Personalised perioperative dosing of ivabradine in noncardiac surgery: a single-centre, randomised, placebo-controlled, double-blind feasibility pilot trial.

BACKGROUND: Perioperative myocardial injury after noncardiac surgery is associated with postoperative mortality. Heart rate (HR) is an independent risk factor for perioperative myocardial injury. In this pilot trial we tested the feasibility of a randomised, placebo-controlled trial of personalised HR-targeted perioperative ivabradine. METHODS: This was a single-centre, randomised, placebo-controlled, double-blind, parallel group, feasibility pilot trial conducted at Geneva University Hospitals. We included patients ≥75 yr old or ≥45 yr old with cardiovascular risk factors planned for intermediate- or high-risk surgery. Patients were randomised to receive ivabradine (2.5, 5.0, or 7.5 mg) or placebo according to their HR, twice daily, from the morning of surgery until postoperative day 2. Primary outcomes were appropriate dosage and blinding success rates. RESULTS: Between October 2020 and January 2022, we randomised 78 patients (recruitment rate of 1.3 patients week-1). Some 439 of 444 study drug administrations were adequate (99% appropriate dosage rate). The blinding success rate was 100%. There were 137 (31%) administrations of Pill A (placebo in both groups for HR ≤70 beats min-1). Nine (11.5%) patients had a high-sensitive cardiac troponin T elevation ≥14 ng L-1 between any two measurements. The number of bradycardia episodes was eight in the placebo group and nine in the ivabradine group. CONCLUSIONS: This pilot study demonstrates the feasibility of, and provides guidance for, a future trial testing the efficacy of personalised perioperative ivabradine. Future studies should include patients at higher risk of cardiac complications. CLINICAL TRIAL REGISTRATION: NCT04436016.

A web-based physical activity intervention targeting affect regulation: a randomized feasibility trial.

Early career professionals (ECPs) are a critical target for physical activity (PA) promotion. Affect contributes to an established PA intention-behaviour gap and is pertinent among ECPs. OBJECTIVE: The purpose of this study was to examine the feasibility and acceptability of a web-based intervention and explore the effects on secondary outcomes (moderate-to-vigorous PA (MVPA), emotion regulation, multi-process action control constructs). METHODS: Adults aged 25-44 who were employed at least part-time in a desk-based job and not meeting PA guidelines (<150 min MVPA) were recruited and randomized into a 6-week online intervention integrating acceptance and commitment principles and affect regulation strategies, or a control group. RESULTS: Forty adults were recruited and randomized to the web-based intervention (n = 21) and waitlist control (n = 19). The recruitment rate was 29%, retention was 75%, engagement was 68%, and satisfaction was high in both quantitative and qualitative assessment. Participants allocated to the intervention improved MVPA (ηp2=0.30), emotion regulation (ηp2 =0.49), behavioural regulation (ηp2=0.53), affective attitude (ηp2=0.23), identity (ηp2=0.24), and constructs of mindfulness (ηp2=0.44), and valued living (ηp2=0.20). CONCLUSIONS: Primary outcomes concerning feasibility were adequate and secondary outcomes improved, suggesting a full-scale randomized controlled trial is feasible with minor modifications. A large-scale study is warranted to establish intervention effectiveness.

Acceptability and feasibility of a theatre-based wellness programme to support people living with long COVID: a single-arm feasibility study.

OBJECTIVES: To determine acceptability and feasibility of a theatre-based wellness programme to support the health and well-being of people with long COVID. DESIGN: Single-group, repeated-measures feasibility study. SETTING: Community centre and online. PARTICIPANTS: Adults with diagnosed long COVID experiencing breathlessness, pain and/or loneliness. INTERVENTION: Six-week participatory creative programme delivered to one online and one in-person group facilitated by movement, voice and drama consultants using breathing, visualisation, singing, poetry, storytelling and movement exercises. PRIMARY OUTCOME MEASURES: Programme acceptability and feasibility measured via uptake, reasons for non-attendance and barriers to engagement. SECONDARY OUTCOME MEASURES: Feasibility of recruitment and data collection procedures measured through proportion of missing data and follow-up rates, mechanisms of action of the programme identified through qualitative interviews, changes in mental health, well-being, quality of life, loneliness, social support, fatigue, breathlessness and post-COVID-19 functional status at 8-week follow-up. RESULTS: 21 people expressed interest in participating, 20 people took part in the programme, 19 completed baseline and 16 completed follow-up assessments. Participants attended an average of 4.8 of 6 sessions (SD=1.5, range 2-6). Exploratory analyses demonstrated significant improvements in self-rated health (t-test mean difference=0.12, 95% CI=0.00, 0.23, p=0.04) and chronic fatigue symptoms (mean difference=-3.50, 95% CI=-6.97, -0.03, p=0.05) at 8 weeks. Key mechanisms of action that supported health and well-being included: increased sense of community, illness acceptance, experiencing joy, increased confidence in managing everyday life, increased ability to relax and reconnection with previous identity. Barriers to engagement included: activities being outside of the participant's comfort zone, ongoing long COVID symptoms, emotional consequences of sharing experiences and connectivity and connecting online. CONCLUSIONS: A 6-week theatre-based programme was perceived as acceptable to most participants and resulted in some positive psychosocial impacts. The findings provide a rationale for supporting the ongoing development and scale-up of this and related arts programmes to support people living with long COVID.

