The effects of person-centred active rehabilitation on symptoms of suspected Chronic Traumatic Encephalopathy: A mixed-methods single case design.

OBJECTIVE: The objective was to investigate the effectiveness of a person-centred active rehabilitation programme on symptoms associated with suspected Chronic Traumatic Encephalopathy (CTE). This was accomplished by (1) assessing the effect that a person-centred active rehabilitation programme had on participant symptoms, and (2) exploring how temporal contextual factors affected the participants' experience with, and perceived effectiveness of, the active rehabilitation programme. METHODS: A twelve-month mixed-methods single case experimental research design was used with six cases (participants). Individual cases were involved in a 51-week study period including an initial interview and three-week baseline phase. Cases were then randomly allocated to one of two n-of-1 study designs (i.e., A-B, B-A, B-A, A-B or B-A, A-B, A-B, B-A) where A and B represent a non-intervention and intervention phase, respectively. Interviews were conducted regularly throughout the study whilst outcome measures were assessed at each follow-up. Analysis of the data included visual, statistical, and qualitative analysis. RESULTS: Visual and statistical analysis of cognitive and executive function, and mindful attention, demonstrated trivial-to-large effects with the summary reflecting positive or unclear results. A mixed picture was observed for mood and behaviour with effects considered trivial-to-large, and the summary demonstrating positive, unclear and negative effects. Qualitative analysis indicated a perceived improvement in outcome measures such as memory, attention, anxiety, and emotional control despite mixed quantitative findings whilst a clear impact of contextual factors, such as COVID-19, the political atmosphere, exercise tolerance, programme progression, and motivation were evident during the intervention. CONCLUSIONS: This study has provided primary-level evidence to suggest active rehabilitation as a potential intervention for the management of suspected CTE symptoms. This study has also demonstrated the benefit of a person-centred approach to both clinical research and practice, particularly by considering contextual factors for a better understanding of an intervention effect.

Effect of digital game intervention on cognitive functions in older adults: a multiple baseline single case experimental design study.

BACKGROUND: Residents in nursing homes are prone to cognitive decline affecting memory, visuospatial cognition, and executive functions. Cognitive decline can lead to dementia, necessitating prioritized intervention. METHODS: The current study aimed to investigate whether an intervention using a digital game was effective for preserving and improving the cognitive function of residents in nursing homes. An intervention study was conducted using a single-case AB design with multiple baselines. The participants in the study were five older adults aged 65 and over who do not play digital games regularly. The study ran for 15 weeks, including a baseline (phase A) and an intervention phase (phase B). Phase A had five baselines (5 to 9 weeks) with random participant assignment. In phase B, participants engaged in a digital game (Space Invaders) individually. Cognitive function was assessed as the outcome, measured using the Brain Assessment (performed on a tablet through the Internet) at 16 measurement points. Four of five participants (two female and two male) were included in the analysis, using visual inspection and Bayesian statistics with multi-level modeling. RESULTS: Visual inspection of the graphs revealed cognitive function score improvements after the intervention for most layers in terms of memory of numbers, memory of words, mental rotation test (visuospatial ability), and total scores in the Brain Assessment. These effects were also significant in the analysis by multi-level modeling. CONCLUSIONS: The results suggest that the use of digital games may be effective for preserving and improving cognitive function among residents of nursing home. TRIAL REGISTRATION: This study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000048677; public title: Effect of a Digital Game Intervention for Cognitive Functions in Older People; registration date: August 30, 2022).

Highly sensitive serum volatolomic biomarkers for pancreatic cancer diagnosis.

