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2.3. Study Population
Children 1–14 years of age, enrolled at a study site, on or initiating ART, and with a consenting caregiver were enrolled to the study. Participant characteristics at enrollment have been previously published [
PMC10612029
2.4. Data Collection and Management
We abstracted routinely collected data from standardized Ministry of Health forms in medical files and registers using direct, electronic data entry via tablets into a REDCap database. Similarly, we entered study-collected data, including DRT results, in this REDCap database.
PMC10612029
2.5. Primary Analytic Outcome
A participant was considered to have clinically significant DR if they had any mutation listed for NRTI and NNRTI drugs with a penalty score or if listed as “major” for PIs by Stanford’s Genotypic Resistance Interpretation Algorithm (i.e., Stanford HIVdb) on any DRT [
PMC10612029
2.6. Exposures and Covariates
VF
We selected potential risk factors a priori, based on the existing literature and content knowledge, which included age, sex, duration on ART, prior ARV exposure, and prior history of VF [
PMC10612029
2.7. Statistical Analysis
HIV drug, death, viral suppression
REGRESSION
First, we describe the proportion of participants from either group who underwent DRT as part of the study intervention or at the study end, per protocol, and the proportion with DR mutations detected by HIV drug classes, e.g., NRTIs, NNRTIs, and PIs. All DRTs for each participant were reviewed, but only one DRT result...
PMC10612029
3. Results
VF
A total of 704 children were enrolled in the study with a median age 9 years (interquartile range (IQR) 7, 12); 344 (49%) were female, and the median time on ART was 5 years (IQR 3, 8). A total of 349 (49.5%) and 355 (50.5%) of the CHIV were randomized to the intervention and control groups, respectively. Overall, 382 ...
PMC10612029
3.1. Drug Resistance among Children on ART with Virologic Failure
viremia
MINOR, VIREMIA
Among the one hundred and six participants with at least one DRT result, all demonstrated at least one clinically significant mutation or minor DR mutation, as defined by the Stanford HIV Database. A total of 93 (87.7%) had clinically significant mutations, and 13 (12.3%) had minor mutations only (Among the eighty-eigh...
PMC10612029
3.2. Characteristics Associated with Major Drug Resistance
The associations between participant characteristics and clinically significant DRs are shown in
PMC10612029
3.3. Clinical Management and Outcomes of Children with DRT
VF
The CMC carried out case reviews for all participants with DRT results and recommended an ART regimen change for 46 (43%) out of the 106 participants with a DRT. In the control group, 22 participants had a DRT after the 12-month study visit, and 100% had any DR with 19 (86%) with major DR. Eight of those with results (...
PMC10612029
4. Discussion
virologic failure, VF
Our study identified major DR in most CHIV with VF. The last published comprehensive DR surveillance for children in Kenya was in 2013 before the changes to the recommend PI-containing ART for children less than three years of age came into effect [Developing strategies to optimize cost-effective use for targeted DRT a...
PMC10612029
5. Conclusions
VF
The findings from this study demonstrated high levels of major DR in children living with VF. Providers and policy makers should consider the identified factors associated with major DR when considering which children may benefit most from DRT while it remains a limited resource. Further research is needed to understan...
PMC10612029
Author Contributions
S.A.H.
Conceptualization, L.A., R.C.P., P.O., I.M., K.K.T. and G.J.-S.; methodology, L.A., R.C.P., P.O., B.H.C. and K.K.T.; formal analysis, G.W., K.K.T., L.A. and R.C.P.; investigation, L.A., R.C.P., P.O., I.M., J.W., L.K., E.K. (Enericah Karauki) and K.K.T.; software: N.Y., K.K.T., B.O. and L.K.; resources, P.O., L.A., R.C....
PMC10612029
Institutional Review Board Statement
The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Boards of the African Medical and Research Foundation (AMREF) (Protocol P545, approved 27 November 2018) and Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH) (Protocol GEN/21A/V94, approved 19 S...
PMC10612029
Informed Consent Statement
Informed consent was obtained from legal guardians for all subjects involved in the study and assent for those 13 years of age and older.
PMC10612029
Data Availability Statement
DISEASE
The de-identified data presented in this study are available on request from the corresponding author. The data are not publicly available due to the sensitive nature of the disease being studied.
PMC10612029
Conflicts of Interest
The authors declare no conflict of interest.