A group intervention for pregnant multiparas with fear of childbirth: A protocol of a feasibility study of the MOTIVE trial.

BACKGROUND: Although research interest in fear of childbirth has increased, interventions targeting especially multiparas with fear of childbirth have been overlooked, although untreated fear can cause serious adverse effects on the mother and the whole family. Thus MOTIVE (Multiparas overcoming Childbirth Fear Through Intervention and Empowerment), an intervention for pregnant multiparas with fear of childbirth, was designed. METHODS: This is a protocol of a single-arm non-randomized feasibility study of the MOTIVE trial with a mixed-methods design. The primary aim of the intervention is to assist pregnant multiparas with fear of childbirth, with the desired outcome to alleviate fear. MOTIVE consists of four group sessions (2 h each); three during pregnancy and one after giving birth and in addition of a phone call after birth. The intervention is provided by a midwife and a psychiatric nurse at the maternity hospital. Quantitative data will be gathered via self-report questionnaires at three time points, at baseline, at 4 weeks post-baseline and post-intervention. Qualitative data will be gathered by diaries, open-ended questions from post-intervention questionnaires, and individual interviews. The target is to assemble four groups of four multiparas over a 12-month period. DISCUSSION: The findings will provide insights into the feasibility and acceptability of the intervention and will inform revisions to it. The results will guide the development of a definitive, larger-scale trial evaluation to further examine the efficacy of the refined intervention.

Ultra-high-frequency ultrasound (48-70 MHz) is a promising tool for improved gastrointestinal diagnostics in infants.

AIM: To investigate the clinical feasibility of ultra-high-frequency abdominal ultrasound (UHFUS) scans of preterm and term infants. METHODS: Prospectively, 19 healthy term newborn infants were examined with conventional ultrasound (CUS) (Toshiba, Aplio i700, linear probe 14L5) and UHFUS (Visualsonics VevoMD, linear probes UHF48 and UHF70) according to a standardised protocol. Measurements of wall thickness were performed for; stomach, small intestine, colon and peritoneum. Five preterm infants, with or without suspected necrotising enterocolitis (NEC), were also examined with UHF48. Of these, only one was later diagnosed with NEC. RESULTS: Differences between CUS and UHFUS (UHF48) were found in measurements of thickness; for peritoneum 0.25 versus 0.13 mm (p < 0.001), small intestine 0.76 versus 0.64 mm (p = 0.039) and colon 0.7 versus 0.47 mm (p < 0.001) in healthy term infants. Gaining frequency from 46 to 71 MHz showed a mean reduction in measurements of peritoneum from 0.13 to 0.09 mm (p < 0.001). One preterm infant with NEC showed a fivefold and twofold increase in peritoneal and gastrointestinal wall thickness respectively, compared to healthy preterm infants. CONCLUSION: UHFUS was a clinically feasible, promising method with potential to improve gastrointestinal diagnostics in infants. Lower peritoneum thickness and gastrointestinal wall thickness were demonstrated with UHFUS compared to CUS, suggesting an overestimation by CUS.

Impact of Fruit and Vegetable Enzyme Supplementation on Aerobic Performance and Lactate Response in Older Adults Following High-Intensity Interval Exercise Through Exergaming: Randomized Experimental Matched-Pair Study.