The discovery of new diagnostic tools for the early detection of diseases with poor prognosis such as pancreatic adenocarcinoma (PAC) is of high importance. The results from a control-case study (20 PAC patients, 19 healthy controls) for the search of new biomarkers of pancreatic cancer based in differences in the serum volatolome are presented in this work. Volatolomics were performed following a non-targeted HS-SPME-GC/MS approach, and a total of 433 volatile organic compounds (VOCs) was detected in the human serum samples. Of these, 125 VOC indexes showed a significant variation when controls and patients were compared (p-value < 0.05). Bonferroni corrected p-values < 0.05 were found for 40 features. PCA analysis showed the control-PAC discrimination capability of VOCs in serum, and PLS-DA was performed to select the best candidate biomarkers for the diagnosis of PAC. For the 40 selected VOCs, calculated areas under the curve (AUC) ranged from 0.98 to 0.85, and 11 of them were successfully validated using an independent set of samples (5 PAC patients, 5 healthy controls). Four of the proposed PAC biomarkers were identified as toluene, 2-ethyl-1-hexanol, pentylbenzene, and butoxymethylbenzene. Combinations of the identified PAC biomarkers were tested and showed AUC > 0.90, with the more promising candidate being butoxymethylbenzene (AUC = 0.98).

Multilevel modeling in single-case studies with zero-inflated and overdispersed count data.

Count outcomes are frequently encountered in single-case experimental designs (SCEDs). Generalized linear mixed models (GLMMs) have shown promise in handling overdispersed count data. However, the presence of excessive zeros in the baseline phase of SCEDs introduces a more complex issue known as zero-inflation, often overlooked by researchers. This study aimed to deal with zero-inflated and overdispersed count data within a multiple-baseline design (MBD) in single-case studies. It examined the performance of various GLMMs (Poisson, negative binomial [NB], zero-inflated Poisson [ZIP], and zero-inflated negative binomial [ZINB] models) in estimating treatment effects and generating inferential statistics. Additionally, a real example was used to demonstrate the analysis of zero-inflated and overdispersed count data. The simulation results indicated that the ZINB model provided accurate estimates for treatment effects, while the other three models yielded biased estimates. The inferential statistics obtained from the ZINB model were reliable when the baseline rate was low. However, when the data were overdispersed but not zero-inflated, both the ZINB and ZIP models exhibited poor performance in accurately estimating treatment effects. These findings contribute to our understanding of using GLMMs to handle zero-inflated and overdispersed count data in SCEDs. The implications, limitations, and future research directions are also discussed.

Intrathecal magnesium delivery for Mg++-insensitive NMDA receptor activity due to GRIN1 mutation.

BACKGROUND: Mutations in the NMDA receptor are known to disrupt glutamatergic signaling crucial for early neurodevelopment, often leading to severe global developmental delay/intellectual disability, epileptic encephalopathy, and cerebral palsy phenotypes. Both seizures and movement disorders can be highly treatment-refractory. RESULTS: We describe a targeted ABA n-of-1 treatment trial with intrathecal MgSO4, rationally designed based on the electrophysiologic properties of this gain of function mutation in the GRIN1 NMDA subunit. CONCLUSION: Although the invasive nature of the trial necessitated a short-term, non-randomized, unblinded intervention, quantitative longitudinal neurophysiologic monitoring indicated benefit, providing class II evidence in support of intrathecal MgSO4 for select forms of GRIN disorders.

Comentario acerca del caso Belcebú / Commentary on the Beelzebub case / Commentaire sur le cas clinique de Belzébuth / Comentário sobre o caso Belzebu

A partir de la presentación del caso clínico de un niño de 10 años llamado Belcebú, atendido durante la pandemia de forma virtual a lo largo de un año y cuatro meses, se realiza un comentario teórico-clínico puntualizando los aspectos vinculados a:los enunciados identificatorios; el niño en la estructura familiar y, como aspecto más relevante, el lugar del juego producido en las sesiones, el que sostenido por la mirada posibilitadora de la analista, le permitió alniño elaborar y rescribir marcas identitarias,en pos de una subjetivación menos tanática AU

