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Author contributions
P.H.
P.H., Y.H. and C.Z., conceptualized the research question, designed the study. Y.D., Y.C., P.J. and J.C. performed the statistical data analysis, and wrote the article. Y.C., J.Z., and Y.Z. interpreted the results. S.E., Y.Z., and Z.L. revised the article for important intellectual content. All authors reviewed the man...
PMC10439129
Funding
No competing financial interests exist. The authors had financial support for the submitted work as specified in the funding section, but the funding institutions did not have any role in the writing of the article or the decision to submit it for publication; no financial relationships with any organizations that migh...
PMC10439129
Data availability
The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.
PMC10439129
Competing interests
The authors declare no competing interests.
PMC10439129
References
PMC10439129
Key Contribution
temporomandibular disorders, headaches, TMDs, masticatory muscle pains, masticatory muscle pain, orofacial pain, headache, myogenous TMD, tenderness, capitis, OVAS
TEMPOROMANDIBULAR DISORDERS, DISORDERS
These authors contributed equally to this work.This study aimed to evaluate the efficacy of botulinum toxin type A (BoNT/A) in patients with temporomandibular disorders (TMDs) associated with masticatory muscle pain (MMP) and headaches. This randomized, double-blind, placebo-controlled pilot study is the first clinical...
PMC10610636
1. Introduction
myofascial pain, masticatory myalgia, TMD, traumatic injuries, TMDs, dystonia, masticatory muscle disorders, strabismus, pain, musculoskeletal disorders, parafunction, muscle hyperfunction, hyperhidrosis, blepharospasm
MYOFASCIAL PAIN, TMJ, DYSTONIA, STRABISMUS, MUSCULOSKELETAL DISORDERS, HEMIFACIAL SPASM, TEMPOROMANDIBULAR DISORDERS, BLEPHAROSPASM
Temporomandibular disorders (TMDs) refer to a range of conditions affecting the masticatory muscles or the temporomandibular joint (TMJ) and are the second most common musculoskeletal disorders causing pain and functional impairment [TMDs are considered to have a multifactorial etiology, commonly associated with muscle...
PMC10610636
2. Results
PMC10610636
2.1. Participants
A total of 21 patients (19 women and 2 men; age range of 21–53 years) clinically diagnosed with MMP were included in the study. They were randomly divided into two groups and received BoNT/A or saline injections. There were no significant differences in sex and age between the groups; thus, the homogeneity of the gener...
PMC10610636
2.2. Differences between Groups
PMC10610636
2.2.1. Comparison of Changes over Time within Groups
According to the Friedman test, which was used to verify whether the change over time was significant in the two groups, no significant difference in OVAS, TPs, MMO, HVAS, or HF was observed in the control group, whereas in the experimental group, except for MMO, OVAS (
PMC10610636
2.2.2. Comparison of Changes between Groups
A Mann–Whitney U test was conducted to verify whether there was a significant difference between the groups in the amount of change after 4, 8, and 12 weeks of pre-injection. Consequently, the changes in OVAS, MMO, HVAS, and HF did not show significant differences between the experimental and control groups at all time...
PMC10610636
3. Discussion
TMD, Headache, migraine headaches, headaches, pain, orofacial pain, head and neck pain, headache, migraine
TENSION-TYPE HEADACHES, MIGRAINE HEADACHES, MIGRAINE
Instead of conservative treatments, such as physical therapy, the use of non-steroidal analgesic agents, and the local injection of anesthetics and steroids, BoNT/A is being increasingly used as an adjuvant treatment for head and neck pain, such as tension-type headaches and migraine headaches [In this study, OVAS and ...
PMC10610636
4. Conclusions
TMD, headache
According to our study results, after BoNT/A injection, significant values were observed in the experimental group over time, and TPs decreased. Therefore, BoNT/A injection can be suggested as a relatively effective treatment for patients with TMD presenting with MMP and headache compared to saline placebo.
PMC10610636
5. Materials and Methods
PMC10610636
5.1. Subjects
joint-related disease, TMD, Orofacial Pain, TMDs, pain, headache, capitis, arthralgia
AMYOTROPHIC LATERAL SCLEROSIS, FIBROMYALGIA, MOTOR NEUROPATHY, MYASTHENIA GRAVIS, LAMBERT SYNDROME, DISEASES
The clinical trial included 21 patients (2 men and 19 women; age range of 21–53 years) with chief complaints of MMP with TMDs and headache who were enrolled at the Department of Orofacial Pain and Medicine, Dental University of Yonsei, Seoul, Republic of Korea. At their first visit, patients were screened to determine ...