Background: Exercise offers substantial health benefits but can induce oxidative stress and inflammation, especially in high-intensity formats such as high-intensity interval exercise (HIIE). Exergaming has become an effective, enjoyable fitness tool for all ages, particularly older adults. Enzyme supplements may enhance exercise performance by improving lactate metabolism and reducing oxidative stress. Objective: This study investigates the efficacy of fruit and vegetable enzyme supplementation in modulating fatigue and enhancing aerobic capacity in older adults following HIIE through exergaming. Methods: The study recruited 16 older adult female participants and allocated them into 2 distinct groups (enzyme and placebo) based on their pretest lactate levels. This division used pairwise grouping to guarantee comparability between the groups, ensuring the integrity of the results. They engaged in HIIE using Nintendo Switch Ring Fit Adventure, performing 8 sets of 20 seconds of maximum effort exercise interspersed with 30 seconds of rest, totaling 370 seconds of exercise. Key metrics assessed included blood lactate levels, heart rate, rating of perceived exertion, and training impulse. Participants in the enzyme group were administered a fruit and vegetable enzyme supplement at a dosage of 30 mL twice daily over a period of 14 days. Results: The enzyme group showed significantly lower blood lactate levels compared to the placebo group, notably after the fourth (mean 4.29, SD 0.67 vs mean 6.34, SD 1.17 mmol/L; P=.001) and eighth (mean 5.84, SD 0.63 vs mean 8.20, SD 1.15 mmol/L; P<.001) exercise sessions. This trend continued at 5 minutes (mean 6.85, SD 0.82 vs mean 8.60, SD 1.13 mmol/L; P=.003) and 10 minutes (mean 5.91, SD 1.16 vs mean 8.21, SD 1.27 mmol/L; P=.002) after exercise. Although both groups exceeded 85% of their estimated maximum heart rate during the exercise, enzyme supplementation did not markedly affect the perceived intensity or effort. Conclusions: The study indicates that fruit and vegetable enzyme supplementation can significantly reduce blood lactate levels in older adults following HIIE through exergaming. This suggests a potential role for these enzymes in modulating lactate production or clearance during and after high-intensity exercise. These findings have implications for developing targeted interventions to enhance exercise tolerance and recovery in older adults.

Potential applications of 7 Tesla magnetic resonance imaging in paediatric neuroimaging: Feasibility and challenges.

The integration of 7 Tesla magnetic resonance imaging (7 T MRI) in adult patients has marked a revolutionary stride in radiology. In this article we explore the feasibility of 7 T MRI in paediatric practice, emphasizing its feasibility, applications, challenges, and safety considerations. The heightened resolution and tissue contrast of 7 T MRI offer unprecedented diagnostic accuracy, particularly in neuroimaging. Applications range from neuro-oncology to neonatal brain imaging, showcasing its efficacy in detecting subtle structural abnormalities and providing enhanced insights into neurological conditions. Despite the promise, challenges such as high cost, discomfort, and safety concerns necessitate careful consideration. Research suggests that, with precautions, 7 T MRI is feasible in paediatrics, yet ongoing studies and safety assessments are imperative.

Contextual factors related to vector-control interventions for malaria: a scoping review and evidence and gap map protocol.

Objective: This scoping review will identify existing literature regarding contextual factors relevant to vector-control interventions to prevent malaria. We will use the findings of the scoping review to produce an interactive evidence and gap map. The map will assist in the priority setting, development, and conduct of targeted systematic reviews. These systematic reviews seek to assist the Vector Control and Insecticide Resistance Unit of the World Health Organization's Global Malaria Programme by informing recommendation development by their Guidelines Development Group. Introduction: Malaria contributes substantially to the global burden of disease, with an estimated 247 million cases and 619,000 deaths in 2021. Vector-control is key in reducing malaria transmission. Vector-control interventions directly target the mosquito, reducing the potential for parasite infections. These interventions commonly include insecticides used in indoor residual spraying or insecticide-treated nets and larval source management. Several new vector-control interventions are under evaluation to complement these. In addition to estimating the effects of interventions on health outcomes, it is critical to understand how populations at risk of malaria consider them in terms of their feasibility, acceptability, and values. Inclusion Criteria: Eligible studies will have assessed the contextual factors of feasibility or acceptability of the interventions of interest, or the valuation of the outcomes of interests. These assessments will be from the perspective of people who receive (residents) or deliver (workers or technicians) the vector-control intervention for the purpose of preventing malaria. Methods: We will conduct this scoping review in accordance with the JBI methodology for scoping reviews and report in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews (PRISMA-ScR). We will construct the evidence and gap map following guidance from the Campbell Collaboration.

Assessing the efficacy of a brief universal family skills programme on child behaviour and family functioning in Gilgit-Baltistan, Pakistan: protocol for a feasibility randomised controlled trial of the Strong Families programme.