Based on the presentation of the clinical case of a 10-year-old boy named Belcebú, treated virtually during the pandemic for a yearand four months, a theoretical-clinical comment is made, pointing out the aspects related to: the identifying statements; the child in the family structure and, as a most relevant aspect, the place of the play produced in the sessions, which, supported by the analyst's enabling gaze, allowed the child to elaborate and rewrite identity marks, in pursuit of a less thanatic subjectivation AU

Sur la base de la présentation du cas clinique d'un garçon de 10 ans nommé Belcebú, traité virtuellement pendant la pandémie durant un an et quatre mois, un commentaire théorico-clinique est fait, soulignant les aspects liés:aux énoncés identifiants; l'enfant dans la structure familiale et, comme aspect le plus pertinent, la place du jeu produit dans les séances, qui, soutenu par le regard habilitant de l'analyste, a permis à l'enfant d'élaborer et de réécrire des marques identitaires, à la poursuite d'une subjectivation moins thanatique AU

A partir da apresentação do caso clínico de um menino de 10 anos chamado Belcebú, tratado virtualmente durante a pandemia por um ano e quatro meses, é feito um comentário teórico-clínico, apontando os aspectos relacionados: a os depoimentos identificadores; a criança na estrutura familiar e, como aspecto mais relevante, o lugar da brincadeira produzida nas sessões, que, amparada pelo olhar capacitador do analista, permitiu à criança elaborar e reescrever marcas identitárias, em busca de uma subjetivação menos tanática AU

Individualized Studies of Triggers of Paroxysmal Atrial Fibrillation: The I-STOP-AFib Randomized Clinical Trial.

Importance: Atrial fibrillation (AF) is the most common arrhythmia. Although patients have reported that various exposures determine when and if an AF event will occur, a prospective evaluation of patient-selected triggers has not been conducted, and the utility of characterizing presumed AF-related triggers for individual patients remains unknown. Objective: To test the hypothesis that n-of-1 trials of self-selected AF triggers would enhance AF-related quality of life. Design, Setting, and Participants: A randomized clinical trial lasting a minimum of 10 weeks tested a smartphone mobile application used by symptomatic patients with paroxysmal AF who owned a smartphone and were interested in testing a presumed AF trigger. Participants were screened between December 22, 2018, and March 29, 2020. Interventions: n-of-1 Participants received instructions to expose or avoid self-selected triggers in random 1-week blocks for 6 weeks, and the probability their trigger influenced AF risk was then communicated. Controls monitored their AF over the same time period. Main Outcomes and Measures: AF was assessed daily by self-report and using a smartphone-based electrocardiogram recording device. The primary outcome comparing n-of-1 and control groups was the Atrial Fibrillation Effect on Quality-of-Life (AFEQT) score at 10 weeks. All participants could subsequently opt for additional trigger testing. Results: Of 446 participants who initiated (mean [SD] age, 58 [14] years; 289 men [58%]; 461 White [92%]), 320 (72%) completed all study activities. Self-selected triggers included caffeine (n = 53), alcohol (n = 43), reduced sleep (n = 31), exercise (n = 30), lying on left side (n = 17), dehydration (n = 10), large meals (n = 7), cold food or drink (n = 5), specific diets (n = 6), and other customized triggers (n = 4). No significant differences in AFEQT scores were observed between the n-of-1 vs AF monitoring-only groups. In the 4-week postintervention follow-up period, significantly fewer daily AF episodes were reported after trigger testing compared with controls over the same time period (adjusted relative risk, 0.60; 95% CI, 0.43- 0.83; P < .001). In a meta-analysis of the individualized trials, only exposure to alcohol was associated with significantly heightened risks of AF events. Conclusions and Relevance: n-of-1 Testing of AF triggers did not improve AF-associated quality of life but was associated with a reduction in AF events. Acute exposure to alcohol increased AF risk, with no evidence that other exposures, including caffeine, more commonly triggered AF. Trial Registration: ClinicalTrials.gov Identifier: NCT03323099.