PMC10610636
5.2. Study Design
orofacial pain, TMD, headache pain, headaches
This was a prospective, randomized, double-blind, placebo-controlled clinical trial. Clinicians checked the demographic information, medical history, and medication history of participants. Participants completed questionnaires regarding TMD and headache pain for measurement and assessment of clinical values. The inten...
PMC10610636
Author Contributions
Conceptualization, A.H.K. and S.T.K.; methodology, A.H.K. and S.T.K.; formal analysis, S.R.K.; investigation, M.C. and S.T.K.; data curation, S.R.K. and M.C.; writing—original draft preparation, S.R.K.; writing—review and editing, S.R.K. and S.T.K.; supervision, S.T.K. All authors have read and agreed to the published ...
PMC10610636
Institutional Review Board Statement
The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of the Yonsei University Dental Hospital (Approval No. 2-2019-0061, date of approval; 14 November 2019).
PMC10610636
Informed Consent Statement
Informed consent was obtained from all subjects involved in the study.
PMC10610636
Data Availability Statement
The data presented in this study are available in this article.
PMC10610636
Conflicts of Interest
The authors declare no conflict of interest.
PMC10610636
References
orofacial pain, headache
(Homogeneity of general characteristics between the experimental and control groups.Exp, experimental group; Con, control group.Differences in variables in the experimental and control groups according to time.Exp, experimental group; Con, control group; OVAS, the intensity of orofacial pain; TPs, the number of tender ...
PMC10610636
Subject terms
disability, pain
ADVERSE EVENTS, RECRUITMENT, CORTEX, CHRONIC LOW BACK PAIN
Chronic low back pain (CLBP) is a disabling condition worldwide. In CLBP, neuroimaging studies demonstrate abnormal activities in cortical areas responsible for pain modulation, emotional, and sensory components of pain experience [i.e., pregenual and dorsal anterior cingulate cortex (pgACC, dACC), and somatosensory co...
PMC9860016
Introduction
pain
CHRONIC LOW BACK PAIN
Chronic low back pain (CLBP) is a significant and disabling health condition affecting individuals, the wider community, and the healthcare systemResting-state cortical activity alterations have been demonstrated in individuals with CLBPElectroencephalography (EEG) based Neurofeedback (NF) is a brain-computer interface...
PMC9860016
Methods
PMC9860016
Trial registration and ethical approval
Prospectively registered in Australian and New Zealand Clinical Trials Registry (
PMC9860016
Study design
SECONDARY, CORTEX
Double-blind, randomized, placebo-controlled feasibility study with four parallel intervention arms (Fig. Study design and timelines. ISF-NF: infraslow frequency neurofeedback, pgACC: pregenual anterior cingulate cortex, dACC: dorsal anterior cingulate cortex, SSC: primary somatosensory cortex. Study assessment session...
PMC9860016
Randomization
pain
A research administrator, not involved in treatment/assessment, randomized, and assigned participants using a computerized open-access randomization software program without applying any restrictions (on a 1:1:1:1 basis) to either:Group-1: ISF-NF up-training pgACC, i.e., modulate the descending pain inhibitory pathwayG...
PMC9860016
Blinding
Participants and outcome assessor were blinded. The success of blinding was assessed after completion of intervention using the question, “What type of treatment do you believe that you/the participant received respectively?” The confidence in their judgement was assessed on an 11-point NRS
PMC9860016
Participants and eligibility criteria
All participants were voluntarily recruited from the community through advertisement flyers. All participants provided written informed consent prior to study enrolment. Participants were screened for eligibility and enrolled by a musculoskeletal physiotherapy researcher.
PMC9860016
Inclusion and exclusion criteria
Morris Disability, disability, pain
CENTRAL SENSITIZATION
Ages of 18 to 75 years, pain in the lower back region for ≥ 3 months, a score of ≥ 4 on an 11-point NPRS in 4 weeks prior to enrolment, a disability score of ≥ 5 on Roland–Morris Disability Questionnaire (RMDQ)At baseline assessment, all participants completed questionnaires to capture demographics, and clinical charac...
PMC9860016
Sample size
As this was a pilot study to determine the feasibility of a future fully powered RCT, sample size calculation was not performed. Based on statistical advice, a sample of 60 participants (15/group) was considered enough to determine feasibility issues and obtain treatment estimates for designing the full trial.
