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The apps for drawing are present in our children's life. Nevertheless, little is known about the impact of mobile technology on the freehand drawing educational activity. There are few works which are contextualised within short periods of time, with teachers who are not theirs and, in some cases, outside the children's classroom. In this paper, we are focussed on the use of technology on freehand drawing activity. Thus, we have compared the graphics produced by 4- and 5-year-old children with paper&crayon in comparison with those with tablet-finger. Children made the drawings during a planned free-drawing activity, in their ordinary classrooms, with their teachers and during five sessions. Assessment of drawings has evidenced tablet feasibility for making graphics. Nevertheless, with the passing of time, quality of graphics (tablet-finger vs paper&crayons), are nearly matched, demonstrating the low impact level technology has on this activity. In addition, if drawings are analysed specifically according to ages, results have shown that both groups have to develop adaptation strategies of visual perceptual skills and fine motor skills for the touch screen in order to obtain the same quality in the drawings made on both support types. [ABSTRACT FROM AUTHOR]

This document discusses the key concepts of translational research in the field of ophthalmology. Translational research aims to bridge the gap between existing knowledge and medical practice, with the goal of benefiting patients. It involves the transfer of diagnostic and therapeutic advances from the laboratory to clinical practice. The document explores the stakeholders of translational research, the scope of translational medicine, the components of translational research, barriers to its success, and future directions. It emphasizes the importance of collaboration and communication among different stakeholders to promote effective translational research. [Extracted from the article]

The application of STEM (Science, Technology, Engineering, and Math) education in solving real-world problems is challenging. To tackle this challenge, a project-based learning approach that integrates robots with cost-effective self-made toys to problem-solving was adopted to assist rural primary school students to apply STEM skills. The purpose of this study was to evaluate the effects of the project-based learning approach which includes lecturing and hands-on activities on primary school students' STEM learning outcomes and attitudes. An experiment was conducted with 25 primary school students who voluntarily participated in a STEM summer-camp programme. Students were asked to assemble a paper house equipped with an IoT control module and LED light switches, and write and edit robot scripts to produce a robot-based storytelling narrative using the paper house they made as a context. The results show that the project-based learning approach was an effective approach for cultivating primary school students' STEM knowledge and skills as evidenced from the post-written test. The relationships between the students' STEM learning outcomes and attitudes were also confirmed by a clustering analysis. Students who had higher learning attitudes also achieved higher STEM learning outcomes; the findings are also supported by the feedback from the open-ended questionnaire items. This study suggests that integrating low-cost self-made toys and robots in project-based learning activities is an effective and practical approach to enhance primary school students' learning outcomes and learning attitudes in STEM education. [ABSTRACT FROM AUTHOR]

Complex and enduring mental health problems require greater treatment resources, usually in the form of multidisciplinary support, including providing psychological therapies. This paper reports on an NHS, tertiary-level specialist psychotherapy service offering Psychodynamic therapies with longer-term, exploratory transdiagnostic approaches to support complexity and sustained personality functioning. This paper adopts a naturalistic study design evaluating the effectiveness of Psychodynamic therapy using pre- and post-outcomes across a 10-year period. A total of n = 474 participants self-report pre- and post-outcome measures were used as the marker of effectiveness along with therapist assessments during intake and engagement. The findings showed that Psychodynamic therapy was effective in reducing psychological distress based on service-user self-report and therapist assessments. While intake scores varied by socio-demographic factors, the rate of change across most groups was similar. There were several limitations relating to data quality and completeness which reflect the naturalistic design. Despite the limits of a naturalistic design, this study provides evidence of support for the place of Psychodynamic therapies within NHS mental health care, catering to those with complex and enduring mental health problems. [ABSTRACT FROM AUTHOR]

The validity of driving simulators is a topic that has been addressed ever since their first use. In practice, a comparison of field data and simulator data is often used for validation purposes. A systematic literature search was conducted which identified large heterogeneity in both study designs and statistical methods used in research on simulator validity. Most of the included studies concluded simulator validity (thus equivalence of field data and simulator data) from non-significant results in Null-Hypothesis Significance Testing (NHST), which is a well-known yet somewhat controversial practice. In this work, the consequences of both study design choice and the choice of the statistical method are outlined and alternatives such as using Bayes factor hypothesis testing and equivalence tests are discussed and applied to a real data example. The present paper is intended to shed light on the influence of the statistical method on conclusions drawn from experimental data. For research on driving simulator validity, we highly encourage the use of equivalence tests or Bayes factor hypothesis tests, in particular when evidence of the data suggests that an effect might be absent. [ABSTRACT FROM AUTHOR]

