9%) in the 4wk-ZA and 23.3% (95% CI = 11.8, 38.6%) in the 8wk-ZA group, without significant differences between the groups. There was no difference in any secondary endpoint between groups, and these endpoints did not differ among treatment modalities. ConclusionsAn eight-week ZA interval does not increase the SRE risk for patients with bone metastasis from lung cancer and could be considered clinically.

Feasibility of combining temsirolimus to vincristine, dactinomycin, cyclophosphamide, and vincristine and irinotecan chemotherapy for children with intermediate-risk rhabdomyosarcoma: A report from Children's Oncology Group.

Temsirolimus has shown in vivo activity against rhabdomyosarcoma (RMS). We aimed to determine the feasibility of incorporating temsirolimus within the standard Children's Oncology Group (COG) chemotherapy backbone of vincristine, actinomycin-D, and cyclophosphamide (VAC) alternating with vincristine and irinotecan (VI) in children with intermediate-risk (IR) RMS. The feasibility phase of the COG IR-RMS trial, ARST1431 (NCT02567435), assigned 10 patients to receive 15mg/m2 /dose (dose level 1) of temsirolimus on days 1, 8, and 15 of each of three weekly VAC and VI cycles for the first 12weeks of induction chemotherapy. The primary endpoint of the feasibility phase was to establish the safe dose and safety of combining temsirolimus with VAC/VI. The combination regimen was deemed feasible if less than 40% of patients developed a priori defined nonhematological dose-limiting toxicities (DLTs). Ten patients (seven males and three females; median age=4.5 years [range: 0.2-14.4years]) with IR-RMS were enrolled and received dose level 1 of temsirolimus. Eight patients had FOXO1-negative disease, while two had FOXO1-positive disease. Two patients had metastatic disease. Of 10 patients, two developed DLTs: grade 3 oral mucositis and pneumonitis. Four patients (40%) had grade 4 neutropenia. No treatment-related mortality occurred. The median duration of the completion of the feasibility phase was 12.1weeks (range: 11.7-15weeks). Weekly temsirolimus at 15mg/m2 /dose during VAC/VI chemotherapy was feasible and well tolerated. The efficacy of this regimen is currently being tested in a phase III randomized trial against VAC/VI chemotherapy alone in the ARST1431 trial.

Feasibility and acceptability of bubble continuous positive airway pressure oxygen therapy for the treatment of childhood severe pneumonia and hypoxaemia in Bangladeshi children

Effective management of hypoxaemia is key to reducing pneumonia deaths in children. In an intensive care setting within a tertiary hospital in Bangladesh, bubble continuous positive airway pressure (bCPAP) oxygen therapy was beneficial in reducing deaths in this population. To inform a future trial, we investigated the feasibility of introducing bCPAP in this population in non-tertiary/district hospitals in Bangladesh. We conducted a qualitative assessment using a descriptive phenomenological approach to understand the structural and functional capacity of the non-tertiary hospitals (Institute of Child and Mother Health and Kushtia General Hospital) for the clinical use of bCPAP. We conducted interviews and focus group discussions (23 nurses, seven physicians, 14 parents). We retrospectively (12 months) and prospectively (three months) measured the prevalence of severe pneumonia and hypoxaemia in children attending the two study sites. For the feasibility phase, we enrolled 20 patients with severe pneumonia (age two to 24 months) to receive bCPAP, putting in place safeguards to identify risk. Retrospectively, while 747 of 3012 (24.8%) children had a diagnosis of severe pneumonia, no pulse oxygen saturation information was available. Of 3008 children prospectively assessed with pulse oximetry when attending the two sites, 81 (3.7%) had severe pneumonia and hypoxaemia. The main structural challenges to implementation were the inadequate number of pulse oximeters, lack of power generator backup, high patient load with an inadequate number of hospital staff, and inadequate and non-functioning oxygen flow meters. Functional challenges were the rapid turnover of trained clinicians in the hospitals, limited post-admission routine care for in-patients by hospital clinicians due to their extreme workload (particularly after official hours). The study implemented a minimum of four hourly clinical reviews and provided oxygen concentrators (with backup oxygen cylinders), and automatic power generator backup. Twenty children with a mean age of 6.7 (standard deviation (SD) = 5.0)) months with severe pneumonia and hypoxaemia (median (md) SpO2 = 87% in room air, interquartile range (IQR) = 85-88)) with cough (100%) and severe respiratory difficulties (100%) received bCPAP oxygen therapy for a median of 16 hours (IQR = 6-16). There were no treatment failures or deaths. Implementation of low-cost bCPAP oxygen therapy is feasible in non-tertiary/district hospitals when additional training and resources are allocated.