PMC9860016
Intervention
Source localised EEG ISF-NF was administered three times a week (30 min/session) for four consecutive weeks (12 sessions) by the researcher (physiotherapy background) experienced in delivering neuromodulation techniques. Treatment was delivered using a 21-channel DC coupled amplifier and BrainAvatar™ sLORETA software v...
PMC9860016
ISF-NF treatment groups
chronic pain, pain
CHRONIC PAIN
It has been demonstrated that chronic pain can be considered as an imbalance between pain input and pain suppression. Our protocols are derived from this theory utilizing source localization neurofeedback targeting the ratio between pgACC, SSC, and dACC. For the current study, we developed EEG-NF training programs to u...
PMC9860016
Placebo-NF group
To create identical auditory feedback to ISF-NF groups, participants in placebo-NF group listened to a random set of pre-recorded sound files (n = 12), sourced from a database of recorded audio files (using audacity software) of healthy participants that underwent EEG source localised ISF-NF training (targeting ratio b...
PMC9860016
Outcome measures
PMC9860016
Feasibility measures
RECRUITMENT
Included recruitment rate (number of participants recruited per month), proportion of participants recruited from total number screened (expressed as a percentage), adherence to intervention (measured as number of treatment sessions attended by each participant expressed as a percentage of the total number of sessions)...
PMC9860016
Clinical measures
Pain
Brief Pain Inventory (BPI)
PMC9860016
Electroencephalogram
Resting-state eyes-closed EEG (~ 10 min) was obtained using SynAmps-RT Amplifier (Compumedics-Neuroscan). Sixty-four electrodes were placed in 10–10 International placement and impedances were checked to remain below 5kΩ. Data were resampled (128 Hz), band-pass filtered (0.005–0.2 Hz), plotted in EEGLAB and ICoN softwa...
PMC9860016
Data analysis
primary pain, pain
Data were analysed using SPSS_v27.0. As this was a feasibility study, tests for significance to compare clinical and EEG measures between study groups were not performed, but descriptive statistics were applied. Feasibility outcomes are reported based on recommendations.Clinical outcomes were analyzed based on intentio...
PMC9860016
Protocol changes
Following changes were made to the registered protocol based on the ethical review and the peer reviewer comments.
PMC9860016
Results
PMC9860016
Participants
CORTEX
Sixty participants were enrolled and randomised equally into four treatment groups (Fig. Flow of participants through the study phases. pgACC: pregenual anterior cingulate cortex, dACC: dorsal anterior cingulate cortex, SSC: primary somatosensory cortex, ITT: intention to treat.Demographics and clinical characteristics...
PMC9860016
Feasibility
PMC9860016
Recruitment
MAY, RECRUITMENT
The total recruitment period was 9 months (July 2020 to March 2021), with the last follow up completed in May 2021. This feasibility trial was stopped in May 2021 as the desired sample size was reached (n = 60) and all follow ups completed. Our average recruitment rate was seven participants per month. The proportion o...
PMC9860016
Dropouts
Of the total participants enrolled (n = 60), we lost 8 participants following baseline assessment session (Fig. 
PMC9860016
Treatment adherence and engagement
NRS
The average treatment adherence rate for all groups was 80%. The individual treatment adherence scores were 88%, 73%, 76%, and 81% for pgACC, dACC + SSC, Ratio, and Placebo groups respectively.The NRS scores for mood, motivation, and treatment engagement were comparable between treatment groups. The Median (95% CI) for...
PMC9860016
Integrity of blinding
Participant blinding was deemed successful as the treatment group was not revealed to them in any way. In total, 51% of participants incorrectly predicted the treatment group or responded, “don’t know”. The remaining 49% of participants, although correctly predicted their treatment groups, based their decision primaril...
PMC9860016
Adverse effects
ADVERSE EFFECTS, ADVERSE EFFECTS, CORTEX
No serious adverse effects were reported. Several transient low intensity (< 3 on NRS) negative side effects, rated to be related to ISF-NF treatment, were reported by a few participants (Fig. Adverse effects reported by participants during the neurofeedback treatment sessions. pgACC: pregenual anterior cingulate corte...