Introduction: Currently, there is no consensus regarding the management of intermittent exotropia (IXT), which includes both surgical and non-surgical treatment options. Nonsurgical management of IXT has been suggested and includes watchful observation, patching, overminus lenses, prism, and vision therapy/orthoptics. While a significant portion of IXT patients are treated by surgery, it is reported that there is a substantial tendency for reoperation or recurrence of IXT. This paper provides a comprehensive review of non-surgical and surgical treatment options for the IXT. Methods: Search strategies involving combination of keywords including intermittent exotropia, divergence excess, basic exotropia, refractive error, glasses, spectacles, natural history, untreated, observe, occlusion, patch, overminus, overcorrecting minus, prism, vision therapy, orthoptic, anti-suppression, fusion exercise, and surgery were used in Medline. All English articles from 01/01/1900 to 01/09/2020 were reviewed. The reference list of the identified articles was also checked for additional relevant articles. Studies focused on animal models or strabismus associated with neurologic disorders or injury were excluded. The following filters were used for surgical management due to the abundance of reports: full text, randomized controlled trial, review, in the last 5 years. Results: Appropriate optical correction of refractive error is generally the starting point for all management approaches, but there is a lack of randomized clinical trial data regarding this treatment modality. Randomized clinical trial data indicate that both observation and occlusion are reasonable management options for children 3–10 years old, and there were insufficient data to recommend occlusion for children 12–35 months old. While overminus lenses were found to improve the control of IXT when assessed wearing overminus spectacles, this improvement did not persist after the treatment ended. The result of the only randomized clinical trial on the effectiveness of base-in prism indicated that this treatment is no more effective than nonprism spectacles for improving control. A recent randomized clinical trial showed that vision therapy/orthoptics is effective in improving the control of IXT when compared to observation alone. Surgery was found to alter a number of clinical characteristics of IXT, including reducing the distance and near angle of deviation, reducing photophobia, improving health-related quality of life, stereopsis, and the Newcastle Control Score. However, there are no randomized clinical trial data comparing surgery with a control group such as placebo or a no treatment observation group. Discussion: Rigorously designed clinical trials to investigate the effectiveness of non-surgical and surgical treatments for intermittent exotropia are needed. [ABSTRACT FROM AUTHOR]

Dysregulated JAK/STAT hyperactivity is essential to the pathogenesis of myelofibrosis, and JAK inhibitors are the first-line treatment option for many patients. There are four FDA-approved JAK inhibitors for patients with myelofibrosis. Single-agent JAK inhibition can improve splenomegaly, symptom burden, cytopenias, and possibly survival in patients with myelofibrosis. Despite their efficacy, JAK inhibitors produce variable or short-lived responses, in part due to the large network of cooperating signaling pathways and downstream targets of JAK/STAT, which mediates upfront or acquired resistance to JAK inhibitors. Synergistic inhibition of JAK/STAT accessory pathways can increase the rates and duration of response for patients with myelofibrosis. Two recently reported, placebo-controlled phase III trials of novel agents added to JAK inhibition met their primary endpoint, and additional late-stage studies are ongoing. This paper will review role of dysregulated JAK/STAT signaling, biological plausible additional therapeutic targets and the recent advancements in combination strategies with JAK inhibitors for myelofibrosis. [ABSTRACT FROM AUTHOR]

Background:Objective:Methods:Results:Conclusion:Trial registration:Fatigue is a common problem following the acute phase of COVID-19. Potential interventions to reduce fatigue and improve quality of life are appropriate.The study aimed to investigate the effect of auriculotherapy on persistent fatigue in recovered patients from acute phase COVID-19.This double-blind clinical trial was conducted in 2022 in Kashan, Iran on 52 recovered patients reporting persistent fatigue following acute phase COVID-19. A convenience sample was selected and randomly assigned to sham and intervention groups. The intervention group received four weeks of auriculotherapy with Vaccaria seeds attached to six fatigue-related auriculotherapy points on both ears. In the sham group, adhesive tapes were attached to the same points. Fatigue was assessed by the Chalder Fatigue Scale before (T0), after (T1), and four weeks after (T2) the intervention. Both per-protocol and intention-to-treat analyses were used.The two groups differed on financial status and hospitalization history (p < 0.05). The time-group interaction effect was significant for fatigue after adjusting for confounders (p < 0.0001). Fatigue scores of the intervention group were significantly lower than the sham group at T1 and T2 (p < 0.0001). In addition, fatigue scores in the intervention group decreased significantly over time, while in the sham group, fatigue first decreased briefly and then increased (p < 0.05).This initial trial suggested that auriculotherapy may reduce intensity of fatigue and therefore could potentially be integrated into rehabilitation programs for patients with prolonged COVID-19.Iranian Registry of Clinical Trials identifier: IRCT20100211003329N9. [ABSTRACT FROM AUTHOR]

In vocational education and training of computer literacy as part of vocational rehabilitation, learners often work on problem-solving exercises as self-study assignments, and check if their answers are correct. Sighted learners can get information on their incorrect answers by comparing their answers with the correct answers. However, learners with visual impairments largely depend on their teachers for getting this feedback. To remove this dependence, we designed a self-checking system for learners with visual impairments to verify the correctness of their answers. In this paper, we report the results of a usability study to evaluate whether learners with visual impairments can self-check spreadsheet problem-solving exercises using our system in a teacherless environment. Usability evaluation experiment was conducted using 2 × 2 crossover design with people with visual impairments (n = 11). The participants checked their answers (detected and corrected errors) after working on problem-solving exercises in two ways: (i) manually; and (ii) using our system. The system usability was evaluated by measuring Detection-And-Correction (DAC) ratio as effectiveness, time taken and the number of steps required for DAC as efficiency, and System Usability Scale score as satisfaction. The results show that all the participants could complete the DAC task by using our system, and the time required for DAC task was significantly reduced by using our system as compared to by checking manually. Our system enables learners with visual impairments to self-check problem-solving exercises answers. However, to increase the user satisfaction, the number of required keystrokes needs to be decreased. Vocational rehabilitation for learners with visual impairments to improve their computer literacy is becoming increasingly important. Learners with visual impairments have the potential to acquire computer literacy in a teacherless environment by using simple assistive software like our self-checking system. Simple assistive software for learners with visual impairments like our self-checking system may have a positive effect not only on learners with visual impairments but also on sighted people. Moreover, our system reduces the teaching load of the teachers so that they can be more effective in helping learners with visual impairments. [ABSTRACT FROM AUTHOR]