TRENDS AND OUTCOMES IN FLIPPED LEARNING-BASED INSTRUCTION IN TEACHING READING: SYSTEMATIC LITERATURE REVIEW

Despite the flipped learning growing popularity, empirical research to increase students' reading abilities is still lacking. The majority of research concentrates on students' impressions of the English language rather than particular language abilities. If there is, speaking, listening, and writing is dominant. This systematic literature review summarizes study findings on trends and outcomes of flipped learning-based instruction in teaching reading. The identification, screening, feasibility, and inclusion phase found thirty-one articles between 2015 and 2022 from the Scopus database with a premium Scopus account to access all sources without limits. The results showed that the research trend of flipped learning in teaching reading was less attractive to researchers than other English skills. It can be seen from the lack of publications from year to year and even tends to decline until May 2022. Further research on flipped learning in teaching reading can enrich the literature on knowledge. In addition, Flipped Learning has positive outcomes in influencing students' performance, especially if combined with other methods. For future research, several different research scopes can be considered, such as creating models or designs to apply flipped learning to students' reading performance and comprehension.

Tungsten trioxide integrated all-fiber phase shifter

This work proposes an all-fiber phase shifter based on tapered optical fiber spin coated with tungsten trioxide (WO3). Different WO3 coating thickness was tested by varying the spin coating time from 30 to 150 s at constant 1000 rpm. Evanescent field induced by the non-adiabatic taper generated thermal optic effect through interaction with the WO3 layer, which changed its refractive index and produced phase shifting effect. The optimum spin coating time of 120 s yielded maximum phase shift of 2.52 π with wavelength shift coefficient of 0.0859 nm/mW as 980 nm pump power was varied up to 220 mW. Integration of phase shifter in fiber laser cavity produced wavelength tuning with shift coefficient of about 0.06 nm/mW. This work presents a feasible all-fiber phase shifter with simple fabrication and operation that suits current need in communication field.

Feasibility and Acceptability of an Internet of Things-Enabled Sedentary Behavior Intervention: Mixed Methods Study.

Encouraging office workers to break up prolonged sedentary behavior (SB) at work with regular microbreaks can be beneficial yet challenging. The Internet of Things (IoT) offers great promise for delivering more subtle and hence acceptable behavior change interventions in the workplace. We previously developed an IoT-enabled SB intervention, called WorkMyWay, by applying a combination of theory-informed and human-centered design approaches. According to the Medical Research Council's framework for developing and evaluating complex interventions such as WorkMyWay, process evaluation in the feasibility phase can help establish the viability of novel modes of delivery and identify facilitators and barriers to successful delivery. This study aims to evaluate the feasibility and acceptability of the WorkMyWay intervention and its technological delivery system. A mixed methods approach was adopted. A sample of 15 office workers were recruited to use WorkMyWay during work hours for 6 weeks. Questionnaires were administered before and after the intervention period to assess self-report occupational sitting and physical activity (OSPA) and psychosocial variables theoretically aligned with prolonged occupational SB (eg, intention, perceived behavioral control, prospective memory and retrospective memory of breaks, and automaticity of regular break behaviors). Behavioral and interactional data were obtained through the system database to determine adherence, quality of delivery, compliance, and objective OSPA. Semistructured interviews were conducted at the end of the study, and a thematic analysis was performed on interview transcripts. All 15 participants completed the study (attrition=0%) and on average used the system for 25 tracking days (out of a possible 30 days; adherence=83%). Although no significant change was observed in either objective or self-report OSPA, postintervention improvements were significant in the automaticity of regular break behaviors (t14=2.606; P=.02), retrospective memory of breaks (t14=7.926; P<.001), and prospective memory of breaks (t14=-2.661; P=.02). The qualitative analysis identified 6 themes, which lent support to the high acceptability of WorkMyWay, though delivery was compromised by issues concerning Bluetooth connectivity and factors related to user behaviors. Fixing technical issues, tailoring to individual differences, soliciting organizational supports, and harnessing interpersonal influences could facilitate delivery and enhance acceptance. It is acceptable and feasible to deliver an SB intervention with an IoT system that involves a wearable activity tracking device, an app, and a digitally augmented everyday object (eg, cup). More industrial design and technological development work on WorkMyWay is warranted to improve delivery. Future research should seek to establish the broad acceptability of similar IoT-enabled interventions while expanding the range of digitally augmented objects as the modes of delivery to meet diverse needs.

