Pilot Study Research Articles

Aripiprazole/Sertraline Combination: Clinical and Cost-Effectiveness in Comparison With Quetiapine for the Treatment of Bipolar Depression (ASCEnD Trial)-Protocol for a Nested Qualitative Study.

Bipolar disorder is a recurrent mental health disorder with a prevalence rate of 1.4%. On average, there can be a delay of 9.5 years from the initial presentation of symptoms to a confirmed diagnosis. Individuals living with bipolar disorder have a reduced life expectancy. There is limited evidence regarding the effectiveness of antidepressants in treating bipolar disorder. The ASCEnD clinical trial will test the clinical and cost-effectiveness of the aripiprazole/sertraline combination in comparison with quetiapine for the treatment of bipolar depression (individuals who suffer from depressive episodes in bipolar disorder) and will include a nested qualitative study. The qualitative study will use semi-structured interviews to explore pilot trial participants' and clinicians' perspectives on recruitment procedures, the acceptability of the intervention, the management of bipolar disorder and attitudes to medication combinations. Findings will inform recruitment strategies and optimise training for the participating sites in the ASCEnD full trial. They will also help to illuminate the lived experience of people with bipolar disorder and the clinicians who work with people with bipolar disorder. The discussion will explore perspectives on the delay in diagnosis, having a diagnosis, the impact of living with bipolar disorder and attitudes to treatment, including drug combinations. A Lived Experience Advisory Panel (LEAP) has been convened with the support of the McPin Foundation, which will contribute to the ASCEnD trial and its nested qualitative study to provide input on the design and delivery of the trial and qualitative study, analysis of qualitative data and dissemination of findings.

Physical activity and symmetry following total knee arthroplasty: Results of a pilot randomized trial

ObjectiveThis pilot trial examined a Physical Activity and Symmetry (PAS) intervention focused on common deficits of physical inactivity and joint loading asymmetry following total knee arthroplasty (TKA). DesignParticipants (n ​= ​60) were enrolled during routine physical therapy (PT) following TKA and randomized to the PAS intervention or an attention (ATT) control group. The PAS intervention included physical activity counseling and balance exercise to address joint loading symmetry; content was delivered during 2 sessions at the end of routine PT plus supplemental sessions 4-weeks and 8-weeks following PT. The ATT control condition included supplemental sessions at 4-weeks and 8-weeks focused on general evaluation of surgical recovery benchmarks. Primary outcomes were weekly minutes of moderate to vigorous physical activity (MVPA), measured with an accelerometer, and peak force loading symmetry (limb symmetry index; LSI) during a 10 ​m walk, measured with a 3-sensor in-shoe device. General linear mixed models compared changes in outcomes between randomized groups at 3-month and 6-month follow-up. ResultsBoth PAS and ATT groups increased MVPA, but there were no clinically meaningful between-group differences at 3- or 6-month follow-up (p ​> ​0.05). There were also no clinically meaningful between-group differences LSI at 3- or 6-month follow-up (p ​> ​0.05). ConclusionThe PAS intervention did not yield improvements beyond ATT control. It is possible that PAS components were being delivered as part of routine PT, and a more intensive intervention (e.g., more visits, guidance for exercise progression) or targeted approach (e.g., those with deficits at end of routine care) may be needed to further improve outcomes.

Pilot feasibility randomised controlled trial of cognitive–behavioural therapy for functional cognitive disorder after concussion

BackgroundFunctional cognitive disorder (FCD) may be common after a concussion, and no evidence-based treatment options are available. The current study evaluated the feasibility of a novel cognitive–behavioural therapy (CBT) protocol...

Albumin adjuvant therapy for acute ischemic stroke with large vessel occlusion (AMASS-LVO): rationale, design, and protocol for a phase 1, open-label, clinical trial.