PMC10612029
Subject terms
ESPB, pain
COMPLICATIONS
Various techniques have been formulated to reduce pain and ensure early recovery after surgery, as these are major concerns among surgeons, anesthesiologists, and patients. Erector spinae plane block (ESPB), the injection of local anesthetic into the fascial plane, is a simple and novel analgesia technique widely used ...
PMC10368743
Introduction
neuropathic, ESPB, pain
Surgeons, anesthesiologists, and patients have been most concerned about pain and early recovery after surgery. Various efforts have been introduced to help patients recover early after surgery, and the Enhanced Recovery After Surgery (ERAS) protocol is the most comprehensive strategy for these efforts. ERAS regimens h...
PMC10368743
Methods
PMC10368743
Study design and ethical consideration
This is a double-blind, prospective randomized controlled trial. The institutional review board of Seoul National University Bundang Hospital approved this study (No. B-1907-553-002). The study protocol was registered with the University Hospital Medical Information Network Clinical Trials Registry (
PMC10368743
Patients
coagulation abnormality, allergic reaction
ALLERGIC REACTION, COMPLICATIONS
The adult patients who were scheduled for elective LCS aged over 19 years and with an American Society of Anesthesiologists (ASA) physical status of class I or II were included in this study. Patients in whom needle insertion and bupivacaine injection could cause significant complications, including those with a histor...
PMC10368743
Randomization and blinding
An independent researcher prepared 64 identical opaque envelopes for randomization, each containing a random number from 1 to 64. Each number in the envelope was linked to the group allocation number generated by the randomization program (Research Randomizer,
PMC10368743
ESPB procedures
ESPB
THORACIC
In the operating room, an independent anesthesiologist responsible for the EBPB but not involved in the rest of the protocol performed the procedure. With a patient seated, a 5–12-MHz linear ultrasonic probe (Fujifilm Sonosite Inc., Bothell, WA, USA) was placed parasagittally lateral to the spinous process between Thor...
PMC10368743
General anesthesia
ESPB
MUSCLE RELAXATION, NEUROMUSCULAR BLOCKADE
After the ESPB procedure, the patient’s vital signs were monitored in the supine position using electrocardiography, non-invasive blood pressure measurement, pulse oximetry, and capnography. Then, general anesthesia induction was initiated with 1.2–1.5 mg/kg of propofol and 0.6 mg/kg of rocuronium after denitrogenation...
PMC10368743
Postoperative pain management
When the surgery was completed, an intravenous patient-controlled analgesia device (PCA; ANAPLUS
PMC10368743
Study outcomes
PONV, postoperative pain, postoperative nausea and vomiting
SECONDARY
The primary outcome variable was the total amount of fentanyl required in the first 24 postoperative hours. The secondary outcome variables were the time to first ambulation and length of hospitalization after surgery. The postoperative pain score at each time point, the number of rescue analgesic treatments, and the i...
PMC10368743
Statistical analysis
ESPB
The number of participants required for this trial was estimated using G*power version 3.1.9.6 (Heinrich Heine University, Düsseldorf, Germany). In the pilot study, the amount of fentanyl required during the first 24 postoperative hours in patients who received LCS was 685.5 ± 220.7 (mean ± standard deviation) µg. Assu...
PMC10368743
Discussion
long-term opioid dependency, postoperative pain, visceral pain, ESPB, nausea and vomiting, pain, chronic pain
CHRONIC PAIN, COMPLICATIONS
This study demonstrated that ultrasound-guided bilateral ESPB reduced fentanyl requirement and postoperative pain in the patients receiving LCS. Moreover, ESPB facilitated patient ambulation and reduced hospital stay. These results suggest that ESPB can improve the quality of postoperative recovery. This is the first r...
PMC10368743
Author contributions
J.-W.P., E.-K.K., and S.P. conceptualized and designed the study; J.-W.P. and S.P. collected the original data; E.-K.K. and J.L. analyzed the data; J.H.L. and F.S.N. interpreted the analysis and helped with quality control; J.-W.P., E.-K.K., S.P., and J.H.L. prepared the original draft; W.K.H. and F.S.N. reviewed and e...
PMC10368743
Data availability
The datasets supporting the findings of this study are available from the corresponding author upon reasonable request.
PMC10368743
Competing interests
The authors declare no competing interests.
PMC10368743
References
PMC10368743
Supplementary Information
ACUTE MYELOID LEUKEMIA, REMISSION, AML
We previously conducted a randomized phase II trial of OCV-501, a WT1 peptide presented by helper T cells, in elderly AML (acute myeloid leukemia) patients in first remission, indicating no difference in 2-year disease-free survival (DSF) between the OCV-501 and placebo groups. Here, we analyzed 5-year outcome and biom...