Some observations on remote delivery of eye‐movement desensitisation and reprocessing to people with intellectual disabilities

AbstractIt is increasingly recognised that many people with intellectual disabilities suffer from post‐traumatic stress disorder (PTSD). Eye‐movement desensitisation and reprocessing (EMDR) has been proposed as a potentially helpful intervention that is less reliant on verbal skills than other effective treatments for PTSD and therefore could be more effective than verbal interventions for people with intellectual disabilities. The Trauma‐AID project is a randomised clinical trial (RCT) evaluating the effectiveness of a bespoke EMDR protocol for adults with intellectual disability and PTSD, which incorporates a prolonged phase of Psycho‐Education and Stabilisation (PES) prior to the trauma confrontation phase of EMDR. The COVID‐19 pandemic struck during the feasibility phase of the Trauma‐AID project, necessitating a second feasibility study to evaluate the acceptability and feasibility of remote or hybrid delivery of the PES + EMDR protocol. To this end, we conducted two online surveys of therapists followed by interviews with clients, carers and senior therapists. The surveys were analysed descriptively. Content analysis was used for client and carer interviews, and framework analysis for therapist interviews. All stakeholders reported positive experiences of EMDR; however, some challenges were identified. The majority of clients, carers and therapists interviewed reported that the intervention, whether PES alone or the full PES‐EMDR package, had improved symptoms of PTSD and psychological well‐being, and carers also reported decreases in challenging behaviour. A full account of the data is provided in four Supplementary Digital files. PES‐EMDR therapy appears both feasible and acceptable for clients with intellectual disabilities and therapists, whether delivered face‐to‐face or in a remote or hybrid mode, though remote working appears easier for the PES phase than the EMDR phase of the intervention.

A participatory process to design an app to improve adherence to anti-osteoporotic therapies: A development and usability study.

The aim of the study was to develop an app to improve patients' adherence to therapy for osteoporosis and to test its usability. In Phase I, the app functions needed to improve medication adherence were identified through a focus group with six patients with osteoporosis and a joint interview with two bone specialists. The app prototype was then developed (Phase II) and refined after its feasibility testing (Phase III) for 13-25 days by eight patients. Finally, the app underwent usability testing (Phase IV) for 6 months by nine other patients. The mHealth App Usability Questionnaire (MAUQ) was used to collect the assessment of the app by the 17 patients. The final version of the app provided information on osteoporosis, allowed patients to contact the bone specialist for an additional consultation, and generated a reminder for taking medications accompanied by feedback on adherence. The assessment of the app was positive but evaluations differed between the feasibility and usability testing, with the former displaying a significantly (p ≤ .05) better assessment across all MAUQ items. In this study, we tested an app for improving adherence to medical therapies in patients with osteoporosis. The usability testing revealed a lower "patient-centered" performance of the app as compared to that observed during the feasibility phase. Future developments of the study include increasing the testing cohort and adding a technical support during the usability testing.

Compensation method for spatial phase distortion based on autocorrelation in laser heterodyne detection

The signal-to-noise ratio (SNR) of heterodyne detection is seriously reduced by the spatial phase distortion, so the compensation method of the phase distortion is of great significance for improving the performance of the heterodyne system. By replacing the single detector with an array detector in the system, the previous compensation method based on sequence shift and optimization algorithm has a certain effect. However, the method also has various shortcomings, such as long processing time, poor search stability, and possible false alarm, which severely limits its practical application. To solve the above-mentioned problems, the autocorrelation operation is used to achieve the equiphase superposition of the signals output by the elements of the array detector, thereby realizing the phase compensation. In comparison to the previous method, our method does not need an optimization algorithm, which avoids the long iterative operations and considerably improves the processing efficiency. Besides, this method avoids the false alarm caused by the optimization algorithm. The numerical calculation indicates that in case of severe phase distortion, the proposed method can increase the SNR by dozens of dB compared with the single-point detector system, thus proving the effectiveness of this method. The study results may provide a feasible and effective phase compensation method for improving and promoting the laser heterodyne detection performance.