AbstractClinical trials are an essential component of the drug development process, providing crucial data on the efficacy and safety of new treatments. However, traditional clinical trial designs can be inefficient and ineffective, leading to increased costs and a higher risk of failure. The FDA Oncology Center of Excellence (OCE) has recently initiated Project Optimus to reform the dose selection paradigm for oncology treatments. We propose the adaptive seamless phase II/III clinical trial designs (ASD) with the sequential estimation-adjusted urn (SEU) model for randomization to achieve efficient and ethical objectives. However, the combination of ASD and SEU poses a challenge in controlling the type I error rate: ASD exerts a dual influence of multiplicity and selection; all the responses and treatment assignments are not independent due to SEU. In this paper, we investigated how to overcome these difficulties, utilize the two adaptive approaches’ advantages, and control the type I error rate. We provide a theoretical foundation for this procedure, and numerical studies demonstrate that our methods can assign more people to better treatments, leading to fewer failures while still controlling the type I error rate and preserving power. [ABSTRACT FROM AUTHOR]

In the era of personalized medicine, there is an increasing interest in the identification of patients who may benefit from or be sensitive to a specific type of treatment. Recently a threshold linear mixed model was proposed to identify treatment-sensitive subgroups based on a continuous covariate when longitudinal measurements are the outcomes of the study. This model assumes, however, a normal distribution for these measurements. In some studies, the longitudinal measurements are restricted in an interval and subject to floor and ceiling effects caused by a portion of subjects with measurements on the boundaries of the interval, which would violate the normality assumption. In this paper, a threshold mixed-effects Tobit model is introduced to overcome this problem. The proposed models and inference procedures are assessed through simulation studies, as well as an application to the analysis of data from a randomized clinical trial. [ABSTRACT FROM AUTHOR]

Recently, interest has grown in the development of dose-finding methods that consider both toxicity and efficacy as endpoints. Along with responses on these, the incorporation of pharmacokinetic (PK) data can be beneficial in terms of patients’ safety and can also increase the efficiency of the design for finding the best dose for the next phase. In this paper, the maximum concentration (${C_{\max }}$Cmax) is used as the PK measure guiding the dose selection. The ethically attractive approach, which is based on the probability of efficacy, is used as a dose optimisation criterion. At each stage of an adaptive trial, that dose is selected for which the criterion is maximised, subject to the constraints imposed on the ${C_{\max }}$Cmax and the probability of toxicity. The inter-patient variability of the PK model parameters is considered, and population $D$D-optimal sampling time points for measuring the concentration of a drug in the blood are calculated. The method is illustrated with a one-compartment PK model with first-order absorption, with the parameters being assumed to be random. The Cox model for bivariate binary responses is employed to model the dose–response outcomes. The results of a simulation study for several plausible dose–response scenarios show a significant gain in the efficiency of the design, as well as a reduction in the proportion of toxic responses. [ABSTRACT FROM AUTHOR]

AbstractIn epidemiological cohort studies, the relative risk is a key measure to gauge the connection between two treatments or exposures. It quantifies the proportional change in the risk of disease due to the application of a specific treatment. However, the conventional methods for calculating relative risk, available in widely-used software, might yield inaccurate results when applied to correlated binary data from studies conducted over time or in clusters. Recently, various techniques have been proposed to estimate the risk ratio for correlated binary data. However, some methods exhibit a tradeoff between maintaining accurate coverage probability (CP) and ensuring an appropriate interval width or location. This paper introduces a new approach to confidently estimating the risk ratio using a hybrid method. This hybrid method combines two distinct confidence intervals (CIs) derived from single risk rates to establish a unified confidence interval for their ratio. Furthermore, we present a methodology to construct a confidence interval for the risk ratio, which builds upon established methods for correlated binary data. This extension incorporates principles such as the design effect and adequate sample sizes commonly used in representative sample surveys. An extensive simulation study is conducted to evaluate the effectiveness of these proposed methods. The performance of the methods is thoroughly examined in various scenarios. Additionally, the practicality of the proposed methods is showcased through three real-life examples. These examples involve comparing the side effects of low-dose tricyclic antidepressants with a placebo, assessing the efficacy of a treatment group in a teratological experiment, and evaluating the efficiency of active drugs in curing infections during clinical trials. [ABSTRACT FROM AUTHOR]

Methods for designing and analyzing multiple arms survival trials that incorporate patient's treatment choice are needed. In these trials, patients are randomized into two groups, random and choice. Participants in the choice group choose their treatment, which is not a current standard practice in randomized clinical trials. In this paper, we propose a new method based on the likelihood function to design and analyze these trials with time to event outcomes in the presence of non-informative right censoring. We use simulations to evaluate the methods for Weibull outcomes, complete and censored. Finally, we provide an illustration for designing a study in which we discuss some design considerations and demonstrate the methods. [ABSTRACT FROM AUTHOR]

In phase 2 clinical trials, we expect to make a right Go or No-Go decision during the interim analysis (IA) and make this decision at the right time. The optimal time for IA is usually determined based on a utility function. In most previous research, utility functions aim to minimize the expected sample size or total cost in confirmatory trials. However, the selected time can vary depending on different alternative hypotheses. This paper proposes a new utility function for Bayesian phase 2 exploratory clinical trials. It evaluates the predictability and robustness of the Go and No-Go decision made during the IA. We can make a robust time selection for the IA based on the function regardless of the treatment effect assumptions. [ABSTRACT FROM AUTHOR]

Selecting a safe and clinically beneficial dose can be difficult in drug development. Dose justification often relies on dose-response modeling where parametric assumptions are made in advance which may not adequately fit the data. This is especially problematic in longitudinal dose-response models, where additional parametric assumptions must be made. This paper proposes a class of longitudinal dose-response models to be used in the Bayesian model averaging paradigm which improve trial operating characteristics while maintaining flexibility a priori. A new longitudinal model for non-monotonic longitudinal profiles is proposed. The benefits and trade-offs of the proposed approach are demonstrated through a case study and simulation. [ABSTRACT FROM AUTHOR]