Acute ischemic stroke (AIS) is an acute brain injury caused by sudden occlusion of a blood vessel. Endovascular therapy is the most effective way to restore blood flow. However, despite the restoration of blood flow in some patients, their clinical prognosis often remains unsatisfactory. Albumin has shown neuroprotective effects in animal models of AIS. Therefore, this study aims to evaluate the safety, feasibility, and efficacy of local arterial infusions of 20% human serum albumin solution as an adjuvant therapy after endovascular therapy in patients with AIS. This study is a prospective, therapeutic exploratory, non-randomized, open-label, phase 1 clinical trial testing the use of 20% human serum albumin solution injected via the artery immediately after successful reperfusion in patients with AIS. The study is divided into two stages. In the first stage, a single-dose-finding will explore the maximum safe dose according to the 3 + 3 dose escalation principle;, with the maximum dose being 0.60 g/kg. After recanalizing the occluded blood vessel, human serum albumin solution will be injected into the internal carotid artery region through a guiding catheter for 30 min. The second stage involves an albumin adjuvant therapy cohort (AT) and an endovascular treatment lonely cohort (ET). The AT cohort will encompass at least 15 additional participants to complete safety trials at the maximum safe dose determined in the first stage. The ET cohort will include well-matched patients receiving endovascular therapy alone, derived from a contemporaneous prospective registry, who will be excluded from having cardiopulmonary disorders and from receiving any neuroprotective therapy. The primary outcome of this study will be symptomatic intracranial hemorrhage. Efficacy outcomes will include the proportion of patients with the progression of cerebral infarction volume, a modified Rankin Scale of 0-2 on day 90 after randomization. An exploratory secondary outcome will be the analysis of thromboinflammatory and neuroprotective molecule profiles. This pilot trial aims to explore the safety and efficacy of arterial infusion of an albumin solution after occlusive vessel opening in AIS. The results will provide data parameters for subsequent tests on the arterial infusion of albumin solutions. ClinicalTrials.gov, NCT05953623.

Investigating Transcutaneous Vagus Nerve Stimulation in Amnestic Mild Cognitive Impairment

Abstract Background New treatments are urgently needed for individuals with Mild Cognitive Impairment (MCI) - in particular for those with amnestic MCI, of whom a high proportion have underlying Alzheimer's Disease (AD). Transcutaneous Vagus Nerve Stimulation (tVNS) is a non-invasive neuro-modulatory treatment which has not been extensively examined in older adults with amnestic MCI. Methods A single site, single-blind, randomised three-arm crossover pilot trial of acute (60 minutes) tVNS (baseline, sham or active stimulation) was conducted a Regional Specialist Memory Service. Forty participants (age 71.7 ±6.9; 22/40 male) with diagnosed amnestic MCI were recruited. Given the links between AD and neuro-cardiovascular instability, potential adverse effects of active tVNS were assessed using beat-to-beat peripheral (Blood Pressure (BP) and Heart Rate [HR]) and central (via Near Infra-red Spectroscopy) haemodynamic responses to Active Stand (AS). Cognition was assessed between 21.3 ±4.9 and 60.5 ±4.4 minutes using a domain-specific cognitive performance battery with results analysed using mixed-effects linear regression. Results In older adults with amnestic MCI, tVNS was safe, tolerable and acceptable with 98% of participants stating they would use the device again. There was no significant effect on BP, or HR responses to AS and cerebral oxygenation remained stable during AS. After tVNS stimulation, performance on tests of spatial navigation were significantly improved compared to both baseline (ß= -8.76; [-14.91, -2.56]; p=0.01) and sham (ß= -4.15; [-7.32, -0.99]; p=0.01) conditions. Conclusion tVNS is a safe and tolerable treatment modality in older adults with amnestic MCI. Future studies should explore sustained effects and feasibility of domiciliary use.

Mindfulness to enhance quality of life and support advance care planning: a pilot randomized controlled trial for adults with advanced cancer and their family caregivers

