Individual Trials Research Articles

Pengembangan Media Pembelajaran EMI-PPKN Berbasis Digital Tematik Kelas V Sekolah Dasar

Abstract: The development of thematic digital-based EMI-PPKN learning media for class V elementary schools, has the aim of knowing the development of valid and practical EMI-PPKN products. The type of research used by researchers in developing EMI-PPKN is R&D (Research and Development), development using the ADDIE model consisting of Analysis, Design, Development, Implementation, Evaluation. The subjects of this research were students in classes V.A and V.B at state elementary school 95 Palembang with a total of 35 students. The data collection techniques used in the research are observation, interviews, questionnaires, based on the results of research by validator experts from three fields, namely media, materials and language, where in this development there are 3 validators covering these 3 fields, so that the percentage of validators from the three experts is 90.83 % categorized as "Very Valid". Then the practicality test of the teacher's response obtained a percentage result of 86.66% categorized as "Very practical", then the one to one (Individual) trial obtained a percentage of 93.88% categorized as "Very practical", then the final trial, namely the small group, received a score percentage of 91.88% in the "Very practical" category. Keywords: Learning Media Development, EMI-PPKN, Digital

Year-Long Cannabis Use for Medical Symptoms and Brain Activation During Cognitive Processes

Cannabis is increasingly being used to treat medical symptoms, but the effects on brain function in those using cannabis for these symptoms are not known. To test whether 1 year of cannabis use for medical symptoms after obtaining a medical cannabis card was associated with increased brain activation during working memory, reward, and inhibitory control tasks, areas of cognition affected by cannabis. This cohort study was conducted from July 2017 to July 2020 among participants from the greater Boston area who were recruited as part of a clinical trial of individuals seeking medical cannabis cards for anxiety, depression, pain, or insomnia symptoms. Participants were aged between 18 and 65 years. Exclusion criteria were daily cannabis use and cannabis use disorder at baseline. Data analysis was conducted from August 2021 to April 2024. Outcomes were whole brain functional activation during tasks involving working memory, reward, and inhibitory control at baseline and after 1 year of medical cannabis card ownership. Imaging was collected from participants before and 1 year after obtaining medical cannabis cards, with 57 participants at baseline (38 female [66.7%]; 6 [10.5%] Black and 45 [78.9%] White participants; 1 [1.8%] Hispanic participant; median [IQR] age, 34.0 [24.0-51.0] years) and 54 participants at 1 year (37 female [68.5%]; 4 [7.4%] Black and 48 [88.9%] White participants; 1 [1.9%] Hispanic participant, median [IQR] age, 36.5 [25.0-51.0] years). Imaging was also collected in 32 healthy control participants at baseline (22 female [68.8%]; 2 [6.2%] Black and 27 [84.4%] White participants; 3 [9.4%] Hispanic participants; median [IQR] age, 33.0 [24.8-38.2] years). In all groups and at both time points, functional imaging revealed canonical activations of the probed cognitive processes. No statistically significant difference in brain activation between the 2 time points (baseline and 1 year) in those with medical cannabis cards and no associations between changes in cannabis use frequency and brain activation after 1 year were found. In this cohort study of adults obtaining medical cannabis cards for medical symptoms, no significant association between brain activation in the areas of cognition of working memory, reward, and inhibitory control and 1 year of cannabis use was observed. The results warrant further studies that probe the association of cannabis at higher doses, with greater frequency, in younger age groups, and with larger, more diverse cohorts.

The impact of trial inclusion criteria on outcomes in DLBCL patients treated with R-CHOP in the first line: a Danish nationwide study