Adaptive single case design (ASCD): a model for education, training, and assessment / Estudo de caso único adaptado (ASCD): um modelo para educação, treinamento e avaliação

Aims: single case designs (SCDs) can help us understand change in learning-related variables, such as knowledge and skill, at the level of an individual learner, at the level of a team or group of learners, or at the level of a situation or system. Adaptive single case design (ASCD) is a new model that integrates (i.) elements of methods of education, training, and assessment that, through research methods other than SCDs, have received solid empirical evidence in the research literature and (ii.) principles of SCDs that can facilitate the integration of research in everyday practice. The rationale behind ASCD is to allow rapid evidence-based decision making in the practice of education, training, and assessment, at the unit of analysis ­ individual, group, team, situation, or system ­ that is considered appropriate in the context at hand. Method: an ASCD algorithm is introduced and discussed in the context of change at the level of the individual, change in a group or team, and change in a situation or system. Results: ASCD can be used to understand change at each of the previously mentioned units of analysis at any number of units including a single unit (one individual, one team, or one situation or system), and this change can be used for research purposes as well. Conclusion: ASCD enables both evidence-based practical decision making and research without stringent demands on the number of learners, groups, teams, situations, or systems.

Objetivos: estudos de caso único podem nos ajudar a entender a mudança nas variáveis relacionadas ao aprendizado, como conhecimento e habilidade, no nível de um aluno individual, no nível de uma equipe ou grupo de alunos, ou no nível de uma situação ou sistema. O Estudo adaptativo de caso único (ASCD) é um novo modelo que integra (i.) elementos de métodos de educação, treinamento e avaliação que, por meio de métodos de pesquisa que não sejam estudos de caso único, receberam evidências empíricas sólidas na literatura de pesquisa e (ii.) princípios de estudos de caso único, que podem facilitar a integração da pesquisa na prática cotidiana. A lógica por trás do ASCD é permitir a rápida tomada de decisão baseada em evidências na prática da educação, treinamento e avaliação, na unidade de análise ­ individual, grupo, equipe, situação ou sistema ­ que é considerada apropriada no contexto em questão. Método: um algoritmo ASCD é introduzido e discutido no contexto de mudança no nível do indivíduo, mudança em um grupo ou equipe e mudança em uma situação ou sistema. Resultados: o ASCD pode ser usado para entender a mudança em cada uma das unidades de análise mencionadas anteriormente em qualquer número de unidades, incluindo uma única unidade (um indivíduo, uma equipe ou uma situação ou sistema), e para fins de pesquisa. Conclusão: o ASCD permite a a pesquisa e a tomada de decisão prática baseada em evidências, sem demandas rigorosas sobre o número de alunos, grupos, equipes, situações ou sistemas.

Benefits of 1-Yr Home Training With Functional Electrical Stimulation Cycling in Paraplegia During COVID-19 Crisis.

ABSTRACT: The purpose of this observational study was to report the experience of a 1-yr home training with functional electrical stimulation cycling of a person with T4 American Impairment Scale A paraplegia for 9 yrs, homebound due to the COVID-19 health crisis. The 40-yr-old participant had a three-phase training: V1, isometric stimulation; V2, functional electrical stimulation cycling for 3 sessions/wk; and V3, functional electrical stimulation cycling for 2-4 sessions/wk. Data on general and physical tolerance, health impact, and performance were collected. Borg Scale score relating to fatigue was 10.1 before training and 11.8 after training. The average score for satisfaction at the end of sessions was 8.7. Lean leg mass increased more than 29%, although total bone mineral density dropped by 1.6%. The ventilatory thresholds increased from 19.5 to 29% and the maximum ventilatory peak increased by 9.5%. Rosenberg's Self-esteem Scale score returned to its highest level by the end of training. For the only track event on a competition bike, the pilot covered a distance of 1607.8 m in 17 mins 49 secs. When functional electrical stimulation cycling training is based on a clear and structured protocol, it offers the person with paraplegia the opportunity to practice this activity recreationally and athletically. In times of crisis, this training has proven to be very relevant.