BackgroundPatients with advanced cancer and family caregivers often use avoidant coping strategies, such as delaying advance care planning discussions, which contribute to deterioration in their quality of life. Mindfulness-based interventions have shown promise in improving quality of life in this population but have rarely been applied to advance care planning. This pilot trial examined the preliminary efficacy of a group-based Mindfulness to Enhance Quality of Life and Support Advance Care Planning (MEANING) intervention for patient-caregiver dyads coping with advanced cancer. Primary outcomes were patient and caregiver quality of life or well-being, and secondary outcomes included patient advanced care planning engagement (self-efficacy and readiness) and other psychological and symptom outcomes.MethodsIn this pilot trial, dyads coping with advanced cancer were recruited from five oncology clinics in the midwestern U.S. and randomized to six weekly group sessions of a mindfulness intervention (n = 33 dyads) or usual care (n = 22 dyads). Outcomes were assessed via surveys at baseline, post-intervention, and 1 month post-intervention. All available data were included in the multilevel models assessing intervention efficacy.ResultsPatients in the MEANING condition experienced significant increases in existential well-being and self-efficacy for advance care planning across follow-ups, whereas usual care patients did not. Other group differences in outcomes were not statistically significant. These outcomes included other facets of patient well-being, caregiver quality of life, patient readiness for advance care planning, caregiver burden, and patient and caregiver depressive symptoms, anxiety, sleep disturbance, cognitive avoidance, and peaceful acceptance of cancer. However, only MEANING patients showed moderate increases in psychological well-being across follow-ups, and MEANING caregivers showed moderate increases in quality of life at 1-month follow-up. Certain psychological outcomes, such as caregiver burden at 1-month follow-up, also showed moderate improvement in the MEANING condition. Patients in both conditions reported small to moderate increases in readiness to engage in advance care planning.ConclusionsA mindfulness-based intervention showed promise in improving quality-of-life and advance care planning outcomes in patients and caregivers coping with advanced cancer and warrants further testing.Trial RegistrationClinicalTrials.gov NCT03257007. Registered 22 August 2017, https://clinicaltrials.gov/ct2/show/NCT03257007.

Transcutaneous Electrical Acupoint Stimulation for Elders with Amnestic Mild Cognitive Impairment: A Randomized Controlled Pilot and Feasibility Trial

Background: Amnestic mild cognitive impairment (aMCI) is an important window of opportunity for early intervention and rehabilitation in dementia. The aim of this study was to investigate the feasibility and effect of delivering transcutaneous electrical acupuncture stimulation (TEAS) intervention to elders with aMCI. Methods: A total of 61 aMCI patients were randomly allocated into the intervention group (receiving a 12-week TEAS) and control group (receiving health education). The feasibility outcomes included recruitment rate, retention rate, adherence rate, and an exploration of patients’ views and suggestions on the research. The effective outcomes included cognitive function, sleep quality, and life quality, which were measured by the Montreal cognitive assessment scale (MoCA), auditory verbal learning test—Huashan version (AVLT-H), Pittsburgh sleep quality index (PSQI), and quality of life short-term-12 (QoL SF-12). Results: The recruitment rate, retention rate, and adherence rate were 67.35%, 92.42%, and 85.29%, respectively. Most aspects of the research design and administration of the TEAS intervention were acceptable. The quantitative analysis suggests that compared with the control group, the scores of MoCA, AVLT-H, and SF-12 (mental component summary) were significantly better (p < 0.05); however, the differences were not statistically significant in PSQI and SF-12 (physical component summary) (p > 0.05). Conclusions: The findings demonstrated that the study was feasible. TEAS awas possible for enhancing cognitive function and mental health in people with aMCI.

Cone Beam Computed Tomography-Guided Navigation Bronchoscopy with Augmented Fluoroscopy for the Diagnosis of Peripheral Pulmonary Nodules: A Step-by-Step Guide.

Cone beam computed tomography-guided navigation bronchoscopy (CBCT-NB) with augmented fluoroscopy (AF) guidance represents a minimally invasive endobronchial technique for diagnosing small, peripheral pulmonary lesions. This approach is characterized by its high diagnostic accuracy and low complication risk. Current pilot trials are exploring the application of localized therapies using this innovative approach. This report aims to provide a detailed procedural guide for performing CBCT-NB with AF guidance as the only tool for navigation and image guided biopsy. We outline the procedural steps involved in the CBCT-NB procedure for diagnosing peripheral pulmonary lesions, supported by specific intra-procedural clinical video footage. The steps include (1) preprocedural considerations, (2) a detailed procedural workflow encompassing navigation to the target lesion, (3) position confirmation and tissue acquisition, and (4) postprocedural follow-up. CBCT-NB with AF guidance is a safe and precise stand-alone navigation modality that offers high-resolution real-time 3D imaging, enhancing the diagnosis and potential treatment of peripheral pulmonary nodules.