In recent years, gut microbiome has evolved as a focal point of interest with growing recognition that a well-balanced gut microbiota is highly relevant to an individual's health status. The present review provides a mechanistic insight on the effects of cocoa chemicals on the gut microbiome and further reveals in silico biomarkers, taxonomic and functional features that distinguish gut microbiome of cocoa consumers and controls by using 16S rRNA gene sequencing data. The polyphenols in cocoa can change the gut microbiota either by inhibiting the growth of pathogenic bacteria in the gut such as Clostridium perfringens or by increasing the growth of beneficial microbiota in the gut such as Lactobacillus and Bifidobacterium. This paper demonstrates the holistic effect of gut microbiota on cocoa chemicals and how it impacts human health. We present herein the first comprehensive review and analysis of how raw and roasted cocoa and its products can specifically influence gut homeostasis, and likewise, how microbiota metabolizes cocoa chemicals. In addition to that, our 16S rRNA amplicon sequencing analysis revealed that the flavone and flavonols metabolism, aminobenzoate degradation and fatty acid elongation pathways represent the three most important signatures of microbial functions associated with cocoa consumption. [ABSTRACT FROM AUTHOR]

Haloperidol, the first butyrophenone neuroleptic, was created in Europe by Janssen Pharmaceuticals in 1958 and was introduced swiftly throughout the continent with great enthusiasm. On September 15, 1959, at Janssen's headquarters in Belgium, teams from around Europe praised the effectiveness of haloperidol. In the United States, on the contrary, its introduction was a tremendous failure, plagued by accusations of inefficacy and patent disputes. A clinical trial in Manhattan has been blamed for this commercial failure. The results of the Manhattan trial were seen as radically different from the results obtained in continental Europe. This divide would have considerable impact not only with regard to haloperidol's path on both sides of the Atlantic, but also possibly on the practical experience and theoretical construction of psychiatry. This article tries to reconstruct the story of that trial based mainly on published papers and interviews. Exploring how societal changes and issues of gender and race shaped this process, this investigation attempts to understand and contextualize different possible reasons for this Atlantic rift. [ABSTRACT FROM AUTHOR]

This joint position paper of the American Academy of Clinical Neuropsychology and the National Academy of Neuropsychology sets forth our position on appropriate standards and conventions for computerized neuropsychological assessment devices (CNADs). In this paper, we first define CNADs and distinguish them from examiner-administered neuropsychological instruments. We then set forth position statements on eight key issues relevant to the development and use of CNADs in the healthcare setting. These statements address (a) device marketing and performance claims made by developers of CNADs; (b) issues involved in appropriate end-users for administration and interpretation of CNADs; (c) technical (hardware/software/firmware) issues; (d) privacy, data security, identity verification, and testing environment; (e) psychometric development issues, especially reliability and validity; (f) cultural, experiential, and disability factors affecting examinee interaction with CNADs; (g) use of computerized testing and reporting services; and (h) the need for checks on response validity and effort in the CNAD environment. This paper is intended to provide guidance for test developers and users of CNADs that will promote accurate and appropriate use of computerized tests in a way that maximizes clinical utility and minimizes risks of misuse. The positions taken in this paper are put forth with an eye toward balancing the need to make validated CNADs accessible to otherwise underserved patients with the need to ensure that such tests are developed and utilized competently, appropriately, and with due concern for patient welfare and quality of care. [ABSTRACT FROM AUTHOR]

The author reports on the discussion of the white paper on adaptive dose-ranging designs by the Phrma working Group in Great Britain. He states that the discussion is focusing on methodological issues and drug development. He stresses out that the white paper conducts simulations to compare a traditional approach with alternative design-focused and analysis-focused approaches. He also discusses the different level of phases on the pre-clinical trials.

Acupuncture is being used in more than three hundred treatment facilities for treating substance abuse including cocaine addiction. Previous review papers could not evaluate the role of acupuncture for treating cocaine addiction because of lack of clinical trials at the time. Since then, several important studies were conducted in the field. This paper reviews existing clinical trials using acupuncture to treat cocaine addiction. The existing evidence fails to document the benefit of acupuncture in treating cocaine addiction as the sole treatment. Further efforts to document the efficacy of the NADA protocol to treat cocaine addiction as the sole treatment should be re-evaluated. There is a limited amount of evidence showing possible benefits of acupuncture when used as an adjunctive therapy to complement existing substance abuse treatment program. Future efforts should concentrate on systematic studies investigating the role of acupuncture as an adjunctive treatment for cocaine addiction. In addition, more formative research exploring the efficacy of different types and protocols of acupuncture treatments for cocaine addiction should be thoroughly investigated. [ABSTRACT FROM AUTHOR]

The article discusses the White Paper of adaptive dose-ranging study to address the early phase drug development issues through simulation methods. The author provides the evaluation metrics including the detection of dose-response (DR), identification of clinical outputs, selection of target dose and estimation of DR profile within the observed dose range.