Up to 50% of diffuse large B-cell lymphoma (DLBCL) patients are ineligible for participation in clinical trials. Ineligible patients have inferior outcomes, but less is known about the impact of commonly used organ-function-based inclusion criteria on drug efficacy estimates. Data on DLBCL patients treated with CHOP+/-rituximab were retrieved from the Danish Lymphoma Registry. Trial inclusion criteria were extracted from four international DLBCL trials (REMoDL-B, GOYA, POLARIX, and HOVON-84). Differences in overall survival (OS) and 5-year restricted mean survival differences (5 y-RMSDs) between trial eligible and ineligible patients were computed. The effectiveness of adding rituximab to CHOP was quantified by the 5 y-RMSD between CHOP and R-CHOP-treated patients and the impact of individual trial criteria on estimated effectiveness was quantified by Shapley-values. In total, 4,083 R-CHOP-treated and 890 CHOP-treated DLBCL patients were included. Across the trials, 18.6-29.3% of the included R-CHOP-treated patients were deemed ineligible for trial based on organ function and performance status alone. Ineligible patients had significantly worse survival, with adjusted absolute differences in 5-year OS of 9-15%. The impact of individual criteria on the estimated effectiveness of adding rituximab to CHOP was small (Shapley-value range, −2.74-0.31). Using a smaller set of criteria derived from a data-driven approach, the number of eligible patients increased by 16-38% and the 5 y-RMSD increased by 0.7-3.1 months. In conclusion, OS among trial ineligible DLBCL patients is inferior as expected, but relaxing trial criteria would have increased the number of trial participants without making major changes in estimated efficacy for a hypothetical CHOP versus R-CHOP trial. This does not necessarily imply that trial findings based on selected patients are unreliable, as the estimated effectiveness of adding rituximab to CHOP was only slightly affected by omitting selected inclusion criteria.

N-of-1 trials in epilepsy: A systematic review and lessons paving the way forward.

Defined as prospective single-patient crossover studies with repeated paired cycles of active and control intervention, N-of-1 trials have gained attention as an option to obtain high-quality evidence of efficacy, particularly for patients with rare epilepsies in whom conduction of well-powered randomized controlled trials can be challenging. The objective of this systematic review is to provide an appraisal of the literature on N-of-1 trials in individuals with epilepsy. We searched PubMed and Embase on January 12, 2024, for studies meeting the following criteria: prospectively planned, within-patient, multiple-crossover design in individuals with epilepsy and outcomes related to comorbidities. Information on design, outcome measurements, intervention, and analyses was retrieved. Risk of bias assessment was performed using the Risk of Bias in N-of-1 Trials (RoBiNT) scale. We highlighted methodological aspects of the N-of-1 trials identified and discuss future recommendations. Five studies met our inclusion criteria. An additional multiple-crossover trial that evaluated treatment effects exclusively at group level was also included because of its relevance to N-of-1 study methodology. The studies enrolled individuals with focal seizures, absences or cognitive impairement and electrographic discharges. Treatments included established or investigational antiseizure medications, off-label medications, neurostimulation or lifestyle intervention. Three of the five N-of-1 trials reported on individual cases. The studies' strengths were the use of individualized treatment dosages and symptom-specific patient-reported outcomes. Limitations were related to minimal reporting of baseline characteristics and seizure burden. The trials identified by our search exemplify how the N-of-1 design can be applied to assess interventions in individuals with epilepsy-related disorders. Future N-of-1 trials of antiseizure interventions should take into account baseline seizure frequency, should apply statistical models suited to capture seizure frequency changes reliably and make predefined interim assessments. Non-seizure outcome measures evaluable over short periods should be considered. Tailored N-of-1 methodology could pave the way to evidence-based, treatment selection for patients with rare epilepsies.

Saffron (Crocus sativus) and its constituents in ovalbumin-induced asthma model: a preclinical systematic review and meta-analysis.

Animal and human studies have demonstrated that the saffron and the active components of saffron, including crocin, crocetin, and safranal, possess anti-inflammatory, antioxidant, and immunomodulatory properties. In this meta-analysis, the preclinical evidence and potential mechanism of saffron were explored in an animal model of ovalbumin-induced asthma. Studies related to saffron and its constituents in an animal model of ovalbumin-induced asthma from the beginning to March 2024 were searched from Scopus, PubMed, and Web of Science databases. The methodological quality of the studies was evaluated using the 15-item CAMARADES checklist. Data analysis was performed using STATA software version 17. Thirteen studies with 536 animals (268 animals in the intervention group and 268 animals in the ovalbumin-induced group) were analyzed. The meta-analysis findings demonstrated that saffron and its constituents played a significant role in reducing total WBC, eosinophil, lymphocyte, and monocyte counts. Moreover, saffron showed a significant decrease in the levels of IL-4, IL-5, IL-13, IgE, histamine, endothelin, nitric oxide, and nitrite. Moreover, saffron was found to elevate EC50 thresholds and lower maximum response rates in experimental animals. The analysis revealed a significant identification of modulation in endoplasmic reticulum (ER) stress markers and miRNAs pathways. Saffron and its components may impact ovalbumin-induced asthma model in animals through anti-inflammatory, antioxidant, and immunomodulatory pathways, as well as improving pulmonary function and modulating ER stress markers and miRNAs pathways. As a result, saffron should be considered for further clinical trials in individuals suffering from asthma.