PURPOSE: The global burden of mental health difficulties among children underscores the importance of early prevention. This study aims to assess the efficacy, feasibility and acceptability of the Strong Families programme in enhancing child behaviour and family functioning in low-resource settings in Gilgit-Baltistan, Pakistan. METHODS AND ANALYSIS: This is a two-arm, multisite feasibility randomised controlled trial with an embedded process evaluation in three districts of Gilgit-Baltistan, namely Gilgit, Hunza and Skardu. 90 families living in these challenged settings, comprising a female primary caregiver aged 18 or above, and at least one child aged 8-15 years, will participate. Participants will be randomly assigned to either receive the Strong Families programme or to the waitlist group. Strong Families is a 7-hour family skills group intervention programme attended by children and their primary caregivers over 3 weeks. The waitlist group will be offered the intervention after their outcome assessment. Three raters will conduct blind assessments at baseline, 2 and 6 weeks postintervention. The primary outcome measures include the feasibility of Strong Families, as determined by families' recruitment and attendance rates, and programme completeness (mean number of sessions attended, attrition rates). The secondary outcomes include assessment of child behaviour, parenting practices, parental adjustment and child resilience. Purposefully selected participants, including up to five caregivers from each site, researchers and facilitators delivering the intervention, will be interviewed. Descriptive statistics will be used to analyse primary and secondary outcomes. The process evaluation will be conducted in terms of programme context, reach, fidelity, dose delivered and received, implementation, and recruitment. ETHICS AND DISSEMINATION: This study has been approved by the UNODC Drug Prevention and Health Branch in the Headquarters office of Vienna and the National Bioethics Committee of Pakistan. Findings will be disseminated through publication in reputable journals, newsletters and presentations at conferences. TRIAL REGISTRATION NUMBER: NCT05933850.

Textured insoles may improve some gross motor balance measures but not endurance measures in children with motor coordination issues. A randomised controlled feasibility trial.

BACKGROUND: Motor coordination concerns are estimated to affect 5%-6% of school-aged children. Motor coordination concerns have variable impact on children's lives, with gait and balance often affected. Textured insoles have demonstrated positive impact on balance and gait in adults with motor coordination disorders related to disease or the ageing process. The efficacy of textured insoles in children is unknown. Our primary aim was to identify the feasibility of conducting a randomised controlled trial involving children with motor control issues. The secondary aim was to identify the limited efficacy of textured insoles on gross motor assessment balance domains and endurance in children with movement difficulties. METHODS: An assessor-blinded, randomised feasibility study. We advertised for children between the ages of 5-12 years, with an existing diagnosis or developmental coordination disorder or gross motor skill levels assessed as 15th percentile or below on a norm-referenced, reliable and validated scale across two cities within Australia. We randomly allocated children to shoes only or shoes and textured insoles. We collected data across six feasibility domains; demand (recruitment), acceptability (via interview) implementation (adherence), practicality (via interview and adverse events), adaptation (via interview) and limited efficacy testing (6-min walk test and balance domain of Movement ABC-2 at baseline and 4 weeks). RESULTS: There were 15 children randomised into two groups (eight received shoes alone, seven received shoes and textured insoles). We experienced moderate demand, with 46 potential participants. The insoles were acceptable, however, some parents reported footwear fixture issues requiring modification. The 6-min walk test was described as problematic for children, despite all but one child completing. Social factors impacted adherence and footwear wear time in both groups. Families reported appointment locations and parking impacting practicality. Underpowered, non-significant small to moderate effect sizes were observed for different outcome measures. Improvement in balance measures favoured the shoe and insole group, while gait velocity increase favoured the shoe only group. CONCLUSION: Our research indicates that this trial design is feasible with modifications such as recruiting with a larger multi-disciplinary organisation, providing velcro shoe fixtures and using a shorter timed walk test. Furthermore, progressing to a larger well-powered randomised control trial is justified considering our preliminary, albeit underpowered, efficacy findings. TRIAL REGISTRATION: This trial was retrospectively registered with the Australian and New Zealand Clinical Trial Registration: ACTRN12624000160538.

Improving assay feasibility and biocompatibility of 3D cyclic olefin copolymer microwells by superhydrophilic modification via ultrasonic spray deposition of polyvinyl alcohol.

Sample partitioning is a crucial step towards digitization of biological assays on polymer microfluidic platforms. However, effective liquid filling into microwells and long-term hydrophilicity remain a challenge in polymeric microfluidic devices, impeding the applicability in diagnostic and cell culture studies. To overcome this, a method to produce permanent superhydrophilic 3-dimensional microwells using cyclic olefin copolymer (COC) microfluidic chips is presented. The COC substrate is oxidized using UV treatment followed by ultrasonic spray coating of polyvinyl alcohol solution, offering uniform and long-term coating of high-aspect ratio microfeatures. The coated COC surfaces are UV-cured before bonding with a hydrophobic pressure-sensitive adhesive to drive selective filling into the wells. The surface hydrophilicity achieved using this method remains unchanged (water contact angle of 9°) for up to 6 months and the modified surface is characterized for physical (contact angle & surface energy, morphology, integrity of microfeatures and roughness), chemical composition (FTIR, Raman spectroscopy) and coating stability (pH, temperature, time). To establish the feasibility of the modified surface in biological applications, PVA-coated COC microfluidic chips are tested for DNA sensing (digital LAMP detection of CMV), and biocompatibility through protein adsorption and cell culture studies (cell adhesion, viability, and metabolic activity). Kidney and breast cells remained viable for the duration of testing (7 days) on this modified surface, and the coating did not affect the protein content, morphology or quality of the cultured cells. The ultrasonic spray coated system, coating with 0.25 % PVA for 15 cycles with 0.12 A current after UV oxidation, increased the surface energy of the COC (naturally hydrophobic) from 22.04 to 112.89 mJ/m2 and improved the filling efficiency from 40 % (native untreated COC) to 94 % in the microwells without interfering with the biocompatibility of the surface, proving to be an efficient, high-throughput and scalable method of microfluidic surface treatment for diagnostic and cell growth applications.