Feasibility of a person-centred multidimensional interdisciplinary rehabilitation programme in community-dwelling people with dementia: a randomised controlled pilot trial

BackgroundA team-based, individualised rehabilitation approach may be required to meet the complex needs of people with dementia. This randomised controlled pilot trial evaluated the feasibility of a person-centred multidimensional interdisciplinary rehabilitation programme for community-dwelling older people with dementia and their informal primary caregivers.MethodsParticipants with dementia were randomised to an intervention group (n = 31, mean age (SD) 78.4 (6.0) years) or usual care (n = 30, mean age 79.0 (7.1)). The rehabilitation programme consisted of a 20-week rehabilitation period containing assessments and interventions based on each individual’s goals, and group-based physical exercise plus social interaction twice a week for 16 weeks at a rehabilitation unit. After 5 and 14 months, the interdisciplinary team followed up participants over two four-week periods. For both groups, dates of deaths and decision to move to nursing home over three years, as well as interventions for the relevant periods, were collected. Blinded assessors measured physical functions, physical activity, activities of daily living, cognitive functions, nutritional status, and neuropsychiatric symptoms at baseline and at 5, 12, 24, and 36 months.ResultsParticipants in the intervention group received a mean of 70.7 (20.1) interventions during the 20-week rehabilitation period, delivered by all ten team professions. The corresponding figures for the control group were 5.8 (5.9). In the intervention group, all but one participated in rehabilitation planning, including goal setting, and attendance in the exercise and social interaction groups was 74.8%. None of the adverse events (n = 19) led to any manifest injury or disease. Cox proportional hazard regression showed a non-significant lower relative risk (HR = 0.620, 95% CI 0.27–1.44) in favour of the intervention for moving to nursing home or mortality during the 36-month follow-up period. Linear mixed-effect models showed non-significant but potentially clinically meaningful between-group differences in gait, physical activity, and neuropsychological symptoms in favour of the intervention.ConclusionsThe rehabilitation programme seems feasible among community-dwelling older people with dementia. The overall results merit proceeding to a future definitive randomised controlled trial, exploring effects and cost-effectiveness. One could consider to conduct the programme earlier in the course of dementia, adding cognitive training and a control attention activity.Trial registrationThe study protocol, ISRCTN59155421, was registered online 4/11/2015.

Voucher-based contingency management to promote treatment engagement in comorbid alcohol use disorder and alcohol-related liver disease: A pilot theory-informed qualitative study with service users.

Effective interventions for the management of alcohol-related liver disease (ARLD) remain a gap in clinical practice, and patients' engagement with alcohol services is suboptimal. Based upon the principles of operant conditioning, contingency management (CM) is a psychosocial intervention th at involves gradual, increasing incentives upon completion of treatment-related goals such as treatment attendance. A pilot feasibility trial was conducted with 30 adult patients recruited from an inpatient clinical setting. Consecutive sampling was used to recruit patients presenting comorbid alcohol use disorder (AUD) and ARLD. Participants were randomized to integrated liver care (ILC), receiving hepatology and AUD care, or ILC with a voucher-based CM intervention (intervention arm). A longitudinal qualitative approach was adopted to explore anticipated (Stage 1) and experienced acceptability (Stage 2). The Theoretical Framework of Acceptability (TFA) guided semi-structured in-depth interviews and deductive analysis. Thirty participants were enrolled in the pilot trial, and interviews were conducted with 24 participants at Stage 1 and seven at Stage 2. Over half of the cohort (54.2%, n = 13) presented decompensated liver disease, and an average of 179 units of alcohol were consumed per week. Overall positive views toward voucher-based CM were noted, and explanatory data emerged across five TFA domains (intervention coherence, ethicality, self-efficacy, perceived effectiveness, and affective attitude). The core aspects of the voucher-based CM intervention matched participants' preferences and needs. Participants regarded CM as having a symbolic value and strengthening the therapeutic alliance with healthcare providers. The data support the scope of voucher-based CM intervention to promote engagement with treatment services, and its potential to address the gaps in the care continuum in ARLD. The findings are of practical significance for developing person-centered, tailored interventions for this clinical population. The outcomes of this investigation can inform decision-making among stakeholders and healthcare providers and improve health outcomes for this clinical population.

The Effects of Laughter Therapy on Perceived Stress and Quality of Life in Women With Breast Cancer Receiving Chemotherapy: A Parallel-Group Randomized Controlled Pilot Trial.