The Digital Platform and Its Emerging Role in Decentralized Clinical Trials.

Decentralized clinical trials (DCTs) are becoming increasingly popular. Digital clinical trial platforms are software environments where users complete designated clinical trial tasks, providing investigators and trial participants with efficient tools to support trial activities and streamline trial processes. In particular, digital platforms with a modular architecture lend themselves to DCTs, where individual trial activities can correspond to specific platform modules. While design features can allow users to customize their platform experience, the real strengths of digital platforms for DCTs are enabling centralized data capture and remote monitoring of trial participants and in using digital technologies to streamline workflows and improve trial management. When selecting a platform for use in a DCT, sponsors and investigators must consider the specific trial requirements. All digital platforms are limited in their functionality and technical capabilities. Integrating additional functional modules into a central platform may solve these challenges, but few commercial platforms are open to integrating third-party components. The lack of common data standardization protocols for clinical trials will likely limit the development of one-size-fits-all digital platforms for DCTs. This viewpoint summarizes the current role of digital platforms in supporting decentralized trial activities, including a discussion of the potential benefits and challenges of digital platforms for investigators and participants. We will highlight the role of the digital platform in the development of DCTs and emphasize where existing technology is functionally limiting. Finally, we will discuss the concept of the ideal fully integrated and unified DCT and the obstacles developers must address before it can be realized.

A Transient High-dimensional Geometry Affords Stable Conjunctive Subspaces for Efficient Action Selection.

Flexible action selection requires cognitive control mechanisms capable of mapping the same inputs to different output actions depending on the context. From a neural state-space perspective, this requires a control representation that separates similar input neural states by context. Additionally, for action selection to be robust and time-invariant, information must be stable in time, enabling efficient readout. Here, using EEG decoding methods, we investigate how the geometry and dynamics of control representations constrain flexible action selection in the human brain. Participants performed a context-dependent action selection task. A forced response procedure probed action selection different states in neural trajectories. The result shows that before successful responses, there is a transient expansion of representational dimensionality that separated conjunctive subspaces. Further, the dynamics stabilizes in the same time window, with entry into this stable, high-dimensional state predictive of individual trial performance. These results establish the neural geometry and dynamics the human brain needs for flexible control over behavior.

PENGEMBANGAN MEDIA PEMBELAJARAN BERBASIS ISPRING SUITE PADA MATERI BANGUN RUANG SISI DATAR

This research aims to develop ispring suite-based learning media on flat side space building materials reviewed from the aspects of feasibility, practicality and effectiveness. The research uses the R&D method, namely (Research and Development), and uses the ADDIE learning design model (Analysis, Design, Development, Implementation and Evaluation). The media developed uses ispring suite software, which is software used to create interactive learning media in the form of material presentations, material videos, practice questions, and quizzes. The test subjects in this study used individual and small group trials. The individual trial was 3 students of class VIII Madrasah Tsanawiyah and for the small group trial, namely 13 students of class VIII Madrasah Tsanawiyah. The results of this study, according to the assessment of media experts and material experts, show that ispring suite-based learning media obtained criteria suitable for use with an average score of 4.1. The results of the trials conducted on individual trials and small group trials showed that the ispring suite-based learning media obtained very practical criteria with an average score of 4.3. The ispring suite-based learning media also obtained very effective criteria with an average N-gain score of 0.87 based on the results of individual trial tests and small group trial test results.

PRACTICE: Development of a Core Outcome Set for Trials of Physical Rehabilitation in Critical Illness.