PMC10123586
Keywords
PMC10123586
Introduction
tumor, leukemia, AML, toxicities, ’ comorbidities
LEUKEMIA, ACUTE MYELOID LEUKEMIA, AML, TUMOR
The prognosis of elderly patients with acute myeloid leukemia (AML) is poor because of leukemia characteristics, patients’ comorbidities, and treatment toxicities [The OCV-501, a tumor vaccine, is an HLA class II-binding polypeptide consisting of 16 amino acid residues derived from WT1 protein [
PMC10123586
Materials and methods
PMC10123586
Study design and patients
AML
AML
Among 134 patients who were randomized in the multicenter, randomized, double-blind, placebo-controlled phase II study (ClinicalTrials.gov: NCT01961882), one patient allocated to the OCV-501 group did not receive the study drug, and 28 patients enrolled from overseas institutions were excluded from this study. Of the 1...
PMC10123586
Statistical analysis
death
REGRESSION, RECURRENT DISEASE
DFS was defined as the length of time from the date of vaccination to any recurrent disease or death, whichever occurred first. OS was defined as the length of time from the date of vaccination to death from any cause. Survival curves were estimated using the Kaplan–Meier method and compared using log-rank tests. Univa...
PMC10123586
Results
myelodysplastic syndromes
EVENT, MYELODYSPLASTIC SYNDROMES
The patients’ characteristics are presented in Supplementary Table 1. The 5-year DFS rate (95% confidence interval, 95%CI) was 36.0 (22.8–49.3)% in the OCV-501 group and 33.7 (20.2–47.8)% in the placebo group, indicating no significant difference (DFS We analyzed the effect of vaccination on peripheral (aNext, we analy...
PMC10123586
Discussion
AML
REMISSION, AML
This study revealed that 1) there was no prognostic difference between the OCV-501 and placebo groups even on long-term follow-up, 2) Although the first finding is disappointing, the modest suppression of peripheral The third finding regarding IgG reactivity is a characteristic observed with this helper peptide. The mo...
PMC10123586
Acknowledgements
Cancer
ACUTE MYELOID LEUKEMIA, CANCER
We would like to express our gratitude to Prof. Haruo Sugiyama for his suggestion of this study and data analysis. We thank Mr. Nobuhito Sanada, Ms. Akiko Kageyama, and Mr. Junji Ikeda (Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan) for their helpful advice on the data of "multicenter, randomized, placebo-controlled, d...
PMC10123586
Author contributions
All authors contributed to the study conception and design. Data collections were performed by all authors except TN and AS. Data management and analysis were done by TN and AS. The first draft of the manuscript was written by AS and TN, and all authors commented on previous versions of the manuscript. All authors read...
PMC10123586
Funding
Cancer
CANCER
This study was funded by Cancer Immunology Laboratory Co., Ltd. (Osaka, Japan).
PMC10123586
Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
PMC10123586
Declarations
PMC10123586
Conflict of interest
Financial interests: Tomoki Naoe has received speaker honoraria from Astellas, Otsuka, Nippon-Shinyaku, Pfizer, Bristol-Myers Saquibb and Sysmex. Nahoko Hosono has received honorarium from Abbvie GK. Mizuki Ogura has received honorarium from Nippon Shinyaku, Chugai, and AstraZeneca. Kensuke Usuki has received research ...
PMC10123586
Ethical approval
This study was performed in line with the principles of the Declaration of Helsinki and Ethical Guidelines for Medical and Health Research Involving Human Subjects established by the Ministry of Health, Labor and Welfare. The protocol was approved by the Ethics Committee of NHO Nagoya Medical Center (Dec. 03. 2021/No. ...
PMC10123586
Consent to participate
Since this study was an academic study using only existing clinical information without acquiring new materials or information, written or verbal consent was not required from the research subjects. Information about the research was posted on the hospital website, and research subjects were guaranteed an opportunity t...
PMC10123586
Consent for publication
Not applicable to this article.
PMC10123586
References
PMC10123586
ABSTRACT
PMC10327519
Background
Because betaine (BET) supplementation may improve muscular strength and endurance, it seems plausible that BET will also influence CrossFit performance (CF).
