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Design and Procedure
GIST
The study was approved by the ethics committee of the Max Planck Institute for Human Development and the University of Granada. Participants were provided with information about the frequency of benefits and side effects of 3 painkilling medications (i.e., aspirin, ibuprofen, and paracetamol) in comparison with a place...
PMC10625725
Measures
All knowledge questions as well as subjective ratings were previously used by Gaissmaier et al.
PMC10625725
Gist knowledge
GIST
Gist knowledge reflects the essential understanding of the information and was assessed with 5 qualitative questions that were nonnumerical and asked for ordinal comparisons between the painkillers (e.g., “Which drug caused side effects least frequently?”“Which painkiller was worst overall?”). To answer these questions...
PMC10625725
Verbatim knowledge
Verbatim knowledge reflects the precise quantitative understanding and was assessed with 8 quantitative questions that asked for numerical statements and comparisons. To answer those questions, participants needed to read off frequencies from the information chart (e.g., “How many patients experience side effects with ...
PMC10625725
Accessibility
Subjective accessibility of the information was assessed with 5 questions, each of which could be answered on a 5-point scale ranging from 1 (
PMC10625725
Attractiveness
Subjective attractiveness of the representation was assessed with 8 questions, each of which could be answered on a 5-point scale ranging from 1 (
PMC10625725
Graph literacy
We assessed graph literacy using the Spanish translation of the Graph Literacy Scale. The scale assesses an individual’s knowledge of health-related information based on graphical representations with 13 items on 3 levels of difficulty: reading the data (i.e., finding the specific information on a graph; 4 items), read...
PMC10625725
Numeracy
We assessed numeracy as a control variable, because it is correlated with graph literacy (in our sample:
PMC10625725
Participants
One hundred sixty participants (80 in each of the conditions “choice” and “no choice”) were included in the study that comprised working with the materials (T1) and the recall test (T2). All participants were students at the University of Granada, Spain, and they received course credit for participation. The sample inc...
PMC10625725
Results
The data and analysis script for this study are openly available at
PMC10625725
Participant Characteristics
As presented in Participant Characteristics and Descriptive Statistics for Conditions “No Choice” and “Choice”This percentage is based on
PMC10625725
What Is Chosen Predominantly, and Who Chose Graphs Rather than Numbers?
We first checked whether participants in the “choice” condition were more likely to choose one of the representations by comparing the actual choice proportions with a 50/50 split, using a binomial test. Participants were generally more likely to choose the graphical representation than the numerical one. Of the 80 par...
PMC10625725
Does Choice Foster Knowledge?
GIST
To analyze whether knowledge differed between the “no choice” and the “choice” condition, we ran a linear mixed-effects model with random intercepts for participants. The outcome variable was knowledge and the predictors were time (T1 v. T2; effect-coded as T1 = −0.5, T2 = +0.5) and knowledge type (verbatim v. gist; ef...
PMC10625725
Effects of graph literacy and numeracy
People higher in graph literacy had overall higher knowledge (high:
PMC10625725
Effects of choice
GIST
In contrast to our expectations, choice did not generally improve knowledge (choice: Choice did, however, specifically increase verbatim knowledge (choice: Interestingly, in contrast to (our default) placebo scoring, if we scored gist knowledge with medication-only scoring, choice increased overall knowledge (choice:
PMC10625725
Effects of representation (numerical, graphical) and its interaction with graph literacy
Participants who worked with numbers were overall better than those who worked with graphs (numbers:
PMC10625725
Does Choice Increase Ratings of Accessibility and/or Attractiveness?
REGRESSION
To analyze whether accessibility and attractiveness differed between the “no choice” and “choice” condition, we ran 2 separate linear regression models with accessibility and attractiveness as outcome variables, respectively; the predictors were condition (“no choice” v. “choice”; effect coded), representation (numbers...
PMC10625725
Discussion
GIST
Not everyone benefits from graphical representations of statistical information, and for some people, numerical representations are actually better suited to foster knowledge.We were first asking which representation gets chosen more often and whether people chose representations in line with underlying skills, particu...