Study protocol for the implementation and evaluation of a digital-robotic-based intervention for nurses and patients in a hospital: a quantitative and qualitative triangulation based on the Medical Research Council (MRC) framework for developing and evaluating complex interventions.

Nurses spend part of their working time on non-nursing tasks. Unnecessary walking distances and the assumption of service activities and other non-care-related tasks take up a lot of space, which reduces the time for direct patient care and demonstrably increases the dissatisfaction of the persons involved. The REsPonSe project aims to relieve nursing staff by using a smartphone app for communication in combination with an autonomous service robot to reduce walking distances and service activities. The technical systems are tested on a nuclear medicine ward and are intended to reduce the radiation exposure of the staff. The aim of this study is to test and evaluate the use and intervention of the technical systems, the acceptance of the users and the change in the utilisation of the nursing service. In addition to findings on usability and manageability, effects on nursing practice, as well as facilitating and inhibiting contextual factors for implementation, will be identified. The Medical Research Council (MRC) Framework for Developing and Evaluating for Complex Interventions was chosen as the theoretical basis. The data collection in the Feasibility and Evaluation phase is a triangulation of quantitative and qualitative methods. Standardised observations are planned to collect data on non-care activities and walking distances, and a survey of utilisation by use of a questionnaire based on the NASA TLX. Qualitative individual interviews with patients and group discussions with nursing staff will be conducted. Statements on the subjective experiences, as well as the evaluation of the use of the digital-robotic system in the clinical setting, will be collected. The descriptive evaluation of the usage and retrieval data will provide information on duration, time, requests, and reduced contact times, as well as error and fault messages. The evaluation study will make it possible to represent a variety of perspectives from different interest groups. The results should contribute to the definition of implementation and evaluation criteria and facilitate the integration of digital-robotic assistance systems in nursing acute inpatient settings. The trial was registered with the German Clinical Trials Register (DRKS) on 16.02.2022: DRKS00028127.

NIMG-05. DYNAMIC SUSCEPTIBILITY CONTRAST MRI IN THE EVALUATION OF BRAIN METASTASES: CURRENT PRACTICE REVIEW AND RATIONALE FOR STUDY OF BASELINE PERFUSION IMAGING PRIOR TO STEREOTACTIC RADIOSURGERY (STARBEAM-X)

Abstract Stereotactic radiosurgery (SRS) is an established focal treatment for brain metastases with high local control rates. An important side-effect of SRS is the development of radionecrosis. On conventional MR imaging, radionecrosis and tumour progression often have similar appearances, but have contrasting management approaches. Perfusion MR imaging is often used in the post-treatment setting in order to help distinguish between the two, but image interpretation can be fraught with challenges.Perfusion MR plays an established role in the baseline and post-treatment evaluation of primary brain tumours and a number of studies have concentrated on the value of perfusion imaging in brain metastases. Of the parameters generated, relative cerebral blood volume is the most widely used variable in terms of its clinical value in differentiating between radionecrosis and tumour progression.Although it has been suggested that the rCBV tends to be elevated in active metastatic disease following treatment with radiosurgery, but not with treatment-related changes, the literature available on interpretation of the ratios provided in the context of defining tumour progression is not consistent.We provide an overview of the role perfusion MRI plays in the assessment of brain metastases and introduces the rationale for the STARBEAM-X study (Study of assessment of radionecrosis in brain metastases using MR perfusion extra imaging), which will prospectively evaluate baseline perfusion imaging in brain metastases. We present here the results of the first three patients recruited to the feasibility phase of this study. We hope this study will allow insight into the vascular appearance of metastases from different primary sites, and aid in the interpretation of post-treatment perfusion imaging.

Bihormonal Artificial Pancreas With Closed-Loop Glucose Control vs Current Diabetes Care After Total Pancreatectomy