Vincristine exposure in Kenyan children with cancer: CHAPATI feasibility study.

The low incidence of vincristine-induced peripheral neuropathy (VIPN) in Kenyan children may result from low vincristine exposure. We studied vincristine exposure in Kenyan children and dose-escalated in case of low vincristine exposure (NCT05844670). Average vincristine exposure was high. Individual vincristine exposure was assessed with a previously developed nomogram. A 20% dose increase was recommended for participants with low exposure and no VIPN, hyperbilirubinemia, or malnutrition. None of the 15 participants developed VIPN. Low vincristine exposure was seen in one participant: a dose increase was implemented without side effects. In conclusion, the participants did not develop VIPN despite having high vincristine exposure.

Multiparametric myocardial mapping using cardiac magnetic resonance imaging in healthy dogs: Reproducibility, repeatability, and differences across slices, segments, and sequences.

Myocardial mapping in humans has been widely studied and applied to understand heart disease, facilitate early diagnosis, and determine therapeutic targets; however, the reproducibility, repeatability, and protocol-dependent differences in myocardial mapping in dogs remain unknown, which limits its application in dogs. This study investigated the reproducibility and test-retest repeatability of myocardial mapping in dogs and evaluated the differences according to slice, segment, and sequence. Precontrast T1 (native T1), T2 (T2), and T2* relaxation time (T2*), and extracellular volume (ECV) were measured at the base, midventricle, and apex of the left ventricle in six healthy beagles. To compare the sequences, the saturation recovery-based (SMART1) and inversion recovery-based (MOLLI) sequences were used for native T1 and ECV mapping. The intraclass correlation coefficient was measured to evaluate reproducibility and repeatability using the coefficient of variation and Bland-Altman analysis. All parameters showed good to excellent intra- and interobserver reproducibility and test-retest repeatability. The apex slice showed the lowest repeatability among the slices, whereas ECV had the lowest repeatability among the parameters. Native T1, ECV, and T2* did not differ according to slice, but T2 significantly increased from the base to the apex. Native T1 was significantly higher in SMART1 than in MOLLI, whereas ECV did not differ between the two sequences. Our results suggest that myocardial mapping is applicable in dogs with high reproducibility and repeatability, although slice and sequence differences should be considered. This study can serve as a guide for myocardial mapping studies in dogs with heart disease.

Applying the multiphase optimization strategy to evaluate the feasibility and effectiveness of an online road safety education intervention for children and parents: a pilot study.

BACKGROUND: Reports of children's engagement in active transportation outline low participation rates in many countries despite many associated mental, physical, and social health benefits. One of the main contributors to this phenomenon is a cited lack of education and knowledge among children regarding active travel (AT), specifically road safety. To address this issue, the aim of this study was to evaluate the feasibility and effectiveness of an online road safety education intervention to promote AT among children and their parents. METHODS: Applying the Multiphase Optimization Strategy (MOST) for intervention development, implementation, and evaluation, we designed and assessed a four-module online road safety education intervention with a sample of 57 parent-child dyads using a 23 factorial design featuring both qualitative and quantitative analyses. RESULTS: Main intervention feasibility findings include positive and critical feedback on the program's content and design, and moderate participant engagement as reflected by program retention and completion rates. With respect to the preliminary intervention effectiveness on children, a significant improvement in road safety knowledge scores was observed for groups that feature the "wheeling safety and skills" module. Slight improvements in AT knowledge scores across all the intervention groups were observed, but were not of significance. Preliminary intervention effectiveness on select parental AT practices and perceptions saw significant improvements in some groups. Groups that featured the 'wheeling safety and skills' module exhibited significantly higher guided choice scores upon completion of the program than those who did not receive this component. CONCLUSION: The MOST framework allowed us to design and evaluate the feasibility and preliminary effectiveness of an online road safety education intervention. The developed intervention has demonstrated that it has the potential to improve children's road safety knowledge and some areas of parental AT practices and perceptions, to which improvements may be attributed to the inclusion of the "wheeling safety and skills" module, suggesting that the targeted focus on cycling skills is a prioritized area. AT programming and practice implications are discussed. Future research is encouraged to refine modules to better reflect the priorities of children and parents and to test these refined components among larger samples. WORD COUNT: 9,391 (excludes abstract, tables, figures, abbreviations, and references).