Rationale Findings from individual trials of physical rehabilitation interventions in critically ill adults have limited potential for meta-analysis and informing clinical decision-making due to heterogeneity in selection and reporting of outcomes used for evaluation. Objective The objective of this study was to determine a core outcome set (COS) for use in all future trials evaluating physical rehabilitation interventions delivered across the critical illness continuum of recovery. Methods An international, two-round, online, modified Delphi consensus process, following recommended standards, was conducted. Participants (N=329) comprised three stakeholder groups (Researchers, n=58 (18%); Clinicians, n=247 (75%); Patients and Caregivers, n=24 (7%)), and represented 26 countries and 9 healthcare professions. Participants rated the importance of a range of relevant outcomes. Outcomes included in the COS were those prioritised of "critical importance" by all three stakeholder groups. Results Survey response rates were 88% (Round 1) and 91% (Round 2). From a total of 32 initial outcomes, the following outcomes reached consensus for inclusion in the COS: Physical Function, Activities of Daily Living, Survival, Health-related Quality of Life, Exercise Capacity, Cognitive Function, Emotional and Mental Wellbeing, and Frailty. Conclusion This study developed a consensus-generated COS for future clinical research evaluating physical rehabilitation interventions in critically ill adults across the continuum of recovery. Ascertaining recommended measurement instruments for these core outcomes is now required to facilitate implementation of the COS. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

N-acetylcysteine as a treatment for substance use cravings: A meta-analysis.

N-acetylcysteine (NAC) may serve as a novel pharmacotherapy for substance use and substance craving in individuals with substance use disorders (SUDs), possibly through its potential to regulate glutamate. Though prior meta-analyses generally support NAC's efficacy in reducing symptoms of craving, individual trials have found mixed results. The aims of the this updated meta-analysis were to (1) examine the efficacy of NAC in treating symptoms of craving in individuals with a SUD and (2) explore subgroup differences, risk of bias, and publication bias across trials. Database searches of PubMed, Cochrane Library, and ClinicalTrials.gov were conducted in June and July of 2023 to identify relevant randomized control trials (RCTs). The meta-analysis consisted of 9 trials which analyzed data from a total of 623 participants. The most targeted substance in the clinical trials was alcohol (3/9; 33.3%), followed by tobacco (2/9; 22.2%) and multiple substances (2/9; 22.2%). Meta-analysis, subgroup analyses, and leave-one-out analyses were conducted to examine treatment effect on craving symptoms and adverse events (AEs). Risk of bias assessments, Egger's tests, and funnel plot tests were conducted to examine risk of bias and publication bias. NAC did not significantly outperform placebo in reducing symptoms of craving in the meta-analysis (SMD = 0.189, 95% CI = -0.015 - 0.393). Heterogeneity was very high in the meta-analysis (99.26%), indicating that findings may have been influenced by clinical or methodological differences in the study protocols. Additionally, results indicate that there may be publication bias present. Overall, our findings are contrary to those of prior meta-analyses, suggesting limited impact of NAC on substance craving. However, the high heterogeneity and presence of publication bias identified warrants cautious interpretation of the meta-analytic outcomes.

Dense and persistent odor representations in the olfactory bulb of awake mice.

Recording and analysis of neural activity is often biased toward detecting sparse subsets of highly active neurons, masking important signals carried in low magnitude and variable responses. To investigate the contribution of seemingly noisy activity to odor encoding, we used mesoscale calcium imaging from mice of both sexes to record odor responses from the dorsal surface of bilateral olfactory bulbs (OBs). The outer layer of the mouse OB is comprised of dendrites organized into discrete "glomeruli", which are defined by odor receptor-specific sensory neuron input. We extracted activity from a large population of glomeruli and used logistic regression to classify odors from individual trials with high accuracy. We then used add-in and drop-out analyses to determine subsets of glomeruli necessary and sufficient for odor classification. Classifiers successfully predicted odor identity even after excluding sparse, highly active glomeruli, indicating that odor information is redundantly represented across a large population of glomeruli. Additionally, we found that Random Forest feature selection informed by Gini Inequality (RFGI) reliably ranked glomeruli by their contribution to overall odor classification. RFGI provided a measure of "feature importance" for each glomerulus that correlated with intuitive features like response magnitude. Finally, in agreement with previous work, we found that odor information persists in glomerular activity after odor offset. Together, our findings support a model of olfactory bulb odor coding where sparse activity is sufficient for odor identification, but information is widely, redundantly available across a large population of glomeruli, with each glomerulus representing information about more than one odor.Significance statement This study leverages meso-scale imaging and machine learning to investigate how odor information is first represented in the brain. Typically, recordings of neuronal activity focus on active individual cells, potentially overlooking broader variations in neuronal responses across populations. Our results demonstrate that a considerable amount of olfactory information is redundantly distributed across a large proportion of olfactory bulb glomeruli. Even after excluding a majority of glomeruli, odor identification remained possible. These findings indicate that, although a few glomeruli are sufficient for odor recognition, an abundance of additional information is represented across a broad population. Understanding how the brain manages redundant olfactory information will shed light on its adaptive mechanisms for navigating diverse real-world circumstances and responding to fluctuating internal states.