Establishment of Three Types of Immortalized Human Skin Stem Cell Lines Derived from the Single Donor.

Currently, human-skin derived cell culture is a basic technique essential for dermatological research, cellular engineering research, drug development, and cosmetic development. But the number of donors is limited, and primary cell function reduces through cell passage. In particular, since adult stem cells are present in a small amount in living tissues, it has been difficult to obtain a large amount of stem cells and to stably culture them. In this study, skin derived cells were isolated from the epidermis, dermis, and adipose tissue collected from single donor, and immortalization was induced through gene transfer. Subsequently, cell lines that could be used as stem cell models were selected using the differentiation potential and the expression of stem cell markers as indices, and it was confirmed that these could be stably cultured. The immortalized cell lines established in this study have the potential to be applied not only to basic dermatological research but also to a wide range of fields such as drug screening and cell engineering.

Does amantadine maintain function in long-established brain injury? A single case experimental design.

OBJECTIVE: The role of dopamine agonist (DA) in restoring consciousness and cognition in recovery phase following acquired brain injury (ABI) is established (1-5). The role in later recovery is less well defined. We report a single case experimental design (SCED) trial of amantadine demonstrating improvement in function, six years following ABI. METHOD: A scoring system based on established abilities in personal care and interaction was used to identify tasks with component actions, 34 actions in total, each ranked in terms of quality of response to a request or prompt. Actions were scored on maintenance dose amantadine; on withdrawal; and after reintroduction. Daytime sleep duration was also recorded. RESULTS: At 3rd and 5th weeks post withdrawal, deterioration was noted in 27 of 34 graded activities. At 3rd and 5th weeks following reintroduction, all but 3 grades returned to baseline or better. Afternoon sleep duration increased from 35 to 80 minutes during withdrawal period returning towards baseline on amantadine resumption. CONCLUSION: We believe this provides evidence for benefit of amantadine in sustaining function following ABI. The SCED model used provides a template for others to use to identify comparable change in similar trials.

Prostate permanent implant brachytherapy with BARC I-125 Ocu-Prosta seeds.

AIM: The aim of this study is implementation and establishment of standard operating procedure for permanent prostate implant brachytherapy technique using BARC I-125 Ocu-Prosta seeds. MATERIALS AND METHODS: The transrectal ultrasound (US)-guided procedure was used for permanent implant procedure. The Best® Sonalis™ US Imaging System and Best NOMOS™ Treatment Planning system was used for volume study and implant procedure. The BARC provided I-125 Ocu-Pro radioactive seeds were implanted into the patient with help of Mick@ Applicator. The implant was performed based on pre-implant dosimetry and intraoperative planning performed during implant procedure. RESULTS: The necessary quality assurance tests were performed for US system before clinical use. The boost dose of 110 Gy was prescribed to the prostate volume of 34.71 cc. About 48 seeds with activity of 0.35 mCi (each) implanted into the prostate volume with reference to intraoperative planning. At the end of procedure, the patient underwent abdomen fluoroscopic examination, to ensure the seed counts in the prostate volume. The day after the implant, the patient was discharged. One month later a planning computed tomography and treatment planning was performed for seed position and dose verification. CONCLUSIONS: Low dose rate permanent implant brachytherapy has the advantage of being a one-time procedure and the existing long term follow-up supports its excellent outcome and low morbidity. BARC-BRIT is supplying the loose 125I seeds. These seeds can be easily implanted into the patient using Mick applicator. However, the pre-implant seed preparation and implant procedure may result some radiation exposure to staff involved. The radiation dose can be minimized with good practice. This report is one patient pilot study and intended to test the implant systems and standard operative procedure henceforth for permanent implant brachytherapy procedure.

A preliminary investigation of a novel method to manipulate penis length to measure female sexual satisfaction: a single-case experimental design.