Objective: To evaluate the effect of magnesium sulfate for prevention of eclampsia on blood loss at time of cesarean delivery (CD). Methods: We conducted an electronic based search using the following databases: MEDLINE, PUBMED and the Cochrane Library. The search terms were “magnesium sulfate”, “preeclampsia” and “randomized”. Inclusion criteria were randomized controlled trials of women with preeclampsia who delivered with or without magnesium sulfate therapy for seizure prophylaxis. Only trials with placebo or no treatment comparison groups were included. Primary outcome was postpartum hemorrhage. Secondary outcomes were estimated blood loss, change in hemoglobin, blood transfusion and eclampsia. Results: Five trials met inclusion criteria. The incidence of postpartum hemorrhage was similar between the two groups [magnesium sulfate: 754/4482 (17%); no magnesium sulfate: 775/4427 (18%); RR 0.97, 95% CI 0.88–1.06]. There was no statistical difference between any of the other blood loss outcomes reported in the included studies. The rate of eclampsia with magnesium sulfate was significantly lower than with placebo (42/5604, 0.7%, versus 107/5600, 1.9%; RR 0.40, 95% CI 0.28–0.57). Conclusions: Magnesium sulfate does not appear to affect blood loss intrapartum and postpartum in women with preeclampsia. Magnesium sulfate, therefore, should be continued during CD, given the benefit of seizure prophylaxis without any increased risk of hemorrhage. [ABSTRACT FROM PUBLISHER]

This discussion of Michael Parsons's exposition of the Independent Tradition's clinical theory of technique compares and contrasts the British Independent and American Relational perspectives in regard to their approach to technique. In this discussion I will consider the question whether, given strong object relational influences on relational psychoanalytic theory, we are able to locate systematic differences in the way that Independent and Relational analysts attempt to work, to be with, and to relate to their patients in the psychoanalytic situation. Overlapping historical roots of the two traditions are considered, along with apparent differences in the ways in which the contributions of common ancestors, such as Ferenzci, are applied. I suggest that the integration of American Interpersonal School ideas with Object Relations theory in American Relational Psychoanalysis led to a different therapeutic sensibility, different ways of thinking about and participating in the analytic process from those that are reflected in the Independent Tradition as Dr. Parsons describes it. The discussion includes an imaginative reconsideration of clinical process along relational lines, in an attempt to clarify different emphases in technique between the two schools. [ABSTRACT FROM AUTHOR]

This article has two major purposes. First, we propose a methodology that can help biostatistical reviewers of nonsequential randomized clinical trials, armed only with the single summary statistic from the trial, ask the "what if" question "Could a group sequential design have reached a definitive conclusion earlier?" As a side benefit of this research, four-stage group sequential designs that are optimal in some sense are obtained to serve as reference designs for assessing an actual design against a reasonable alternative design with the same power as the original. Four-stage designs were chosen as a practical limit on the number of stages most practitioners would consider, given the inconvenience of interim analysis, including the need to close studies to accrual while the required follow-up information is collected. Since journal editors and the public can subject the trial to close scrutiny after the fact, this new capability could alter the mind-set of some investigators designing clinical trials. Two real examples that were heavily criticized for staying open too long will be presented. [ABSTRACT FROM AUTHOR]

The article discusses the adaptive dose-ranging designs. The author focuses on several aspects in pharmacology including the objectives of such trials, the decision criteria of each objective, the simulation method and accrual and long-term endpoints. Some recommendations regarding the clinical study of drug development is also presented.

The increasing digitisation of healthcare services has transformed healthcare provision into a data-centric enterprise. Thinking with Joan Tronto and her notion of care, we study medical data practices in the context of a health-tech company developing an algorithmically driven platform to match patients and their physicians with clinical trials. What does it mean to pose the patient in the centre in such a context? In this paper, we show how the enactments of patient-centrism translate to multidimensional enactments of data care for a diversity of domain experts handling medical data, informed by the values and backgrounds of each 'data handler' situated within the concerns of their domain expertise. Where data experts engage solely with the patients' data to facilitate data creation for the platform's algorithmic system, the quest for data quality depends on the preceding practices of care and affective labour about and for the patients. We show how patients get help to torque their medical records and histories into data to fit the demands of the system to ensure access to experimental treatments and clinical trials. We demonstrate how patient-centrism manifests as care for data quality, shaped throughout by differentiated concerns for regulatory compliance. Finally, we argue that regulatory compliance constitutes a care practice across data work that is diversified in its enactments by the experts' domain concerns and backgrounds. [ABSTRACT FROM AUTHOR]

In contemporary exploratory phase of oncology drug development, there has been an increasing interest in evaluating investigational drug or drug combination in multiple tumor indications in a single basket trial to expedite drug development. There has been extensive research on more efficiently borrowing information across tumor indications in early phase drug development including Bayesian hierarchical modeling and the pruning-and-pooling methods. Despite the fact that the Go/No-Go decision for subsequent Phase 2 or Phase 3 trial initiation is almost always a multi-facet consideration, the statistical literature of basket trial design and analysis has largely been limited to a single binary endpoint. In this paper we explore the application of considering clinical priorities of multiple endpoints based on matched win ratio to the basket trial design and analysis. The control arm data will be simulated for each tumor indication based on the corresponding null assumptions that could be heterogeneous across tumor indications. The matched win ratio matching on the tumor indication can be performed for individual tumor indication, pooled data, or the pooled data after pruning depending on whether an individual evaluation or a simple pooling or a pruning-and-pooling method is used. We conduct the simulation studies to evaluate the performance of proposed win ratio-based framework and the results suggest the proposed framework could provide desirable operating characteristics. [ABSTRACT FROM AUTHOR]

This paper focuses on the development and feasibility of a digitally-based educational intervention, titled Recognize & Resist (R&R), for writers of One Direction (1D) fanfiction on Wattpad.com. The goal of R&R is to reduce the prevalence of social norms that are supportive of sexual violence within 1D fanfiction. 1D fanfictions, or fictional romance stories written by fans of this British boy band, have hundreds of millions of views on Wattpad.com. Formative research has found that social norms supportive of sexual violence are prevalent in 1D fanfictions and that some authors have internalized these norms. R&R aims to motivate 1D fanfiction writers to highlight sexual consent and egalitarian gender roles in their writing. To evaluate the intervention’s feasibility, 15 1D fanfiction authors completed a survey and participated in an interview or focus group. Results demonstrate R&R’s feasibility, with high ratings of its acceptability and demand. Insights from the interviews and focus groups provide suggestions for revising R&R before rigorously evaluating its efficacy. Additionally, results demonstrate the utility of using popular culture as a vehicle for attitude-change regarding sensitive health issues. [ABSTRACT FROM AUTHOR]