PMC10625725
Limitations
≈0.72
Several limitations of the study need to be taken into consideration when interpreting the results. First, the sample consisted of a diverse yet highly educated group of students who are not representative of the general population in Spain. Consequently, they have higher graph literacy scores than an average person ra...
PMC10625725
Conclusion
comprehension and recall of medical information, comprehension and recall
MINOR
People differ in which kind of representation of statistical information they understand best: Some people understand graphical representations better, others are better off with mere numbers. Yet assessing their abilities to understand graphical and numerical information is infeasible in practice. Giving patients the ...
PMC10625725
Supplemental Material
PMC10625725
References
PMC10625725
Introduction
Non-medical use of psychostimulants is common in healthy subjects, often for enhancing cognitive performance in domains such as memory or vigilance ([see Inconsistent results have been found for amphetamine on working memory (WM) [Caffeine is also a psychostimulant that is widely consumed worldwide for its psychomotor ...
PMC10343048
Methods and materials
PMC10343048
Ethical approval
The University of Western Australia (UWA) Human Research Ethics Committee has granted ethical approval for this study (RA/4/1/8056 for experiment 1 and RA/4/20/4558 for experiment 2). The study is registered at the Australian New Zealand Clinical Trials Registry (ACTRN12608000610336, for experiment 1 and ACTRN126180012...
PMC10343048
Participant recruitment
substance-use, schizophrenia-spectrum, first-degree, cardiovascular disorder, word of mouth, ADHD, schizophrenia, psychotic disorders, bipolar affective disorder, neurological illness
CARDIOVASCULAR DISORDER, SEPARATION, SYMPATHOMIMETIC
All forty participants were recruited by word of mouth, lecture announcements, advertisements on campus notice boards, social media, or university-group emails in 2017 and 2018. Participants were informed to abstain from any psychoactive substance (including caffeine) at least 24 hours before the test.Inclusion criteri...
PMC10343048
CONSORT 2010 Flow Diagram 1.
PMC10343048
CONSORT 2010 Flow Diagram 2.
RECRUITMENT
The principal investigator generated the random allocation sequence, allocated participants to each group and only he had access to information that could identify individual participants during or after data collection. The trial staff that were involved in the participant recruitment and data collection did not have ...
PMC10343048
Experiment 1: D-amphetamine
PMC10343048
Participants
±
Twenty healthy participants (15 male) with a mean (±SD) age of 22.9 (±5.17) were recruited. They had a mean weight (± SD) of 74.9 (± 14.2) kg and 14.5 (±1.5) years of education. Substance use information was unavailable for one participant: 13 of the participants were regular consumers of caffeinated drinks; 8 of them ...
PMC10343048
Drug and design
D-amphetamine (0.45 mg/kg, PO, Aspen Pharmacare, Australia) was used, giving a mean dosage of 33.7 mg based on the mean weight of the participants of 74.9 kg. Similar sizes and numbers of capsules containing either placebo (glucose) or 0.45 mg/kg d-amphetamine were prepared using 1, 2.5, 5, and 10 mg d-amphetamine sulf...
PMC10343048
Experiment 2: Caffeine
PMC10343048
Participants
Twenty healthy participants (14 males) with the mean (±SD) age of 22.2 (± 4.1) were recruited. They had a mean weight (± SD) of 80.3 kg (± 20.0) and 14.6 (±1.5) years of education. All except three were a regular consumer of caffeine (have taken at least one cup of caffeine-containing drinks per day, with 1.6 (±1.1) me...
PMC10343048
Drug and design
For this experiment, 200 mg of caffeine was administered in the morning (PO, BID; caffeine 200mg, PROLAB nutrition LLC, Chatsworth, USA). Caffeine was administered in gelatin capsules (size 0). Powdered glucose (Placebo) was also separately placed in the same type of capsule. This dose of caffeine was selected based on...