PMC9860016
Acceptability and satisfaction
SD
All participants, irrespective of treatment group, reported moderate to high levels of acceptability with Mean ± SD of 7.8 ± 2.0 (pgACC), 7.5 ± 2.7 (dACC + SCC), 8.2 ± 1.9 (Ratio), and 7.7 ± 1.5 (Placebo), respectively. Further, moderate to high levels of satisfaction were also reported with Mean ± SD of 5.7 ± 2.9 (pgA...
PMC9860016
Pain
pain
All treatment groups demonstrated a favourable change in pain measures at all timepoints (Table
PMC9860016
Function
disability
The RMDQ scores demonstrated a trend of reduction in disability in all treatment groups (Table
PMC9860016
Global perceived effect
At 1-month follow-up, the proportion of participants who perceived meaningful (≥ + 2) global effect was higher in pgACC (67%) and dACC + SSC (64%) group, when compared to ratio (46%) and sham (46%) group.
PMC9860016
QST
Due to high variability in measures, no differences in trends were observed in any of QST variables at 1-month follow-up (Table
PMC9860016
EEG measures
CORTEX
Descriptive data for CD and FC measures at all time points are presented in Supplementary Tables Heatmaps for mean percentage change to baseline in functional connectivity in the infraslow frequency bands. pgACC: pregenual anterior cingulate cortex, dACC: dorsal anterior cingulate cortex, SSC: primary somatosensory cor...
PMC9860016
Discussion
chronic pain, disability, pain
CHRONIC PAIN, SECONDARY, RECRUITMENT
Re-training cortical activity through real-time EEG-based source localised ISF-NF is a novel approach for treatment of chronic painOur results demonstrate that a fully powered trial to test efficacy of EEG-based ISF-NF training for treatment of CLBP is feasible. A sizable number of individuals with CLBP were interested...
PMC9860016
Limitations
LBP, disability, pain
The primary limitations of this pilot feasibility study were small sample size and descriptive comparisons to infer trends in clinical and EEG outcomes. However, these limitations reflect the purpose of our feasibility study, which was to provide estimates of clinical outcome measures (pain and disability) to support s...
PMC9860016
Conclusions
disability, pain
The ISF-NF training is feasible, safe, and an acceptable treatment approach for CLBP. A positive trend of the effect of ISF-NF treatment was observed on pain and disability outcomes in all groups. In particular, the pgACC uptraining group experienced favourable outcomes and perceived the intervention to be highly effec...
PMC9860016
Supplementary Information
The online version contains supplementary material available at 10.1038/s41598-023-28344-2.
PMC9860016
Author contributions
Conceptualization: D.B.A., D.D.R., R.M., and S.V.; Methodology: D.B.A., D.D.R., R.M., and S.V.; N.F. protocol programming: M.S.; Data curation: JM, FO, D.B.A.; Writing—original draft preparation: D.B.A., D.D.R., and R.M.; writing—review and editing: D.B.A., D.D.R., R.M., S.V., M.S., J.M., and F.O. All authors have crit...
PMC9860016
Funding
BRAIN
This work was funded by the Otago Medical School Trust (Dean’s Bequest) Funding and Brain Health Research Centre (through a Philanthropist). The funding sources were not involved in the study design; the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the ar...
PMC9860016
Data availability
Datasets generated during and/or analysed during the current study are available from the corresponding author upon reasonable request.
PMC9860016
Competing interests
DDR
MS is the owner of Neurofeedback Therapy Services of New York. He helped with the programming of the neurofeedback protocols tested in the current study. The cortical areas to be targeted, its co-ordinates and the desired training protocol (uptraining/downtraining) were provided by the principal investigators (DDR and ...
PMC9860016
References
PMC9860016
1. Introduction
Obesity, T2D, cardiovascular disease
OBESITY, TYPE 2 DIABETES, CARDIOVASCULAR DISEASE
Liver-expressed antimicrobial peptide-2 (LEAP-2) is associated with caloric intake and glucose metabolism. Obesity raises type 2 diabetes (T2D) and cardiovascular disease risk [LEAP-2 is expressed from the small intestine and liver [
PMC9918887
2. Methods
obesity, Appetite
OBESITY, BLOOD, TOLERANCE
Participants: Twenty-five females were randomized into LCD (Cardiorespiratory Fitness: A cycle ergometer with indirect calorimetry (Carefusion, Vmax CART, Yorba Linda, CA, USA) was used to determine the cardiorespiratory fitness (VOAnthropometrics: Participants were instructed to fast for approximately 4 h prior to bod...