Glucose control in patients after total pancreatectomy is problematic because of the complete absence of α- and β-cells, leading to impaired quality of life. A novel, bihormonal artificial pancreas (BIHAP), using both insulin and glucagon, may improve glucose control, but studies in this setting are lacking. To assess the efficacy and safety of the BIHAP in patients after total pancreatectomy. This randomized crossover clinical trial compared the fully closed-loop BIHAP with current diabetes care (ie, insulin pump or pen therapy) in 12 adult outpatients after total pancreatectomy. Patients were recruited between August 21 and November 16, 2020. This first-in-patient study began with a feasibility phase in 2 patients. Subsequently, 12 patients were randomly assigned to 7-day treatment with the BIHAP (preceded by a 5-day training period) followed by 7-day treatment with current diabetes care, or the same treatments in reverse order. Statistical analysis was by Wilcoxon signed rank and Mann-Whitney U tests, with significance set at a 2-sided P < .05. The primary outcome was the percentage of time spent in euglycemia (70-180 mg/dL [3.9-10 mmol/L]) as assessed by continuous glucose monitoring. In total, 12 patients (7 men and 3 women; median [IQR] age, 62.5 [43.1-74.0] years) were randomly assigned, of whom 3 did not complete the BIHAP phase and 1 was replaced. The time spent in euglycemia was significantly higher during treatment with the BIHAP (median, 78.30%; IQR, 71.05%-82.61%) than current diabetes care (median, 57.38%; IQR, 52.38%-81.35%; P = .03). In addition, the time spent in hypoglycemia (<70 mg/dL [3.9 mmol/L]) was lower with the BIHAP (median, 0.00% [IQR, 0.00%-0.07%] vs 1.61% [IQR, 0.80%-3.81%]; P = .004). No serious adverse events occurred. Patients using the BIHAP after total pancreatectomy experienced an increased percentage of time in euglycemia and a reduced percentage of time in hypoglycemia compared with current diabetes care, without apparent safety risks. Larger randomized trials, including longer periods of treatment and an assessment of quality of life, should confirm these findings. trialregister.nl Identifier: NL8871.

Promoting empowerment for people living with dementia in nursing homes: Development and feasibility evaluation of an empowerment program.

ObjectivesThis article describes the development and feasibility evaluation of an empowerment program for people living with dementia in nursing homes.MethodsDevelopment and feasibility evaluation of the empowerment program was guided by the British Medical Research Council’s (MRC) framework. In the developmental phase, we used intervention mapping to develop the theory- and evidence-based intervention. During the feasibility phase, two care teams utilised the program from September to December 2020. We evaluated the feasibility in terms of demand, acceptability, implementation, practicality, integration and limited efficacy.FindingsThis study showed that, according to healthcare professionals, the program was feasible for promoting empowerment for people living with dementia in a nursing home. Healthcare professionals mentioned an increased awareness regarding the four themes of empowerment (sense of identity, usefulness, control and self-worth), and greater focus on the small things that matter to residents. Healthcare professionals experienced challenges in involving family caregivers.ConclusionAn important step is to take into account the implementation prerequisites that follow from our findings, and to further investigate feasibility, as the use of the program and data collection was hindered by the COVID-19 pandemic. Subsequent research could investigate the effects of the empowerment program.

1241P Phase Ib study of futibatinib plus pembrolizumab in patients with advanced or metastatic solid tumors: Tolerability results and antitumor activity in esophageal carcinoma

Combination therapy using FGFR inhibitors and Immune checkpoint inhibitors (ICIs) are being explored as a novel strategy for cancer patients (pts). Here, we report the safety and tolerability of FGFR inhibitor futibatinib plus pembrolizumab in pts with advanced (adv) or metastatic solid tumors and first results for preliminary antitumor activity in pts with esophageal carcinoma (EC). This study consists of Feasibility phase (FP) and Expansion phase (EP). In FP, pts with adv or metastatic solid tumors harboring FGF/FGFR abnormalities received futibatinib 20 mg once daily (QD) plus pembrolizumab 200 mg every 3weeks. In EP, pts with ICIs naive (Cohort A) or ICIs refractory (Cohort B) for adv or metastatic EC harboring FGFR mRNA overexpression who have received at least one prior therapy with a fluorouracil and platinum-based drug received futibatinib plus pembrolizumab at the recommended dose (RD) determined in FP. Primary endpoint was dose-limiting toxicity (DLT) in FP and overall response rate (ORR) in EP; Secondary endpoints included treatment-related adverse events (TRAEs) and disease control rate (DCR). As of November 29, 2021, 11 pts in FP, 9 pts (Cohort A) and 10 pts (Cohort B) in EP were enrolled. No DLTs were observed in FP and the RD of futibatinib in combination with pembrolizumab was determined 20 mg QD. Most common TRAEs in FP (N=11; all grade, grade ≥3) were hyperphosphatemia (91%, 27%), nausea (36%, 0%) and diarrhea (27%, 0%). As results of the interim analysis in EP, confirmed partial responses (PRs) were observed in 4 pts with squamous cell carcinoma (sq) in Cohort A; ORR was 44% with DCR of 78%. In Cohort B, confirmed PRs were observed in 2 pts [1 sq pt; 1 adenocarcinoma (adeno) pt]; ORR was 20% with DCR of 60%. Futibatinib plus pembrolizumab showed well-tolerability and manageable safety profile in pts with adv or metastatic solid tumors. Preliminary antitumor activity was observed not only in ICIs naïve but also in ICIs refractory adv or metastatic EC pts regardless of sq and adeno. Enrollment in EP is ongoing including an additional cohort for ICIs naïve 1st line adv EC and ICIs refractory adv NSCLC pts.