PMC10343048
General procedures for both experiments
PMC10343048
Psychological scale
Five rating scales were conducted once each day to measure Psychosis-like experiences (PLE): Brief Psychiatric Rating Scale (BPRS) [
PMC10343048
Physiological measures
BLOOD
Physiological changes were measured to assess whether the drug was active or not during the WM tests. Blood pressure (BP), temporal vein temperature (Temp) and heart rate (HR) were measured in triplicate five times each day to follow the time course of the drug and placebo effects on Systolic BP (SBP), Diastolic BP (DB...
PMC10343048
Working memory
WM tests were conducted in a well-lit room. We used forward spatial span (for SWM) and digit span (for VWM), from the Wechsler Adult Intelligence III (WAIS-III) [The same scoring criteria (the total scored and the maximum obtained) were used for both digit span and spatial span tasks. The maximum obtained indicates the...
PMC10343048
Spatial Span
Spatial span is a visuospatial analogue of the digit span test. This test was conducted at 90 min of post-d-amphetamine administration (0.45 mg/kg) and at 60 min post-caffeine administration. For each trial, ten randomly arranged blue squares (Psychcorp Mark) were shown on the table. The task began with the simplest le...
PMC10343048
Digit Span
This test was carried out after the spatial test, at 210 min of post-d-amphetamine administration and at 120 minutes of post-caffeine administration. The digits were pronounced in 1 s intervals by the examiner. The participant was asked to repeat the digits in the same order (forward) right after the examiner (0 s dela...
PMC10343048
Statistical analysis
generalised
The statistical analysis was performed using R programming version 3.5.3 (R Core Development Team 2018) and dply, ez, lme4, plyr, Rmisc, stats, sm packages. Normal Q-Q plots were used to check the residuals of the data. A repeated measure analysis (ANOVA) was used to analyse the data if the residuals indicated a suffic...
PMC10343048
Power analysis
We used G*Power 3.1 power calculator, and based our predicted mean difference (Drug-Placebo) and standard deviation of the difference on findings in our lab on the effect of DEX on the "embodiment" component of the RHI (paired samples t-test) indicating an effect size of 0.43 with alpha = 0.05, with a power of 0.80 (80...
PMC10343048
Results
PMC10343048
Experiment 1: D-amphetamine
PMC10343048
D-amphetamine effects on physiology
There were significant effects of d-amphetamine on heart rate (F[1, 19] = 49.8, p < 0.001, ƞ
PMC10343048
D-amphetamine effects on VWM and SWM
ANOVA with delay and drug as within-subject factors and drug order as a between-subjects factor indicated that there were no drug by delay interactions on VWM (maximum obtained F[3, 57] = 0.5, p = 0.67, ƞAs shown in
PMC10343048
The effect of d-amphetamine (0.45 mg/kg, PO) and placebo on working memory (WM) for maximum obtained and total scored.
Data are presented as maximum scored (A and C) or total scored (B and D) vs. delay conditions. A) The effect of d-amphetamine on spatial WM (maximum scored), relative to placebo; B) The effect of d-amphetamine on spatial WM (total scored), relative to placebo; C) The effect of d-amphetamine on verbal WM (maximum scored...
PMC10343048
D-amphetamine effect on PLE
As shown in
PMC10343048
Box plot of the effect of d-amphetamine (0.45 mg/kg, PO) and caffeine on Psychosis-like experiences (PLE).
D-amphetamine but not caffeine significantly increased PLE scores, relative to placebo (p < 0.001). C: Caffeine, D: D-amphetamine, P: Placebo.
PMC10343048
Effects of d-amphetamine and caffeine on each Psychological scale.
** significant at p < 0.01* significant at p < 0.05. Data are presented as Mean±SD.
PMC10343048
PLE and working memory
Pearson’s correlation was used to assess how changes in PLE scores (d-amphetamine–placebo) relate to WM change scores (d-amphetamine–placebo). There was a significant negative correlation between d-amphetamine induced changes in PLE and changes in WM (maximum obtained) at the 8 s delay (r = -0.47, p = 0.03, n = 20), bu...