PMC9918887
3. Results
±
BLOOD
Participant Characteristics: LCD and LCD+INT reduced caloric intake over the intervention by design, and there was no difference between groups (−752.1 ± 230.4 vs. −422.7 ± 203.3 kcals/day; Blood Lipids and Glucose Metabolism: LCD and LCD+INT reduced cholesterol (Circulating LEAP-2: Both LCD and LCD+INT decreased fasti...
PMC9918887
4. Discussion
obesity, T2D, fat loss, hypoglycemia, caloric deficit
OBESITY, HYPOGLYCEMIA, CVD
The main observation of this work is, short-term caloric restriction with or without exercise decreased fasting LEAP-2 in women with obesity. However, when examining the impact of glucose ingestion on LEAP-2, it was observed that LCD raised LEAP-2 more than LCD+INT. The observed reductions in fasting LEAP-2 and rise in...
PMC9918887
Author Contributions
Conceptualization and work design by S.K.M. Data collection and/or analysis by S.K.M. and T.J.R. Statistical analysis by T.J.R. and S.K.M. All authors have read and agreed to the published version of the manuscript.
PMC9918887
Institutional Review Board Statement
The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the University of Virginia Ethics Committee (IRB-HSR #18316).
PMC9918887
Informed Consent Statement
All participants gave their informed consent before they participated in the study.
PMC9918887
Data Availability Statement
These data have not been made publicly available. However, the corresponding author (S.K.M.) can provide further information on the data upon reasonable request.
PMC9918887
Conflicts of Interest
The authors declare no conflict of interest.
PMC9918887
References
INSULIN RESISTANCE
Circulating LEAP-2 before and after treatments. Note: Raw data shown as mean ± SEM, log transformed for analysis. (Correlations of LEAP-2 to Appetite, Acyl-Ghrelin, and Free Fatty Acids. Note: LOG indicates variables transformed for analysis, (Body composition, Fitness, and Dietary Intake.Note: Data expressed as mean ±...
PMC9918887
1. Introduction
overweight or obesity, T2DM, prediabetes, diabetes
PREDIABETES, EVENTS, TYPE 2 DIABETES MELLITUS, INSULIN SENSITIVITY, DIABETES
These two authors contributed equally to this work.The global prevalence of type 2 diabetes mellitus (T2DM) has surged in recent decades, and the identification of differential glycemic responders can aid tailored treatment for the prevention of prediabetes and T2DM. A mixed meal tolerance test (MMTT) based on regular ...
PMC10609681
2. Materials and Methods
PMC10609681
2.1. Clinical Trial and Dietary Intervention
T2D, T2DM
TYPE 2 DIABETES, INSULIN SENSITIVITY
Data from the MEDGI-Carb trial were used in the present study because participants were at risk of developing T2DM, and the intervention tested the effect of a high vs. low GI diet within the context of a healthy eating pattern, i.e., a Mediterranean diet. By including individuals with elevated risk of T2D and using da...
PMC10609681
2.2. Mixed Meal Tolerance Tests
BLOOD
Breakfast and lunch MMTT were performed at baseline, mid-testing (USA only), and post-intervention. Prior to all testing days, participants were instructed not to eat or drink anything (except a small amount of water) from 10:00 p.m., the evening before the visit. Fasting blood samples were collected at the time point ...
PMC10609681
2.3. Oral Glucose Tolerance Test
BLOOD
Participants completed OGTT at baseline, mid-testing (USA only), and post-intervention. Fasting blood samples were collected at TP −15 after 15 min of rest and at TP −5. At TP 0, participants were instructed to consume a test beverage containing 75 g glucose dissolved in water within 5 min. No additional fluids were pe...
PMC10609681
2.4. Fecal Microbiota
LYSIS
During pre- and post-intervention study days, participants were asked to collect fecal samples using a stool sampling collection kit. Samples were taken using an EasySampler Stool Collector and a sample tube with a spoon lid. The sample was protected by being placed in yet another tube and stored immediately in the fre...
PMC10609681
2.5. Mechanistic Model of Glucose Regulation
A modified version of the minimal glucose model [The dynamics of the model are described using compartments that represent mechanisms in the glucose–insulin system, and the exchange rates between compartments are described using rate constants. The model assumes that the ingested glucose is delayed by the digestive sys...