Chronic electrical stimulation with a peripheral suprachoroidal retinal implant: a preclinical safety study of neuroprotective stimulation.

Purpose: Extraocular electrical stimulation is known to provide neuroprotection for retinal cells in retinal and optic nerve diseases. Currently, the treatment approach requires patients to set up extraocular electrodes and stimulate potentially weekly due to the lack of an implantable stimulation device. Hence, a minimally-invasive implant was developed to provide chronic electrical stimulation to the retina, potentially improving patient compliance for long-term use. The aim of the present study was to determine the surgical and stimulation safety of this novel device designed for neuroprotective stimulation. Methods: Eight normally sighted adult feline subjects were monocularly implanted in the suprachoroidal space in the peripheral retina for 9-39 weeks. Charge balanced, biphasic, current pulses (100 µA, 500 µs pulse width and 50 pulses/s) were delivered continuously to platinum electrodes for 3-34 weeks. Electrode impedances were measured hourly. Retinal structure and function were assessed at 1-, 2-, 4-, 6- and 8-month using electroretinography, optical coherence tomography and fundus photography. Retina and fibrotic thickness were measured from histological sections. Randomized, blinded histopathological assessments of stimulated and non-stimulated retina were performed. Results: All subjects tolerated the surgical and stimulation procedure with no evidence of discomfort or unexpected adverse outcomes. The device position was stable after a post-surgery settling period. Median electrode impedance remained within a consistent range (5-10 kΩ) over time. There was no change in retinal thickness or function relative to baseline and fellow eyes. Fibrotic capsule thickness was equivalent between stimulated and non-stimulated tissue and helps to hold the device in place. There was no scarring, insertion trauma, necrosis, retinal damage or fibroblastic response in any retinal samples from implanted eyes, whilst 19% had a minimal histiocytic response, 19% had minimal to mild acute inflammation and 28% had minimal to mild chronic inflammation. Conclusion: Chronic suprathreshold electrical stimulation of the retina using a minimally invasive device evoked a mild tissue response and no adverse clinical findings. Peripheral suprachoroidal electrical stimulation with an implanted device could potentially be an alternative approach to transcorneal electrical stimulation for delivering neuroprotective stimulation.

A Feasibility Study on Re-establishing the Bioavailability/Bioequivalence Unit of the Department of Pharmacology and Toxicology, College of Medicine-University of the Philippines Manila.

Objectives: The Bioavailability/Bioequivalence Unit (BA/BE Unit) of the Department of Pharmacology and Toxicology, College of Medicine, University of the Philippines Manila which has not been operational since 2012, is due for renewal of its accreditation. To date, there are only three Philippine Food and Drug Administration-accredited laboratories that perform bioequivalence studies in the Philippines. One of the prerequisites of registering specific generic medicines is the conduct of Bioequivalence (BE) studies which are performed to ensure that the generic drug is at par with the innovator drug. Thus, this study aimed to determine the feasibility of re-establishing the BA/BE Unit as a bioequivalence testing center. Methods: The feasibility study done is a qualitative descriptive analysis based on expansive literature review and performance of SWOT analysis within the BA/BE unit. Literatures were selected based on its assessed relevance to the study. The databases checked were PubMed and Google Scholar. The terms used were from the Medical Subject Heading (MeSH) including feasibility studies, therapeutic equivalency, and generic drugs. Literature review was performed on the factors affecting the four types of feasibility studies (market, technical, financial, and organizational). A SWOT analysis of the BA/BE Unit was done through the review of records and documents of previous BE studies and focus group discussion among the BA/BE Unit team members. Results: The BA/BE Unit conducted 24 bioequivalence studies from 2006-2009 and still receives inquiries from drug companies. It implements its QMS throughout the pre-analytical, analytical, and post-analytical stages of the workflow. Its organizational structure consists of qualified professionals with updated GCP and GLP certificates. Because of the adequately equipped facility, lower honoraria for government-employed personnel, and lower expenses for laboratories and in-patient admissions, the cost of conducting a bioequivalence study in the BA/BE Unit will be lower than in other BE centers. Conclusion: Based on the SWOT analysis and market, technical, financial, and organizational considerations, re-establishing the BA/BE Unit as a bioequivalence testing center is feasible.