PMC10343048
Experiment 2: Caffeine
PMC10343048
Caffeine effect on physiology
Analysis of variance with time and drug as within-subject factors and drug order as a between-subjects factor showed significant main effects of caffeine on systolic blood pressure (F[1, 19] = 27.9, p = 0.00004, ƞ
PMC10343048
Caffeine effect on PLE
Launay-Slade
Wilcoxon signed rank tests with continuity correction revealed that there were no significant effects of caffeine on any of the PLE scales: BPRS (V = 87, p = 0.63), MIS (V = 70.5, p = 0.91), and PAS (V = 96, p = 0.35), Launay-Slade (V = 5.5, p = 0.17) and SAPS (V = 91, p = 0.82).
PMC10343048
Caffeine effect on VWM and SWM
ANOVA with delay and drug as within-subjects factors and drug order as a between-subjects factor did not indicate significant drug by delay interactions for SWM (maximum obtained F[3, 57] = 0.48, p = 0.69, ƞThe effect of caffeine (200 mg, BID, PO) on SWM (a and b) and VWM (c and d) during forward tasks. Maximum obtaine...
PMC10343048
PLE and working memory
Although caffeine did not significantly influence PLE or WM, to compare the effects of caffeine and dexamphetamine we conducted the same correlation analysis. Changes in PLE scores (caffeine–placebo) were correlated with WM (maximum obtained) change scores (caffeine–placebo). There were no significant correlations betw...
PMC10343048
Discussion
The aim of the present two randomized studies was to investigate the effect of d-amphetamine (0.45 mg/kg, PO) and caffeine (200 mg, PO) on SWM and VWM performance in healthy subjects following delays in recall. The results showed that there are no main effects of d-amphetamine on the SST or the DST, relative to placebo...
PMC10343048
The effect of D-amphetamine and caffeine on WM
As there are no one generally accepted model to measure WM [In the present study, we used DST and SST to measure VWM and SWM, respectively. The DST is a simple span tasks used to measure auditory WM. SST is comparatively more complex tasks [We failed to find a main effect of d-amphetamine on SWM, which is in agreement ...
PMC10343048
PLEs in response to d-amphetamine and caffeine
The present study showed that d-amphetamine (0.45 mg/kg, PO), but not caffeine (200 mg), increased PLE scores. Previous reports showed that the level of dopamine released after dexamphetamine administration correlates with PLE scores [In the present study, caffeine did not significantly affect PLE measures. However, we...
PMC10343048
Strength and limitations of the study
The main strength of the present study was its study design (placebo controlled, within subject studies). It investigated the potential effects of d-amphetamine and caffeine on SWM and VWM performance using SST and DST at different delay conditions. This study used d-amphetamine at a moderate-high dose (~33 mg), about ...
PMC10343048
Conclusions
A moderate dose of d-amphetamine increased PLE on different scales. However, d-amphetamine does not directly affect performances on SST, but may impair SWM through its effects on PLEs that manifest during longer WM delays. In addition, moderate doses of caffeine do not affect performance on SST and DST. Overall, the pr...
PMC10343048
Supporting information
PMC10343048
Consort 2010 checklist for dexamphetamine and caffeine studies.
(DOC)Click here for additional data file.
PMC10343048
Dexamphetamine study participant information form.
(PDF)Click here for additional data file.
PMC10343048
Caffeine study participant information form.
(PDF)Click here for additional data file.
PMC10343048
Caffeine approval letter.
(PDF)Click here for additional data file.
PMC10343048
Dexamphetamine and caffeine studies test description.
(PDF)Click here for additional data file.
PMC10343048
Dexamphetamine study protocol.
(PDF)Click here for additional data file.
PMC10343048
Dexamphetamine working memory data.
(PDF)Click here for additional data file.
PMC10343048
Caffeine working memory data.
(CSV)Click here for additional data file.