Long-term prognostic value of contemporary stress echocardiography in patients with suspected or known coronary artery disease: systematic review and meta-analysis

BackgroundLong-term outcome of contemporary stress echocardiography has not been systematically assessed.ObjectiveTo evaluate the association between results of stress echocardiography and patients’ outcomes with suspected coronary artery disease using randomised controlled...

Brain Evoked Response Qualification Using Multi-Set Consensus Clustering: Toward Single-Trial EEG Analysis.

In event-related potential (ERP) analysis, it is commonly assumed that individual trials from a subject share similar properties and originate from comparable neural sources, allowing reliable interpretation of group-averages. Nevertheless, traditional group-level ERP analysis methods, including cluster analysis, often overlook critical information about individual subjects' neural processes due to using fixed measurement intervals derived from averaging. We developed a multi-set consensus clustering pipeline to examine cognitive processes at the individual subject level. Initially, consensus clustering from diverse methods was applied to single-trial EEG epochs of individual subjects. Subsequently, a second level of consensus clustering was performed across the trials of each subject. A newly modified time window determination method was then employed to identify individual subjects' ERP(s) of interest. We validated our method with simulated data for ERP components N2 and P3, and real data from a visual oddball task to confirm the P3 component. Our findings revealed that estimated time windows for individual subjects provide precise ERP identification compared to fixed time windows across all subjects. Additionally, Monte Carlo simulations with synthetic single-trial data demonstrated stable scores for the N2 and P3 components, confirming the reliability of our method. The proposed method enhances the examination of brain-evoked responses at the individual subject level by considering single-trial EEG data, thereby extracting mutual information relevant to the neural process. This approach offers a significant improvement over conventional ERP analysis, which relies on the averaging mechanism and fixed measurement interval.

DOSage of Exercise for chronic low back pain disorders (DOSE): protocol for a systematic review with dose-response network meta-analysis

Chronic low back disorders are the leading cause of direct and indirect healthcare burden globally. Exercise training improves pain intensity, mental health and physical function. However, the optimal prescription variables...

Time Gained to Cardiovascular Disease by Intensive Lipid-Lowering Therapy: Results of Individual Placebo-Controlled Trials and Pooled Effects.

Despite the effect on blood lipid levels, the clinical benefits of intensive versus standard pharmacological lipid-lowering therapy remain unclear. Previous reviews have presented relative effects on the risk of clinical outcomes, but not the absolute risk reductions (ARRs) and the time gained to a clinical outcome, also called outcome postponement (OP). The aim of this study was to estimate the effect of intensive versus standard lipid-lowering therapy in terms of ARR and OP of major adverse cardiovascular events (MACE), myocardial infarction (MI), stroke, and all-cause mortality. We searched PubMed, Embase, and prior reviews to identify trials comparing intensive versus standard lipid-lowering therapy for the risk of cardiovascular disease. We extracted the number of patients with MACE, MI, stroke, and all-cause mortality. Risk of bias was assessed according to the five domains of the Cochrane Risk of Bias Tool 2.0. We calculated ARRs and OPs to assess the clinical benefits of intensive versus standard therapy for each outcome. We conducted meta-analyses standardizing the results to 2 and 5 years of follow-up. We identified 11 double-blind, randomized, controlled trials (n=101,357). The follow-up period ranged from 1.5 to 7.0 years, with an average follow-up duration of 3.7years. Risk of bias was generally high. During an estimated 2years of intensive versus standard lipid-lowering therapy, 1.1% (95% confidence interval [CI] 0.7-1.5) fewer patients had MACE and the OP of MACE was 4.1 days (95% CI 2.6-5.6). The effects were 0.7% (95% CI 0.4-0.8) and 2.5 days (95% CI 1.6-3.3) for MI, 0.2% (95% CI 0.1-0.3) and 0.9 days (95% CI 0.5-1.2) for stroke, and 0.2% (95% CI -0.1 to 0.4) and 0.6 days (95% CI -0.4 to 1.5) for all-cause death. During on average 5 years of intensive versus standard lipid-lowering therapy, 2.4% (95% CI 1.5-3.3) fewer patients had MACE and the time gained to MACE was 23.5 days (95% CI 14.9-32.0). The effects were 1.5% (95% CI 1.0-2.1) and 14.6 days (95% CI 9.3-20.0) for MI, 0.6% (95% CI 0.4-0.8) and 5.3 days (95% CI 3.3-7.4) for stroke, and 0.4% (95% CI -0.2 to 0.1) and 3.6 days (95% CI -2.1 to 9.2) for all-cause death. Intensive lipid-lowering therapy during 2 or 5years did not lead to fewer deaths or lifetime gained, and the effects on MI and stroke were negligible. The largest effect was that MACE did not occur in two of 100 patients and was postponed 3-4weeks after 5years of intensive treatment. Given the small effect, patients should receive this information as part of shared decision making.