The Feasibility and Acceptability of Sharing Video Recordings of Amyotrophic Lateral Sclerosis Clinical Encounters With Patients and Their Caregivers: Pilot Randomized Clinical Trial.

BACKGROUND: Multidisciplinary clinics (MDCs) provide benefits to patients with amyotrophic lateral sclerosis (ALS) and their caregivers, but MDC visits are information-heavy and can last 4 hours, with patients and caregivers meeting with multiple specialists within each MDC visit. There are questions about the effectiveness of current methods of sharing information from MDCs with patients. Video recordings are a promising new method of sharing information that may allow patients and caregivers to revisit the MDC and remind them of clinical recommendations and conversations. OBJECTIVE: The objective of this trial is to determine the feasibility and acceptability of sharing information through video recordings of ALS MDC visits with patients and caregivers. METHODS: This study was a randomized, controlled pilot trial with 3 months of follow-up from April 2021 to March 2022 in a rural multidisciplinary neurology clinic. We recruited patients with ALS, their caregivers, and their clinicians. Patients and their caregivers were randomized to either receive their normal after-visit summary (treatment as usual) or to receive their normal after-visit summary and a video recording of their MDC visit (video). Each specialist visit had its own recording and was accessible by patients and caregivers using a secure web-based platform called HealthPAL over a 3-month follow-up period. Primary study outcomes were feasibility and acceptability of the video intervention measured by recruitment rate (target: 70%), percentage of participants watching videos (target: 75%), and the Feasibility of Intervention Measure and Acceptability of Intervention Measure (targets: 3/5). We hypothesized that video recording would be feasible and acceptable to patients and their caregivers. RESULTS: Of the 30 patients approached, 24 were recruited, while all caregivers (n=21) and clinicians (n=34) approached were recruited. A total of 144 specialist visits were recorded, approximately 12 specialist visits at a median of one MDC visit per patient. Of the recorded patients, 75% (9/12) viewed videos. High median intervention feasibility (4, SD 0.99) and acceptability (4, SD 1.22) of intervention measures were reported by patients and caregivers in the intervention arm. High median intervention feasibility (5, SD 0.21) and acceptability (4.88, SD 0.4) were reported by clinicians. Of the 24 patients, 50% (n=12) did not complete a 3-month follow-up, primarily due to death (n=10). CONCLUSIONS: Video recording is highly feasible and acceptable for patients, caregivers, and clinicians at a rural ALS clinic. Our level of attrition is a useful benchmark for future studies in MDC populations. Despite high rates of patient death, 1-week assessments highlight the value of recordings for both patients and caregivers. TRIAL REGISTRATION: ClinicalTrials.gov NCT04719403; https://clinicaltrials.gov/study/NCT04719403.

First Clinical Safety and Feasibility Data of Whole-body Hyperthermia Pressurized Intraperitoneal Aerosol Chemotherapy (WBH-PIPAC) for Peritoneal Surface Malignancies.

BACKGROUND/AIM: This study evaluated the feasibility and safety of whole-body hyperthermia pressurized intraperitoneal aerosol chemotherapy (WBH-PIPAC) in patients with peritoneal surface malignancies. PATIENTS AND METHODS: This study retrospectively analyzed a database of 28 patients who had received one cycle of normothermic PIPAC prior to repetitive WBH-PIPACs. WBH (39-40°C) was induced using a Water-filtered infrared A device. Doxorubicin plus cisplatin or oxaliplatin was nebulized into a constant capnoperitoneum of 20 mmHg for 30 min at doses of 6.0 mg, 30.0 mg, or 120 mg per m2 body surface area, respectively. The primary outcome measures were feasibility and perioperative complications. RESULTS: The median age was 62 years (range=45-78 years). Primary tumor sites included the upper gastrointestinal tract (n=9), colon/rectum (n=7), hepato-pancreato-biliary system (n=3), peritoneum (n=2), ovaries (n=2), and unknown primary (n=5). The induction of WBH failed in one patient (6 liters ascites). After a median warming period of 95 min (53-117 min), the median rectal temperature (Trec) was 39.5°C (39.2-39.9°C). No hyperthermia-related side effects were observed. Twenty-seven patients received 50 WBH-PIPACs. The median time of therapeutic capnoperitoneum and treatment time with Trec ≥39°C was 39 min (37-43 min) and 66 min (53-69 min), respectively. The overall rate of postoperative procedure-related complications was 9/50, including seven grade I and two grade II complications. There were no grade III-V complications. CONCLUSION: In a highly selected group of patients, the feasibility and perioperative safety of WBH-PIPAC was comparable to normothermic PIPAC.