PMC10343048
Caffeine study protocol.
(CSV)Click here for additional data file.The University of Western Australia (UWA-HDR) provided a PhD scholarship for FMK. We would like to thank each volunteer who participated in this study, and all colleagues who assisted in the data collection phase.
PMC10343048
Abbreviations
BLOOD
Diastolic Blood Pressuredorsolateral prefrontal cortexprefrontal cortexSpatial Working MemorySystolic Blood PressureVerbal Working MemoryWorking Memory
PMC10343048
References
PMC10343048
Abstract
PMC10013940
Background
ESSENTIAL TREMOR
Propranolol, a nonselective beta‐adrenergic blocker, has long been used as one of the standard treatments for essential tremor (ET). Repetitive transcranial magnetic stimulation (rTMS) has also been used for a long time as a substitution therapy for ET patients.
PMC10013940
Objective
The main aim of this study was to evaluate the antitremor effect of 1‐Hz (low‐frequency) cerebellar rTMS and compare it to the use of propranolol in ET patients.
PMC10013940
Methods
In this single‐blinded, randomized, controlled pilot study, a total of 38 patients with ET were randomized into two groups. One group (
PMC10013940
Results
tremor, disability
Low‐frequency rTMS of the cerebellum significantly improved tremor severity, specific motor tasks (writing, spiral drawing, and pouring), and FTM total scores on days 10 and 30. Nevertheless, we found no significant difference in functional disability at any point in time (
PMC10013940
Conclusion
cerebellar low‐frequency
We conclude that both cerebellar low‐frequency rTMS and propranolol could be effective treatment options for patients with ET, but it is not clear which method is more effective.This paper is the first study to compare the effects of rTMS and medication for ET patients. This will help healthcare providers and ET patien...
PMC10013940
INTRODUCTION
tremor, head tremor, movement disorders
ESSENTIAL TREMOR, MOVEMENT DISORDERS
Essential tremor (ET) is one of the most frequent movement disorders and is defined as 4–12 Hz kinetic or postural tremor mainly involving the bilateral upper region with or without head tremor or tremor in other locations (Bhatia et al., Existing studies indicate that propranolol and primidone remain the preferred ora...
PMC10013940
METHODS
PMC10013940
Participants
MOVEMENT DISORDER
Thirty‐eight patients with ET participated in the study. They were all recruited from the Department of Neurology in the General Hospital of Ningxia Medical University (Yinchuan, Ningxia, China). These patients were diagnosed based on Movement Disorder Society (MDS) criteria (Bhatia et al., All participants signed writ...
PMC10013940
Procedures
tremor
Subjects were randomized into two groups; one group (The Fahn–Tolosa–Marin (FTM) clinical scale, which consists of three subscales, was used to evaluate clinical effects. Part A evaluates tremor location/severity (amplitude), Part B assesses specific motor tasks (writing, spiral drawing, and pouring using dominant and ...
PMC10013940
rTMS cerebellar stimulation
CONTRACTIONS
In the rTMS group, patients received 600 pulses of rTMS in each cerebellar hemisphere at a frequency of 1 Hz and an intensity of 90% of the resting motor threshold (RMT) for 10 consecutive days. There were 20 trains for each 1‐Hz rTMS, and each train was performed for 30 s and followed by a 5‐s break, and each treatmen...
PMC10013940
Statistical analysis
±, SD
All statistics were performed using IMB SPSS for Windows, Version 21.0 (Armonk, NY), and all graphs were generated using GraphPad Prism 8.0. Continuous variables were expressed as the mean ± SD or median (25th percentile, 75th percentile), whereas categorical variables were expressed as percentages (%). Continuous vari...
PMC10013940
RESULTS
bradycardia, syncope, seizure, dizziness, headache, hypotension
ADVERSE EFFECTS
All 38 patients received their intended treatments. Twenty patients received rTMS of the bilateral cerebellum for 10 days, and all subjects tolerated rTMS sessions well without severe adverse effects (i.e., dizziness, headache, seizure, syncope). Eighteen patients received medical treatment with oral propranolol for 30...