Exploring the Impact of a Sleep App on Sleep Quality in a General Population Sample: Pilot Randomized Controlled Trial.

A third of adults in Western countries have impaired sleep quality. A possible solution involves distributing sleep aids through smartphone apps, but most empirical studies are limited to small pilot trials in distinct populations (eg, soldiers) or individuals with clinical sleep disorders; therefore, general population data are required. Furthermore, recent research shows that sleep app users desire a personalized approach, offering an individually tailored choice of techniques. One such aid is Peak Sleep, a smartphone app based on scientifically validated principles for improving sleep quality, such as mindfulness meditation and cognitive behavioral therapy. We aimed to test the impact of the smartphone app Peak Sleep on sleep quality and collect user experience data to allow for future app development. This was a 2-arm pilot randomized controlled trial. Participants were general population adults in the United Kingdom (aged ≥18 years) who were interested in improving their sleep quality and were not undergoing clinical treatment for sleep disorder or using sleep medication ≥1 per week. Participants were individually randomized to receive the intervention (3 months of app use) versus a no-treatment control. The intervention involved free access to Peak Sleep, an app that offered a choice of behavioral techniques to support better sleep (mindfulness, cognitive behavioral therapy, and acceptance commitment therapy). The primary outcome was sleep quality assessed using the Insomnia Severity Index at baseline and 1-, 2-, and 3-month follow-ups. Assessments were remote using web-based questionnaires. Objective sleep data collection using the Oura Ring (Ōura Health Oy) was planned; however, because the COVID-19 pandemic lockdowns began just after recruitment started, this plan could not be realized. Participant engagement with the app was assessed using the Digital Behavior Change Intervention Engagement Scale and qualitative telephone interviews with a subsample. A total of 101 participants were enrolled in the trial, and 21 (21%) were qualitatively interviewed. Sleep quality improved in both groups over time, with Insomnia Severity Index scores of the intervention group improving by a mean of 2.5 and the control group by a mean of 1.6 (between-group mean difference 0.9, 95% CI -2.0 to 3.8), with was no significant effect of group (P=.91). App users' engagement was mixed, with qualitative interviews supporting the view of a polarized sample who either strongly liked or disliked the app. In this trial, self-reported sleep improved over time in both intervention and control arms, with no impact by group, suggesting no effect of the sleep app. Qualitative data suggested polarized views on liking or not liking the app, features that people engaged with, and areas for improvement. Future work could involve developing the app features and then testing the app using objective measures of sleep in a larger sample. ClinicalTrials.gov NCT04487483; https://www.clinicaltrials.gov/study/NCT04487483.