The benefits of video games in physical education have been extensively researched (Camunas-Vega & Alcaide-Risoto, 2020; Fang et al. 2020). However, little attention has been paid to the effectiveness of commercial video games combined with basketball practice in improving students' reasoning skills (Chuang, Yeh, and Lin 2021; Rogers et al., 2020). In this paper, we present the results of an experimental study whose objective was to assess the effects of a programme that includes the use of a video game as the main learning tool to enhance the reasoning process of secondary education students in Physical Education. A total of 271 students participated in this study. A quasi-experimental pre-post design with a control group was used. The experimental group performed a specific training programme with the NBA 2K16 video game for nine weeks, once a week, 60 min per session. The results show that the students who participated in the programme achieved an improvement in deductive and spatial reasoning with a moderate effect possibly due to the use of a video game. Another conclusion was that sex differences in the spatial and deductive reasoning on the pretest disappeared on the post-test. [ABSTRACT FROM AUTHOR]

AbstractGroup sequential tests have been effective tools in monitoring long term clinical trials. There have been several popular discrete sequential boundaries proposed for modeling interim analysis of clinical trials under the assumption of Brownian motion for the stochastic processes generated from test statistics. In this paper, we study five sequential boundaries under the fractional Brownian motion. The fractional Brownian includes the classic Brownian motion as a special case. We proposed a Bayesian method on how to estimate Hurst parameter, used simulated data to investigate the performance of boundary-based hypothesis-testing under either Bm or fBm assumption in both with and without “treatment effect” scenarios. [ABSTRACT FROM AUTHOR]

The graphical approach has been proposed as a general framework for clinical trial designs involving multiple hypotheses, where decisions are made only based on the observed marginal $$p$$ p -values. The graphical approach starts from a graph that includes all hypotheses as vertices and gradually removes some vertices when their corresponding hypotheses are rejected. In this paper, we propose a reverse graphical approach, which starts from a set of singleton graphs and gradually adds vertices into graphs until rejection of a set of hypotheses is made. Proofs of familywise error rate control are provided. A simulation study is conducted for statistical power analysis, and a case study is included to illustrate how the proposed approach can be applied to clinical studies. [ABSTRACT FROM AUTHOR]

In multi-regional clinical trials, hierarchical linear models have been actively studied because they can reflect that patients in the same region share common intrinsic and extrinsic factors. In this paper, we investigate the statistical properties of the hierarchical linear model including a random effect in the intercept. The big advantage of the random intercept hierarchical linear model is that it can control the type I error rates of testing the overall treatment effect when there are no or clinically negligible regional differences in the treatment effect. Moreover, we compare the pros and cons with the hierarchical linear model in which the random effect is included in the slope. For the two hierarchical linear models, the model selection criteria are determined according to the magnitude of the difference in treatment effect across the regions, and we provide the criteria through simulation studies. [ABSTRACT FROM AUTHOR]

Cannabis misuse and opioid use disorder (OUD) are highly comorbid but under-treated and associated with poorer outcomes. This paper reports a double-blind, parallel-group randomized controlled trial to determine the efficacy of single-session, clinician-delivered screening and brief intervention (SBI) for reducing cannabis risk. The primary outcome was the cannabis-specific Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) scores, measured at three-month post-intervention. The secondary objectives were to determine the efficacy of SBI in reducing the frequency of cannabis use, in risk transition from moderate to low risk, and in prescription and non-prescription opioid use. One hundred forty-three participants were randomly allocated to receive either SBI (n = 72) or control (n = 71) interventions. We performed Per-protocol (PP) (n = 125) and Intention-to-treat (ITT) analysis (n = 143). We adjusted our analysis for age, sex, and baseline ASSIST score. The ITT showed that the SBI group had a significant reduction (F = 39.46, p <.001, Effect size 0.22) in the mean ASSIST at follow-up. PP analyses too revealed a similar positive effect of SBI (F = 53.1; p <.001, Effect size 0.31). At follow-up, the SBI group had a higher number of days of cannabis abstinence. Care providers and policymakers may consider SBI for cannabis use in individuals on medications for OUD. [ABSTRACT FROM AUTHOR]

Provides a brief overview of the skills required to critically and rapidly review a paper in order to determine its academic credibility and worth. Clinical trials; Review paper; Survey paper; Diagnostic or screening tests; Qualitative studies.

In this paper, we discuss a response adaptive randomization method, and why it should be used in clinical trials for rare diseases compared to a randomized controlled trial with equal fixed randomization. The developed method uses a patient’s biomarkers to alter the allocation probability to each treatment, in order to emphasize the benefit to the trial population. The method starts with an initial burn-in period of a small number of patients, who with equal probability, are allocated to each treatment. We then use a regression method to predict the best outcome of the next patient, using their biomarkers and the information from the previous patients. This estimated best treatment is assigned to the next patient with high probability. A completed clinical trial for the effect of catumaxomab on the survival of cancer patients is used as an example to demonstrate the use of the method and the differences to a controlled trial with equal allocation. Different regression procedures are investigated and compared to a randomized controlled trial, using efficacy and ethical measures. [ABSTRACT FROM AUTHOR]