Women with breast cancer experience various symptoms secondary to chemotherapy that reduce their quality of life and increase their stress levels. To evaluate the effects of laughter therapy on perceived stress levels and quality of life in women with breast cancer receiving chemotherapy using a parallel-group randomized controlled pilot trial. Forty-two women were randomly assigned to intervention and control groups. The intervention group received 40 minutes of laughter therapy twice a week for 8 weeks. The control group received routine treatment. The women in both groups completed the Perceived Stress Scale and SF-12 Health Survey at baseline, week 5, and week 9 after randomization. There was a significant decrease in the mean Perceived Stress Scale scores in the intervention group compared with those in the control group at weeks 5 and 9 compared with baseline, and the difference between groups by measurement week was significant (P < .001). Women in the intervention group had higher Physical Component Summary-12 and Mental Component Summary-12 scores in weeks 5 and 9 compared with those in the control group, and there was a significant difference between groups in terms of change in the Physical Component Summary-12 and Mental Component Summary-12 mean scores over time (P < .001). Laughter therapy is possible to use as a nursing intervention to reduce the perceived stress levels and increase the quality of life of women receiving chemotherapy for breast cancer. Nurses can apply laughter therapy in the symptom management of women receiving chemotherapy.

Exhaled Breath Condensate Surveillance for Aspergillus in Acute Leukemia—a Pilot Trial

Abstract Invasive fungal infections in patients with leukemia carry a high mortality rate, but early diagnosis has the potential to modify this natural history. A novel screening method using Aspergillus droplet-digital polymerase chain reaction in exhaled breath condensate may have a similar performance to serum galactomannan screening. Larger studies, including other molds, are necessary.

Dietary counseling plus omega-3 supplementation in the treatment of generalized anxiety disorder: results of a randomized wait-list controlled pilot trial (the ‘EASe-GAD Trial’)

ABSTRACT Objectives Clinical evidence suggests that nutrition interventions can significantly improve symptoms of major depressive disorder; however, the effect on clinical anxiety symptoms in individuals with anxiety disorders has not been studied. The primary objective of the present study was to assess the feasibility and acceptability of a nutrition intervention. The secondary objectives included assessing changes in anxiety symptom severity, diet quality, self-efficacy, mindful eating, quality of life, and biomarkers. Methods This study was a randomized, wait-list controlled pilot trial delivering a 12-week, biweekly dietary counseling intervention and omega-3 supplementation to 50 adult women with generalized anxiety disorder. Questionnaires and blood work were completed at baseline, after the waiting period, and after the intervention. Results 443 individuals expressed interest within eight months; 50 met the criteria for enrollment. The mean number of sessions attended was 6.4. Final questionnaires were completed by 46 participants. Eighty-four percent of participants strongly agreed with the statement ‘My experience during this study was positive’. The mean anxiety symptom severity score in the intervention group was 26.2 (95% CI 22.94–29.48) at baseline and 11.0 (95% CI 8.05–13.87) at week 12. The mean diet quality score was 7.2 (95% CI 6.32–8.10) and 10.5 (95% CI 9.55–11.49) at baseline and week 12, respectively. Among the waitlist participants, the mean baseline anxiety score was 29.3 (95% CI 24.73–33.91) and 26.8 (95% CI 22.09–31.56) at week 12. Discussion This study was feasible and acceptable. Participation in the intervention was associated with a decrease in anxiety symptoms. These findings lay the foundation for large-scale studies. Trial registration: ClinicalTrials.gov NCT05573672.

Involving women with limited English proficiency in group antenatal care: Findings from the integrated process evaluation of the Pregnancy Circles pilot trial

Problem In the United Kingdom, poor experiences and outcomes of antenatal care among women with limited English proficiency (LEP) are widely documented. BackgroundGroup antenatal care aims to address some limitations of traditional care by combining health assessment, information sharing and peer support, but the inclusion of women with LEP in mixed-language groups has not been explored. AimThis qualitative study used observations and interviews to explore whether linguistic diversity could be incorporated into group antenatal care (Pregnancy Circles). Women with LEP were invited to take part in mixed-language groups in a large urban NHS trust as part of the Pregnancy Circles pilot trial (ISRCTN66925258 Retrospectively registered 03 April 2017; North of Scotland Research Ethics Service 16/NS/0090). FindingsThree Pregnancy Circles including women with LEP were implemented. Linguistically integrated groups required additional resources (time, interpreters, midwifery skills). Four themes emerged: ‘Interpreting as helping’, ‘Enhanced learning’, ‘Satisfaction and belonging’ and ‘Complex lives’. DiscussionWomen with LEP accessing interpreting in Pregnancy Circles reported high levels of satisfaction, contrasting with reported experiences in traditional care. Three theories of effect emerged as relevant for women with LEP: social support.