Preoperative radiosurgery for brain metastases (PREOP-1): A feasibility trial.

Purpose: Preoperative radiosurgery (SRS) of brain metastases (BM) aims to achieve cavity local control with a reduction in leptomeningeal relapse (LMD) and without additional radionecrosis compared to postoperative SRS. We present the final results of a prospective feasibility trial of linac-based stereotactic radiosurgery (SRS) prior to neurosurgical resection of a brain metastasis (PREOP-1). Methods: Eligibility criteria included a BM up to 4 cm in diameter for elective resection. The primary endpoint was the feasibility of delivering linac-based preoperative SRS in all patients prior to anticipated gross tumour resection. Secondary endpoints included rates of LMD, local control and overall survival. Exploratory endpoints were the level of expression of immunological and proliferative markers. Results: Thirteen patients of median age 65 years (range 41-77) were recruited. Twelve patients (92 %) received preoperative radiosurgery and metastasectomy and one patient went directly to surgery and received postoperative SRS, thus the primary endpoint was not met. The median time between referral and preoperative SRS was 6.5 working days (1-10) and from SRS to neurosurgery was 1 day (0-5). The median prescribed dose was 16 Gy (14-19) to a median planning target volume of 12.7 cm3 (5.9-26.1). Five patients completed 12-month follow-up after preoperative SRS without local recurrence or leptomeningeal disease. The patient who received postoperative FSRT developed LMD after six months. There was one transient toxicity (grade 2 alopecia) and nine patients have died from extracranial causes. Patients reported significant improvement in motor weakness at 6 months (P = 0.04). No pattern in changes of marker expression was observed. Conclusion: In patients with large brain metastasis without raised intracranial pressure, linac-based preoperative SRS was feasible in 12/13 patients and safe in 12/12 patients without any surgical delay or intracranial complications.

Assessment of the Feasibility of Objective Parameters as Primary End Points for Patients Affected by Knee Osteoarthritis: Protocol for a Pilot, Open Noncontrolled Trial (:SMILE:).

BACKGROUND: Osteoarthritis (OA) is a disabling condition that affects more than one-third of people older than 65 years. Currently, 80% of these patients report movement limitations, 20% are unable to perform major activities of daily living, and approximately 11% require personal care. In 2014, the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) recommended, as the first step in the pharmacological treatment of knee osteoarthritis, a background therapy with chronic symptomatic slow-acting osteoarthritic drugs such as glucosamine sulfate, chondroitin sulfate, and hyaluronic acid. The latter has been extensively evaluated in clinical trials as intra-articular and oral administration. Recent reviews have shown that studies on oral hyaluronic acid generally measure symptoms using only subjective parameters, such as visual analog scales or quality of life questionnaires. As a result, objective measures are lacking, and data validity is generally impaired. OBJECTIVE: The main goal of this pilot study with oral hyaluronic acid is to evaluate the feasibility of using objective tools as outcomes to evaluate improvements in knee mobility. We propose ultrasound and range of motion measurements with a goniometer that could objectively correlate changes in joint mobility with pain reduction, as assessed by the visual analog scale. The secondary objective is to collect data to estimate the time and budget for the main double-blind study randomized trial. These data may be quantitative (such as enrollment rate per month, number of screening failures, and new potential outcomes) and qualitative (such as site logistical issues, patient reluctance to enroll, and interpersonal difficulties for investigators). METHODS: This open-label pilot and feasibility study is conducted in an orthopedic clinic (Timisoara, Romania). The study includes male and female participants, aged 50-70 years, who have been diagnosed with symptomatic knee OA and have experienced mild joint discomfort for at least 6 months. Eight patients must be enrolled and treated with Syalox 300 Plus (River Pharma) for 8 weeks. It is a dietary supplement containing high-molecular-weight hyaluronic acid, which has already been marketed in several European countries. Assessments are made at the baseline and final visits. RESULTS: Recruitment and treatment of the 8 patients began on February 15, 2018, and was completed on May 25, 2018. Data analysis was planned to be completed by the end of 2018. The study was funded in February 2019. We expect the results to be published in a peer-reviewed clinical journal in the last quarter of 2024. CONCLUSIONS: The data from this pilot study will be used to assess the feasibility of a future randomized clinical trial in OA. In particular, the planned outcomes (eg, ultrasound and range of motion), safety, and quantitative and qualitative data must be evaluated to estimate in advance the time and budget required for the future main study. Finally, the pilot study should provide preliminary information on the efficacy of the investigational product. TRIAL REGISTRATION: ClinicalTrials.gov NCT03421054; https://clinicaltrials.gov/study/NCT03421054. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/13642.