OBJECTIVES: To investigate a novel methodology and explore whether artificially reducing the depth of penetration during intercourse matters to women. STUDY DESIGN AND METHODS: A study with a single-case experimental design ('n of 1'), in which a heterosexual couple act as their own control and the study is then replicated in subsequent couples, was conducted. Thirty-five couples were assessed for eligibility to participate. Twenty-nine couples without any sexual problems were randomized and 12 submitted sufficient data to analyse. As a proxy for reducing penis length, we artificially reduced the depth of penetration by using different sizes of silicone rings around the base of the man's erect penis. The main outcome measures were provided by the female partner on a scale of 0-100 and comprised: degree of (i) overall sexual pleasure; (ii) sexual pleasure from intercourse alone; and (iii) emotional connection to the male partner. The female partner was also asked before the experiment began to rate the degree of positive or negative change that would be personally meaningful for her. RESULTS: On average, reducing the depth of penetration led to a statistically significant 18% reduction of overall sexual pleasure with an average 15% reduction in length of the penis. The longer the erect penis, the less likely the rings were to have an impact on sexual pleasure. There was a range of individual responses, however, with a minority of women reporting that reducing the depth of penetration was more pleasurable on some occasions. CONCLUSIONS: Size may matter in women in a healthy stable relationship when there is penile shortening. Because of the small number of couples and the inclusion of men with an apparently long penis, our results are preliminary, and we welcome replication in a larger sample with a more diverse range of penile lengths. Our results should not be misinterpreted as meaning that increasing penile length will increase sexual pleasure in women.

Intense Pulsed Light: A Methodical Approach to Understanding Clinical Endpoints.

BACKGROUND: Intense Pulsed Light (IPL) is a non-coherent polychromatic broadband filtered flashlamp that emits light in the spectrum of approximately 400–1200 nm. Its effects on photorejuvenation are well documented. The goal of this study is to help practitioners better conceptualize and fine tune IPL device settings in order to produce the most effective and safest clinical outcome. MATERIALS/METHODS: This was a prospective study testing several filters (515 nm; 560 nm; 590 nm and 530–650; 900–1200 nm vascular filter), fluences, pulse durations, and pulse numbers (ie, multiple sequence pulsing or MSP) with a new IPL system. RESULTS: Post-procedure erythema response was more pronounced with increasing fluence, decreasing wavelength, fewer pulses and shorter pulse duration. The exception was the 515 nm filter with regard to pulse duration, which was observed to have a more pronounced response with longer pulse durations. The overall clinical outcome at the 4-week follow-up visit demonstrated greatest improvement in erythema and pigmentation using the 515 nm filter on a Fitzpatrick Skin Type III individual. CONCLUSION: Greatest clinical endpoint response at 4-week follow-up was observed with more robust initial responses. This was most apparent at higher fluence levels and fewer pulse counts. However, when the IPL is pushed to aggressive parameters, there is risk of hypopigmentation and hair loss as seen in this case study. Skin type is an important consideration when using IPL and MSP adds to its safety profile. J Drugs Dermatol. 2021;20(2):203-207. doi:10.36849/JDD.5638.

Bayesian Analysis for Multiple-baseline Studies Where the Variance Differs across Cases in OpenBUGS.

Objective: There is a growing interest in the potential benefits of applying Bayesian estimation for multilevel models of SCED data. Methodological studies have shown that Bayesian estimation resolves convergence issues, can be adequate for the small sample, and can improve the accuracy of the variance components. Despite the potential benefits, the lack of accessibility to software codes makes it difficult for applied researchers to implement Bayesian estimation in their studies. The purpose of this article is to illustrate a feasible way to implement Bayesian estimation using OpenBUGS software to analyze a complex SCED model where within-participants variability and autocorrelation may differ across cases. Method: By using extracted data from a published study, step-by-step guidance in analyzing the data using OpenBUGS software is provided, including (1) model specification, (2) prior distributions, (3) data entering, (4) model estimation, (5) convergence criteria, and (6) posterior inferences and interpretations. Result: Full codes for the analysis are provided.