Effects of long-term periodized carbohydrate intake on body composition, substrate metabolism and running performance in recreational active men: A pilot trial

Introduction &amp; Purpose It is important to consider the impact of nutrition on training adaptations and performance outcomes (Jeukendrup, 2017). The present study was therefore conducted with the objective of determining whether long-term periodizing carbohydrate (CHO) intake during an eight-week endurance training plan has any benefit in comparison to a traditional high-CHO or low-CHO diet in terms of running performance, substrate metabolism and body composition in recreational active males. Methods In a controlled, randomised, parallel-group and free-living design, recreationally active runners (n = 24, VO2 peak: 51 ± 8 mL·min-1·kg-1) completed 8 weeks of an ad-libitum dietary intervention (LCHF[low CHO, high fat]/CHO: 4-week regimen with ≤ 50 g CHO per day directly followed by a 4-week regimen comprising 50-60% of daily energy intake from CHO, n = 8; CHO/CHO: 8-week regimen comprising 50-60% of daily energy intake from CHO, n = 9; LCHF/LCHF: 8-week regimen with ≤ 50 g CHO per day, n = 7) together with 5 prescribed sessions of an endurance training program. Dietary recalls were conducted 3 times a week. Body composition, performance and substrate metabolism were assessed 3 times during the study (T -0, T -1 and T -2) using bioelectric impedance and a graded exercise test on a treadmill starting at 6 km·h−1 with increasing speed by 1.5 km·h−1 every 3 minutes until exhaustion. Data were analysed using a 2-way mixed ANOVA and are presented as mean ± STD. Significance was set at p &lt; 0.05. Results Peak running speed (PRS) and time to exhaustion (TTE) demonstrated an increase over time, with no additional benefit observed in relation to any group. Total fat oxidation and maximum fat oxidation (MFO) increased in the first half of the LCHF/CHO diet and decreased during the CHO rich diet (p &lt; 0.001). In LCHF/LCHF fat oxidation and MFO increased from T -0 to T -1 (p &lt; 0.001) and remained unchanged at T -2. In CHO/CHO no changes in fat oxidation or MFO were observed (p &gt; 0.05). Total fat oxidation and MFO were significantly higher at T -1 in LCHF/CHO and LCHF/LCHF compared to CHO/CHO (p &lt; 0.05). However, at T -2 fat oxidation and MFO were significantly higher in LCHF/LCHF compared to LCHF/CHO and CHO/CHO (p &lt; 0.05). Significant reductions in weight, BMI, and absolute fat mass were observed in LCHF/CHO from T -0 to T -1 (p &lt; 0.05) without any further changes until T -2. For LCHF/LCHF weight and BMI were significantly reduced in the first four weeks (p &lt; 0.001) and even further reduced in the second half (p &lt; 0.05). For CHO/CHO no significant changes in body composition were observed (p &gt; 0.05). Discussion &amp; Conclusion As previously noted, a high-fat diet resulted in a greater reliance on fat oxidation during exercise (Cao et al., 2021). Here, long-term periodisation of CHO according to the preferred training adaptation leads to changes in substrate metabolism during exercise in terms of improved fat oxidation during a LCHF diet and restoration of CHO oxidation during a CHO-rich diet. Despite the observed improvements in PRS and TTE over the course of the study, no significant advantage was demonstrated by any of the groups in comparison to the other trial groups. References Cao, J., Lei, S., Wang, X., &amp; Cheng, S. (2021). The effect of a ketogenic low-carbohydrate, high-fat diet on aerobic capacity and exercise performance in endurance athletes: A systematic review and meta-analysis. Nutrients, 13(8), Article 2896. https://doi.org/10.3390/nu13082896 Jeukendrup, A. E. (2017). Periodized nutrition for athletes. Sports Medicine, 47(S1), 51-63. https://doi.org/10.1007/s40279-017-0694-2

Acceptability of a Serious Game About Proton Radiotherapy Designed for Children Aged 5 to 14 Years and Its Potential Impact on Perceived Anxiety: Feasibility and Randomized Controlled Pilot Trial.