Bayesian methods have been proposed as a natural fit for pediatric extrapolation, as they allow the incorporation of relevant external data to reduce the required sample size and hence trial burden for the pediatric patient population. In this paper we will discuss our experience and perspectives with these methods in pediatric trials. We will present some of the background and thinking underlying pediatric extrapolation and discuss the use of Bayesian methods within this context. We will present two recent case examples illustrating the value of a Bayesian approach in this setting and present perspectives on some of the issues that we have encountered in these and other cases. [ABSTRACT FROM AUTHOR]

Pediatric drug development has many unique challenges, one of which is the evaluation of growth and development changes in children that are expected and are not due to the study intervention. Children grow and mature at different pace. The potential impact of the drug could vary with the developmental age of the participants receiving the treatment. For example, sexual maturation is a critical consideration in children of age 10 and above, but not in younger age groups. How the investigational drug impacts children is ultimately a risk-benefit consideration. In this paper, practical considerations and recommendations are provided on how to assess growth and development based on data collected from clinical trials in pediatric patients. The endpoints and measures related to growth, sexual maturation and neurocognitive development are discussed. Basic analysis approaches are recommended. [ABSTRACT FROM AUTHOR]

In resource poor environments, identifying those most in need of limited available resources is challenging. Kenya's older persons cash transfer programme (OPCT) targeted at the most poor used a 2-stage targeting process to identify beneficiaries, combining community-based selection with a proxy means-test. This paper investigates whether the process "correctly" identified targeted vulnerable older people in Nairobi's informal settlements and whether receipt of the OPCT resulted in an improvement in perceived financial wellbeing. Regression results show that individuals with greater need were covered under the OPCT. Using propensity score matching, the paper evidences that the OPCT improved subjective financial wellbeing among beneficiaries. [ABSTRACT FROM AUTHOR]

This paper investigates the use of a general multi-arm multi-stage (MAMS) approach for time-to-event outcomes that would streamline simultaneous comparison of a large number of promising therapies in clinical trials, thus significantly reducing the time and the number of patients needed to evaluate the treatment. Controlling type I error in this setting is different than regular clinical trials as this approach incorporates both multiple comparison between arms and multiple stages. Historically, pairwise (PWER) and familywise (FWER) type I error rates have been primarily used to regulate the type I error in such designs. This paper will focus on constructing the efficacy and futility boundaries for a MAMS clinical trial in two different scenarios. In the first, it is assumed that the same outcome is used throughout the clinical trial for both intermediate and final assessments. In this scenario, we propose using the generalized Dunnett procedure that controls FWER. In the latter scenario, where intermediate and final outcomes are different in nature, we propose modifications to the existing method that originally concentrated on controlling PWER and extend the method to include FWER in the design. We also explore the performance of the proposed MAMS design in a setting where the proportional hazard assumption is violated in the presence of a delayed treatment effect and demonstrate the loss of power because of that. An alternative test statistic that can help circumvent this problem to maintain the desired power is also suggested. [ABSTRACT FROM AUTHOR]

Methods to extend the strong internal validity of randomized controlled trials to reliably estimate treatment effects in target populations are gaining attention. This paper enumerates steps recommended for undertaking such extended inference, discusses currently viable choices for each one, and provides recommendations. We demonstrate a complete extended inference from a clinical trial studying a pharmaceutical treatment for Alzheimer's disease (AD) to a realistic target population of European residents diagnosed with AD. This case study highlights approaches to overcoming practical difficulties and demonstrates limitations of reliably extending inference from a trial to a real-world population. [ABSTRACT FROM AUTHOR]

Introduction/Aims. Primary lateral sclerosis (PLS) is exceedingly rare and has been an enigmatic disease. Recent progress has drastically changed this perception, with early biomarkers being investigated and potential medications for PLS emerging at the preclinical stage. The aim of this paper is to describe a study of PLS natural history and discuss the limitations and proposed solutions to the study of a rare and slowly progressive disease. Methods. The PLS Natural History Study is a 30-site, 24-month, prospective study that is supported by multiple funding sources. The study aims to enroll 50 early PLS (disease duration ≤4 years) and 50 definite PLS (disease duration 4 to 15 years) participants using modified PLS Diagnostic Criteria. Smartphone-based assessments including semi-quantitative and quantitative measures and patient-reported outcomes are utilized. In-person quantitative measures are also completed during site visits. The change in the PLS Functional Rating Scale score is the primary outcome. The study utilizes the NeuroBANK® patient-centric data capture and management platform. The biostatistical analysis plan has been developed. Results. In one year, 28 participants have been recruited. Enrollment has been much slower than anticipated due to the COVID-19 pandemic, the rarity of PLS, and potential study competition for internal resources from ALS clinical trials. Discussion. We discuss the need for more innovative methods to enroll and study individuals with such rare diseases and propose a number of mechanisms by which more efficient enrollment could be facilitated. [ABSTRACT FROM AUTHOR]

Over the past decades, the primary interest in vaccine efficacy or immunogenicity evaluation mostly focuses on the biological effect of immunization in complying with the vaccination schedule in a targeted population. The safety questions, which are essential for vaccines as they are generally given to large healthy populations, need to be clearly defined to reflect the risk assessment of interest. ICH E9 (R1) provides a structured framework to clarify the clinical questions and formulate the treatment effect as an estimand. This paper applies the estimand framework to vaccine clinical trials on common clinical questions regarding efficacy, immunogenicity, and safety. [ABSTRACT FROM AUTHOR]