Improved methodology for affordable, reliable deep building renovations

European Union energy efficiency goals put refurbishments in focus as the existing building stock takes a high share in the final energy consumption meanwhile current refurbishment rates are lower than expected. This research attempts to answer the question: How can renovation processes be improved to raise renovation rates? The methodology development process consisted of identifying the methodological background, the phases and steps of the renovation process and the validation strategies. As a result, five methodological phases were identified. Renovations start with the Feasibility phase where a simple financial and technical assessment is carried out. During the Preparation phase necessary information is collected which results in a calibrated simulation model that can support the design. In the Design phase the renovation options are developed and assessed together with a business plan for financing the implementation through renovation cycles. The renovation measures are carried out during the Implementation phase. In the Operation phase the performance of the refurbished building is monitored and improved. The developed methodology is expected to provide more affordable, reliable building renovations, which reduces the performance gap, the upfront investment and the disruption of user life by reducing overall time on site. This results in an increased investment efficiency leading to higher uptake of refurbishments.

A Psychological Support Intervention to Help Injured Athletes "Get Back in the Game": Design and Development Study.

BackgroundAfter a serious knee injury, up to half of athletes do not return to competitive sport, despite recovering sufficient physical function. Athletes often desire psychological support for the return to sport, but rehabilitation clinicians feel ill-equipped to deliver adequate support.ObjectiveWe aimed to design and develop an internet-delivered psychological support program for athletes recovering from knee ligament surgery.MethodsOur work for developing and designing the Back in the Game intervention was guided by a blend of theory-, evidence-, and target population–based strategies for developing complex interventions. We systematically searched for qualitative evidence related to athletes’ experiences with, perspectives on, and needs for recovery and return to sport after anterior cruciate ligament (ACL) injury. Two reviewers coded and synthesized the results via thematic meta-synthesis. We systematically searched for randomized controlled trials reporting on psychological support interventions for improving ACL rehabilitation outcomes in athletes. One reviewer extracted the data, including effect estimates; a second reviewer checked the data for accuracy. The results were synthesized descriptively. We conducted feasibility testing in two phases—(1) technical assessment and (2) feasibility and usability testing. For phase 1, we recruited clinicians and people with lived experience of ACL injury. For phase 2, we recruited patients aged between 15 and 30 years who were within 8 weeks of ACL reconstruction surgery. Participants completed a 10-week version of the intervention and semistructured interviews for evaluating acceptability, demand, practicality, and integration. This project was approved by the Swedish Ethical Review Authority (approval number: 2018/45-31).ResultsThe following three analytic themes emerged from the meta-synthesis (studies: n=16; participants: n=164): (1) tools or strategies for supporting rehabilitation progress, (2) barriers and facilitators for the physical readiness to return to sport, and (3) barriers and facilitators for the psychological readiness to return to sport. Coping strategies, relaxation, and goal setting may have a positive effect on rehabilitation outcomes after ACL reconstruction (randomized controlled trials: n=7; participants: n=430). There were no trials of psychological support interventions for improving the return to sport. Eleven people completed phase 1 of feasibility testing (technical assessment) and identified 4 types of software errors, which we fixed. Six participants completed the feasibility and usability testing phase. Their feedback suggested that the intervention was easy to access and addressed the needs of athletes who want to return to sport after ACL reconstruction. We refined the intervention to include more multimedia content and support access to and the use of the intervention features.ConclusionsThe Back in the Game intervention is a 24-week, internet-delivered, self-guided program that comprises 7 modules that complement usual rehabilitation, changes focus as rehabilitation progresses, is easy to access and use, and includes different psychological support strategies.