Children who are going to undergo radiotherapy have displayed fear and anxiety. Therefore, a web-based serious game was developed as a psychological preparation to investigate if it could affect anxiety levels. In an earlier stage, children with experience of radiotherapy had been part of the developmental process. The study aimed to investigate the feasibility in terms of reach, usability, and acceptability of a serious game about proton radiotherapy and to pilot that it did not increase anxiety levels in children aged 5 to 14 years undergoing radiotherapy. The design was a randomized controlled pilot trial with predefined feasibility criteria. In total, 28 children were assessed for eligibility, and 23 met the inclusion criteria. They were consecutively randomized into 1 of 2 study arms. One child was excluded after randomization. If randomized into arm 1, the children received the intervention before treatment started. Children in arm 2 were treated as controls. Questionnaires with fixed answers were used to assess anxiety levels (an adapted version of the State-Trait Anxiety Inventory for Children) and experiences of gameplay (an adapted version of Player Experience of Need Satisfaction [PENS]). The children were asked to answer questionnaires at 5 different measurement occasions during their radiotherapy treatment. In arm 1, age ranged from 5 to 13 (mean 8.4, SD 2.4) years. In arm 2, age ranged from 5 to 11 (mean 7.6, SD 2.3) years. The sample consisted of 15 girls and 7 boys. The feasibility criterion that the children should play the game for 20 minutes or more was not met. Mean playtime for children in arm 1 was 32.1 (SD 23.8) minutes, where 18 children had played for at least 15 minutes. The criterion that 70% (n=16) or more of the participants should return all of the questionnaires was not met; however, more than 73% (n=16) returned the PENS questionnaires. The State-Trait Anxiety Inventory for Children was returned by 73% (n=16) on day 0, 77% (n=17) on day 1, 82% (n=18) on day 3, 82% (n=18) on day 6, and 86% (n=19) on day 15. All feasibility criteria set for the study were not met, suggesting that adaptions need to be made if a future study is to be undertaken. Further, the analysis revealed that there was no indication that playing increased the children's self-reported anxiety. The PENS questionnaire adapted for children showed promising results regarding player satisfaction when using the serious game. When studying children with severe conditions and young age, 5 measurement occasions seemed to be too many. Measuring both player satisfaction or experience and knowledge transfer would be preferable in future studies.

Supplemental ambient lighting intervention to improve sleep in Parkinson's disease: A pilot trial

ImportanceSleep disturbances in Parkinson's disease (PD) are common and often adversely affect quality of life. Light therapy has benefited sleep quality and mood outcomes in various populations but results to date with conventional light therapy boxes in PD patients have been mixed. We hypothesized that a passive lighting intervention, applied in the morning and designed to maximally affect the circadian system, would improve measures of sleep and mood in PD patients. MethodsIn this single-arm, within-subjects intervention study, baseline objective sleep (actigraphy), subjective sleep quality (questionnaires), and subjective mood (questionnaires) data were collected for 1 week. Lighting was then administered to participants via table/floor lamps installed in the home or via personal light therapy glasses for 2 h in the morning, 7 days per week, over the following 4-week period. Post-intervention data for the same outcomes were collected during the final week of the intervention period. ResultsAmong 20 participants (12 women, 8 men; mean [SD] age 72.1 [9.5] years, disease duration 9.0 [5.2] years), objective sleep duration increased significantly by 28.5 min (p = 0.029) and objective sleep time increased significantly by 19.9 min (p = 0.026). ConclusionPassive and easily administered lighting interventions for improving sleep in PD patients hold promise as a treatment for mitigating symptoms and improving quality of life in PD.

Deceased donor urinary Dickkopf-3 associates with future allograft function following kidney transplantation

Predicting future kidney allograft function is challenging. Novel biomarkers, such as urinary Dickkopf-3 (uDKK3), may help guide donor selection and improve allograft outcomes. In this prospective multicenter pilot trial, we investigated whether donor uDKK3 reflects organ quality and is associated with future allograft function. We measured uDKK3/crea ratios (uDKK3/crea) from 95 deceased and 46 living kidney donors. Prenephrectomy uDKK3/crea levels were 100× higher in deceased than in living donors (9888 pg/mg vs 113 pg/mg; P < .001). Among deceased donor transplantations, recipients were stratified by their corresponding uDKK3/crea donor levels ranging below (group A, n = 68) or above (group B, n = 65) median. The primary end point of best estimated glomerular filtration rate (eGFR) within the first 3 months after kidney transplantation was superior in group A (56.3 mL/min/1.73 m2) than that in group B (44.2 mL/min/1.73 m2; P = .0139). Second, the composite clinical end point consisting of death, allograft failure or eGFR decline >50% occurred less frequent in group A. By mixed linear regression modeling, donor uDKK3/crea remained an independent predictor of eGFR after transplantation, with a slope of −4.282 mL/min/1.73 m2 per logarithmic increase in donor uDKK3/crea. In summary, uDKK3 may serve as a noninvasive, donor-dependent biomarker for assessing organ quality and future allograft function.