PMC10609681
2.6. Statistical Analyses
The parameters of the model were estimated within the nonlinear mixed effects model framework [The individual parameters The association between response clusters and gut microbiota was investigated using ANOVA on selected genera (explained in the fecal microbiota section) that were reported to associate with glycemic ...
PMC10609681
3. Results
In total, 155 individuals completed the two MMTTs and OGTTs (baseline and wk. 12) and were included in the analyses. Calculations on fecal microbiota were based on 130 individuals who provided two fecal samples within the participants that performed the two MMTT and OGTTs (baseline and wk. 12) (
PMC10609681
Postprandial MMTT Glucose Responses
diabetic, prediabetes
PREDIABETES
Individual parameters of the kinetic model (baseline, amplitude, damping, and frequency) from Equation (1) were estimated using the postprandial MMTT glucose response at baseline and wk. 12. The parameters were successfully estimated with RSE < 43% in all cases, which indicated certainty in the estimates. Variation amo...
PMC10609681
4. Discussion
T2D, T2DM, nausea
EVENTS, INSULIN SENSITIVITY
To dissect glucose data into features representing postprandial events, we used a model with only four parameters to identify clusters from standardized breakfast meal tolerance test responses that strongly related to T2DM risk factors. Although the model did not capture all systematic variation in the data, it was fle...
PMC10609681
5. Conclusions
T2D, T2DM
We used a simple model to successfully describe glucose response to a standardized breakfast MMTT based on common foods and identified two response clusters that were associated differently with T2DM risk markers and gut microbiota. Future studies should investigate if such clusters can be identified by an algorithmic ...
PMC10609681
Supplementary Materials
The following supporting information can be downloaded at Click here for additional data file.
PMC10609681
Author Contributions
Conceptualization, R.L. and V.S.; methodology, V.S. and M.W.; software, V.S.; validation, V.S.; formal analysis, V.S.; investigation, V.S. and T.H.; resources, R.L., G.R. and W.W.C.; data curation, R.L., G.R., R.E.B. and W.W.C.; microbiota analyses, J.D., E.A.P. and V.S.; writing—original draft preparation, T.H. and V....
PMC10609681
Institutional Review Board Statement
RECRUITMENT
The study was conducted in accordance with the Declaration of Helsinki and approved by The Regional Ethical Review Board, Gothenburg, Sweden (DNR 663-17, approved: 14 December 2017), the institutional review board of Federico II University (n. 175/17, approved: 25 October 2017), and the biomedical institutional review ...
PMC10609681
Informed Consent Statement
Written informed consent was obtained from all participants involved in the study and was obtained prior to any collection of data or sampling.
PMC10609681
Data Availability Statement
The data presented in this study are available upon reasonable request from the corresponding author.
PMC10609681
Conflicts of Interest
G.R. is a member of the Scientific Advisory Board of the Nutrition Foundation of Italy and the Istituto Nutrizionale Carapelli Foundation; he is a member of the Health and Wellbeing Advisory Board of the Barilla G&R. Fratelli Company and Consultant for a Metabolic Health Masterclass sponsored by Nestlè. R.B. is current...
PMC10609681
References
diabetic”, diabetic, diabetes
IMPAIRED GLUCOSE TOLERANCE, DIABETES
Example dynamics generated from the model in Equation (1). The blue curve is characterized by a fast biphasic response to the MMTT, thus having high frequency (Model fit to postprandial breakfast MMTT response at baseline of 16 randomly selected representative subjects. Here, points represent measurements, and lines re...
PMC10609681
Background
anxiety
Full list of collaborator names appear in Child anxiety before general anaesthesia and surgery is common. Midazolam is a commonly used premedication to address this. Melatonin is an alternative anxiolytic, however trials evaluating its efficacy in children have delivered conflicting results.
PMC10797512
Methods
This multicentre, double-blind randomised trial was performed in 20 UK NHS Trusts. A sample size of 624 was required to declare noninferiority of melatonin. Anxious children, awaiting day case elective surgery under general anaesthesia, were randomly assigned 1:1 to midazolam or melatonin premedication (0.5 mg kg
PMC10797512
Results
The trial was stopped prematurely (
PMC10797512
Conclusion
anxiety
Melatonin was less effective than midazolam at reducing preoperative anxiety in children, although the early termination of the trial increases the likelihood of bias.
PMC10797512
Clinical trial registration
ISRCTN registry: ISRCTN18296119.
PMC10797512
Keywords
Handling Editor: Rupert Pearse
PMC10797512