PMC10013940
General clinical data
tremor
Of the 38 patients, 19 (50.0%) were female. Twenty‐two subjects (57.9%) had a positive family (first‐ or second‐degree relatives) history of ET. The mean age of the patients was 55.50 ± 13.55 years, and the mean duration of the tremor was 10.08 ± 8.30 years. All patients presented with hand tremor. Other locations of t...
PMC10013940
rTMS group
±, tremor
For the rTMS group, there was no significant effect in any clinical aspects of tremor: FTM score Part A, tremor severity (Fahn–Tolosa–Marin (FTM) clinical scale of ET patients before and after cerebellar rTMS (mean ± SD)Abbreviation: rTMS, repetitive transcranial magnetic stimulation.
PMC10013940
Propranolol group
±, tremor, SD
No aspect of tremor improved significantly at day 5 and day 10 after application of propranolol, and there were no obvious differences for FTM subscales and total score, including tremor severity (day 5 [Fahn–Tolosa–Marin (FTM) clinical scale of ET patients before and after oral propranolol (mean ± SD)
PMC10013940
Comparisons between two groups
tremor
Comparisons between the two groups indicated that for the FTM total score, the treatment difference (rTMS effect‐propranolol effect) was not significant on day 5 (Comparison of Fahn–Tolosa–Marin clinical scale between repetitive transcranial magnetic stimulation group and propranolol group on baseline, day 5, day 10, a...
PMC10013940
DISCUSSION
tremor, functional disability, dysfunction of the cerebellum
PATHOGENESIS, MOVEMENT DISORDERS
ET is one of the most common movement disorders, and multiple treatments are available (Sharma & Pandey, In our study, we found that when patients took propranolol orally at a dose of 30 or 60 mg for the first 10 days, there was no significant change in any of the FTM subscores or the total score. We observed that ther...
PMC10013940
CONCLUSION
tremor
Our findings suggest that 1‐Hz cerebellar rTMS is a relatively safe and potentially effective noninvasive treatment technique for ET patients that can reduce the amplitude of tremor and improve the patient's specific motor tasks. Meanwhile, because of its advantages of convenience, effectiveness, and relatively cheap p...
PMC10013940
AUTHOR CONTRIBUTIONS
Mengran
The work described here was done in mutual assistance with all the authors. Haining Li contributed to the research design and reviewed and edited the manuscript. Jiang Cheng collected references and revised the manuscript. Yue Lv completed the data collection, performed statistical analysis, and drafted the manuscript....
PMC10013940
CONFLICT OF INTEREST STATEMENT
The authors declare no conflicts of interest.
PMC10013940
PEER REVIEW
The peer review history for this article is available at
PMC10013940
DATA AVAILABILITY STATEMENT
The datasets used and analyzed in the current study are available from the corresponding author on reasonable request.
PMC10013940
REFERENCES
PMC10013940
Background
neuromuscular block, residual neuromuscular blockade
Neostigmine used to reverse the muscle relaxants should be guided by neuromuscular monitoring, as the degree of spontaneous pre-reversal recovery is the key to success to reverse the neuromuscular block. But neuromuscular monitoring is not always available for some patients during anesthesia and, in consequence, we nee...
PMC9824919
Methods
hypoxia, hernia, muscle paralysis
ADVERSE EVENTS, HYPOXIA
A parallel, randomized, controlled noninferiority study was conducted. We enrolled aged 3 months to 12 years old patients who underwent inguinal hernia repair under general anesthesia. The enrolled patients were randomly divided into experimental and control groups. After surgery, children in the experimental group wer...
PMC9824919
Results
A total of 120 children were included in this study, with 60 in the experimental group and 60 in the control group. There was no significant difference in the incidence of rNMB after extubation between the groups (45/60 vs 44/60, RR 1.02 [95% CI, 0.83 to 1.26],
PMC9824919