Exploratory functional and quality of life outcomes with daily consumption of the ketone ester bis-octanoyl (R)-1,3-butanediol in healthy older adults: a randomized, parallel arm, double-blind, placebo-controlled study.

Ketone bodies are metabolites produced during fasting or on a ketogenic diet that have pleiotropic effects on the inflammatory and metabolic aging pathways underpinning frailty in in vivo models. Ketone esters (KEs) are compounds that induce hyperketonemia without dietary changes and that may impact physical and cognitive function in young adults. The functional effects of KEs have not been studied in older adults. Our long-term goal is to examine if KEs modulate aging biology mechanisms and clinical outcomes relevant to frailty in older adults. Here, we report the exploratory functional and quality-of-life outcome measures collected during a 12-week safety and tolerability study of KE (NCT05585762). Randomized, placebo-controlled, double-blinded, parallel-group, pilot trial of 12-weeks of daily KE ingestion. The Clinical Research Unit at the Buck Institute for Research on Aging, California. Community-dwelling older adults (≥ 65 years), independent in activities of daily living, with no unstable acute medical conditions (n = 30). Subjects were randomly allocated (1:1) to consume 25 g daily of either KE (bis-octanoyl (R)-1,3-butanediol) or a taste, appearance, and calorie-matched placebo (PLA) containing canola oil. Longitudinal change in physical function, cognitive function and quality of life were assessed as exploratory outcomes in n = 23 completers (n = 11 PLA, n = 12 KE). A composite functional outcome to describe the vigor-frailty continuum was calculated. Heart rate and activity was measured throughout the study using digital wearables. There were no statistically significant longitudinal differences between groups in exploratory functional, activity-based or quality of life outcomes. Daily ingestion of 25 g of KE did not affect exploratory functional or quality-of-life end points in this pilot cohort of healthy older adults. Future work will address these endpoints as primary and secondary outcomes in a larger trial of pre-frail older adults.

Development and validation of the Florey Dementia Risk Score web-based tool to screen for Alzheimer's disease in primary care

It is estimated that ∼60% of people with Alzheimer's disease (AD) are undetected or undiagnosed, with higher rates of underdiagnosis in low-to middle-income areas with limited medical resources. To promote health equity, we have developed a web-based tool that utilizes easy-to-collect clinical data to enhance AD detection rate in primary care settings. This study was leveraged on the data collected from participants of the Australian Imaging, Biomarker & Lifestyle (AIBL) study and the Religious Orders Study and Memory and Aging Project (ROSMAP). The study included three phases: (1) constructing and evaluating a model on retrospective cohort data (1407 AIBL participants), (2) performing simulated trials to assess model accuracy (30 AIBL participants) and missing data tolerability (30 AIBL participants), and (3) external evaluation using a non-Australian dataset (500 ROSMAP participants). The auto-score machine learning algorithm was employed to develop the Florey Dementia Risk Score (FDRS). All the simulated trials and evaluation were performed using a web-based FDRS tool. FDRS achieved an area under the curve (AUC) of approximately 0.82 [95% CI, 0.75-0.88], with a sensitivity of 0.74 [0.60-0.86] and a specificity of 0.73 [0.70-0.79]. The accuracy of the simulated pilot trial for 30 AIBL participants with complete record was 87% (26/30 correct), while it only slightly decreased (80.0-83.3%, depending on imputation methods) for another 30 AIBL participants with one or two missing data. FDRS achieved an AUC of 0.82 [0.77-0.86] of 500 ROSMAP participants. The FDRS tool offers a potential low-cost solution to AD screening in primary care. The present study warrants future trials of FDRS for optimization and to confirm its generalizability across a more diverse population, especially people in low-income countries. National Health and Medical Research Council, Australia (GNT2007912) and Alzheimer's Association, USA (23AARF-1020292).