ICH E9(R1) introduces the estimand framework to strengthen dialogues between sponsors and regulators during drug development. A well-structured benefit-risk assessment (BRA) framework also intends to facilitate communication among stakeholders. However, the estimand in ICH E9(R1) is written mainly from the perspective of a single measure of treatment effect in clinical trials. There is lack of systematic discussion on estimand in the context of BRA. This paper initiates the BRA discussion under the estimand framework. By identifying two types of BRA approaches, we summarize and discuss completed clinical trials, using the estimand language for BRA. Benefits and challenges of using estimand for BRA are also discussed. [ABSTRACT FROM AUTHOR]

Returning to baseline (RTB) has been a practical method for handling missing data. Here we consider longitudinal clinical trials with daily patient reported outcomes (PROs), where efficacy endpoints are often defined as the average daily values in a cycle (such as a month or a week). The conventional method treats data at cycle level and ignores daily values. In this paper, we build a two-level constrained longitudinal data analysis (cLDA) model on daily values and propose two-level RTB method to impute daily values. Standard multiple imputation (MI) approach and likelihood-based approach are proposed and evaluated by simulations. [ABSTRACT FROM AUTHOR]

This paper explores the use of a smartphone within a therapy. It describes its use as a screen object in the service of survival-oriented infantile omnipotence, towards its use as a bridge that facilitated the structuring of internal space and the emergence of nascent capacities for relatedness and introspection. Clinical material from a ten year-long therapy with an adopted girl illustrates the presence of the smartphone on three layers of the therapeutic relationship. First, on a sensory level, the smartphone was used as an almost autistic screening object, but also as an auditory-visual envelope where therapist and patient could be immersed together. Second, on the level of patient-therapist communication and transference relations, the use of the smartphone revived infantile trauma involving the internalisation of a parental gaze that established a distorted internal and external gaze experience, which I termed 'psychic cross-eyes'. Third, the smartphone served as a 'third' object that helped establish our shared observation of reality, and of the patient's own psyche. By dwelling together, and developing a private language of 'being-with' 'inside' the phone, while gradually interpreting primitive anxieties and defences in terms of withdrawal from relatedness, we were able to add greater flexibility to the patient's notion of relatedness, establish her binocular vision, and promote the development of the inner witness function. The paper thus explores the smartphone's transition from a sterile, screening object, to a communicative, 'object-seeking' presence. [ABSTRACT FROM AUTHOR]

The paper describes a deceptive kind of autistic encapsulation, charact-erised by pseudo-internal space and distortions in the normal development of psychophysical space. It introduces the metaphor of loops as spatial-temporal organisations that illuminate three aspects of autistic encapsulation, two of which were first described by Frances Tustin. Three types of loops – simple, twisted and double-twisted – are explored. The paper delineates the double-twisted loop as an additional and more complex manifestation, typical to post-autistic organisation. Here, symbolic thinking and communication function as a disguise, obscuring the child's trajectory on an infinite continuum that folds around itself, thus denying the potential for separateness and preventing the accumulative realisation of mental space. Using two clinical vignettes, the author shows how such a presentation leaves the therapist in danger of being tempted by the child's pseudo-internal world, while remaining dissociated from their developmental needs. [ABSTRACT FROM AUTHOR]

Addressing respect, gender equity and gender-based violence in schools has a long history. Renewed government efforts to address gender-based violence in schools through a whole school approach have commenced under the umbrella 'respectful relationships education'. The research presented in this paper is nestled within a larger project aimed to evaluate the implementation and impact of a whole school approach to respectful relationships education across two Australian states (Our Watch, forthcoming). The purpose of this paper is to examine the effects of a six-month respectful relationships education program on the gender awareness and bias of early primary school students. Using a single group pre-post test research design, students from two primary schools in Australia completed a survey before (n = 202) and after (n = 217) completion of a respectful relationships education pilot program. A modified version of the Children's Occupation, Activities, and Traits-Attitudes Measure (COAT-AM; Liben and Bigler, 2002) and the Children's Occupation, Activities, and Traits-Personal Measure (COAT-PM; Liben and Bigler, 2002) were used to assess students' views about gender. After the pilot, boys and girls were significantly less likely to consider stereotypically masculine occupations and activities as only for boys and stereotypically feminine occupations and activities as only for girls. Results indicate that ongoing respectful relationships education could be an effective way to disrupt gender stereotyping in early primary school students. [ABSTRACT FROM AUTHOR]

This paper proposes a framework for studying the potential of museum-led interventions for supporting stroke rehabilitation goals. The intervention was based on Kirvevold et al.'s model for interventions for post-stroke wellbeing. Mixed-methods data wqas collected to review benefits in a pilot study, including retrospective video observations for six sessions with four patients; interviews with patients, carers and facilitators; pre-post patient assessments; and facilitator diaries. Systematic analysis of videos showed high levels of concentration and engagement with museum objects, low levels of social interaction, and positive or neutral mood throughout. Thematic qualitative analysis suggested patients felt engaged in meaningful activities, which lifted negative mood, provided positive distraction from the ward, and increased self-esteem, including belief in patient abilities. Further research is needed to fully establish the potential of museum-led interventions for stroke rehabilitation. [ABSTRACT FROM AUTHOR]

Clustered data frequently occur in biomedical research fields and clinical trials. The log-rank tests are widely used for two-independent samples of clustered data tests. The randomized block design and truncated binomial design are used for forcing balance in clinical trials and reducing selection bias. In this paper, survival clustered data are randomized by generalized randomized block, and subsequently clustered data in each block are randomized by truncated binomial design. Consequently, the p-values of the null permutation distribution of log-rank tests for clustered data are approximated via the double saddlepoint approximation method. Comprehensive numerical studies are carried out to assess the accuracy of the saddlepoint approximation. This approximation has a great accuracy over the asymptotic normal approximation. [ABSTRACT FROM AUTHOR]