Protocol for a randomized controlled trial of moderate intensity interval training in individuals with chronic obstructive pulmonary disease and obstructive sleep apnea overlap syndrome who have excessive daytime sleepiness

BackgroundThe term “Overlap Syndrome” (OS) describes the presence of both chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) in a single individual. Excessive daytime sleepiness (EDS) is a common symptom of OS shown to be associated with an increased risk of cardiovascular disease (CVD) that could be reduced through exercise. Thus, we propose to investigate a novel exercise intervention in individuals with the EDS-OS phenotype as they are at highest risk of CVD yet have the greatest barriers to exercise. MethodsWe will conduct a single-site, randomized, two-arm, parallel group-controlled exercise trial in individuals with EDS-OS. The Epworth Sleepiness Scale (ESS) will be assessed at baseline. Individuals with OS and the EDS-OS phenotype (ESS >10) (n = 46) will be randomized to a moderate intensity interval training (MIIT, i.e. intervals of 5 min at 50% VO2peak followed by 3 min of active recovery at 10% VO2peak) or a control group of standard of care. We will investigate if MIIT intervention decreases the risk of CVD in EDS-OS, which will be assessed by: 1) quality of life, measured by the 36-Item Short Form Health Survey; 2) physical activity, measured by daily step counts; and 3) cardiovascular health, assessed as VO2peak, flow-mediated dilation and serum high sensitivity C-reactive protein, lipids, and glucose. ConclusionOur findings will guide future development and implementation of exercise interventions that could reduce the risk of CVD in the understudied EDS-OS phenotype.

Broad versus narrow research questions in evidence synthesis: A parallel to (and plea for) estimands.

There has been a transition from broad to more specific research questions in the practice of network meta-analysis (NMA). Such convergence is also taking place in the context of individual registrational trials, following the recent introduction of the estimand framework, which is impacting the design, data collection strategy, analysis and interpretation of clinical trials. The language of estimands has much to offer to NMA, particularly given the "narrow" perspective of treatments and target populations taken in health technology assessment.

Evaluating practice effects across learning trials – ceiling effects or something more?

ABSTRACT Background Practice effects (PE) are traditionally considered improvements in performance observed resulting from repeated exposure to test materials across multiple testing sessions. While PE are commonly observed for memory tests, this effect has only been considered in summary total scores. The current objective was to consider PE in summary total scores, individual learning trials, and learning slopes. Method One-week PE for individual trial and learning slope performance was examined on the BVMT-R and HVLT-R in 151 cognitively intact participants and 131 participants with Mild Cognitive Impairment (MCI) aged 65 years and older. Results One-week PE were observed across all trials and summary total scores for both memory measures and diagnostic classifications, despite the potential for ceiling effects to limit improvement on retesting. PE were largest on the first trial relative to subsequent learning trials. This effect was diminished – but not eliminated – in participants with MCI. Conversely, no PE were observed for learning slope scores, which was counter to expectations and likely confounded by ceiling effects. Conclusions PE were present across learning trials but not learning slopes, and the initial learning trial at follow-up tended to benefit most from PE relative to subsequent learning trials. Ceiling effects appeared to influence PE for learning slopes more than learning trials. These results highlight the potential diagnostic utility of PE across individual learning trials and inform how they are distributed at follow-up, while also suggesting that learning slopes may be generally stable during longitudinal assessment.

Tri Hita Karana Based Yoga Model Instrument for Independent Student Exchange Students

Implementing the Tri Hita Karana concept in character and spiritual values education in higher education significantly impacts students' holistic well-being. However, developing assessment instruments for implementing this concept is still lacking. This research aims to develop a Tri Hita Karana-based yoga model instrument for Merdeka exchange students. This type of research is development research using the ADDIE method. The subjects of this research were 2 learning content experts, 2 language experts, and 2 learning design experts. The trial subjects were 30 independent exchange students (3 in individual trials and 27 in small group trials). Data collection methods used include observation, interviews, and questionnaires. The instrument used in this research was a questionnaire sheet. The techniques used to analyze data are qualitative descriptive analysis and quantitative and inferential statistics. The research results, namely the assessments given by learning content experts, obtained an average score of 94.5%, resulting in very good qualifications. The assessment results given by language experts were 93% (very good qualifications). The assessment results given by learning design experts were 96.5% (very good qualifications). The results of the practicality test given by the lecturer received an average score of 96% (very practical). The results of the individual trial assessment were 92% and small group trials 95%, so getting a very practical qualification. The t-test results show a difference in the average value of holistic well-being among students after using the Tri Hita Karana Based Yoga Model Instrument. It was concluded that the Tri Hita Karana Based Yoga Model Instrument is feasible and effective to use to improve the holistic well-being of independent exchange students.