PMC10327519
Purpose
SECONDARY
The aim of this study was to evaluate the effects of three weeks of BET supplementation on body composition, CF performance, muscle power in the Wingate anaerobic test (WAnT), and the concentrations of selected hormones. The secondary aims were to analyze the effectiveness of two different BET doses (2.5 and 5.0 g/d) a...
PMC10327519
Methods
BLOOD
The study was designed in a double-blinded randomized cross-over fashion. Forty-three CF practitioners completed the entire study. CF performance was measured using the Fight Gone Bad (FGB) workout and muscle power was evaluated in a 30-second WAnT. Body composition was determined by air-displacement plethysmography. B...
PMC10327519
Results
FGB total improved with BET by 8.7 ± 13.6% (
PMC10327519
Conclusions
BET supplementation may improve CF performance and increase testosterone concentration. However, there was no evidence of a difference between dosages (2.5 and 5.0 g/d) and
PMC10327519
KEYWORDS
PMC10327519
Introduction
SECONDARY, INSULIN RESISTANCE
CrossFit (CF) is a relatively new training program with the goal of optimizing all aspects of physical capacity and performance. Daily workouts include strength, gymnastic, and endurance exercises that engage both aerobic and anaerobic energy systems in the body [The mechanisms of BET’s potential ergogenicity remain in...
PMC10327519
Methods
PMC10327519
Study design
POLAND
The study was designed as a double-blind, randomized, placebo-controlled crossover trial. To investigate the effects of BET supplementation, 43 participants were randomly divided into two parallel groups: one (The participants attended four study meetings at the Department of Human Nutrition and Dietetics and the Cente...
PMC10327519
Participants
POLAND, CHRONIC DISEASES
Fifty-five participants were initially enrolled to participate in this study. A total of 43 completed the entire study protocol and were included in analyses. The participants recreationally and regularly trained in CF at different gyms in Poznan, Poland. The criteria for qualifying for the study included good health, ...
PMC10327519
Supplementation
POLAND
Participants were randomly allocated to a group receiving either 2.5 or 5.0 g/d BET. BET was administered in the form of cellulose capsules (Medicaline, Konrad Malitka, Poland), each containing 500 mg BET. PL was administered in identical-looking white capsules containing cellulose. Participants receiving a daily dose ...
PMC10327519
Body composition
fat-free mass, FM
THORACIC
Body composition was measured fasted in the morning based on air displacement plethysmography using a Bod Pod (Cosmed, Italy). Once the body density had been determined, the fat mass (FM) and fat-free mass (FFM) were calculated using the Siri equation. Thoracic lung volume was estimated using the Bod Pod software. Duri...
PMC10327519
Anaerobic capacity measurement
Anaerobic capacity was assessed using the classic WAnT test on a cycloergometer (Monark 894E, Varberg, Sweden), following the recommendations for such tests proposed by Bar-Or [
PMC10327519
CF performance
Twenty minutes after the WAnT test, CF performance was measured using the FGB workout, which has been previously described [
PMC10327519
Dietary data
POLAND
Before each study meeting participants completed a three-day food diary. Participants received detailed instructions on the type of food and drink consumed, time of food consumption, culinary techniques, and recipes (which should be recorded using household measures). Food diaries were then analyzed for nutrient intake...
PMC10327519
Blood collection and analysis
Tecan
Vein blood was collected in the morning of each study meeting in a fasted state by certified personnel. After centrifugation, plasma was stored at −80°C until needed for analysis. Selected hormone concentrations in the plasma were determined using commercially available ELISA kits: EIA1887 for cortisol, EIA4140 for ins...
PMC10327519
MTHFR genotyping
BLOOD
Blood samples for
PMC10327519
Statistical analysis
Data normality was evaluated with the Shapiro – Wilk test. A series of within/between-subject repeated measure analyses of variance (ANOVA) in a general linear model was used to compare measurements of performance, muscle power, body composition, and hormone concentrations. The within factors were treatment (BET and PL...
PMC10327519
Results
MP, FM
Out of 84 participants screened for eligibility, 31 were excluded (22 did not meet inclusion criteria, 19 declined to participate). Fifty-five were randomized and allocated to 2.5 g/d BET and 5.0 g/d BET. Forty-three participants attended all four study meetings and were analyzed. Eleven participants dropped out of the...
PMC10327519
Discussion
dehydration, FM, MP, muscle hypertrophy
DEHYDRATION
Our results showed that BET significantly improved CF performance, which was the main outcome of the study. Specifically, BET increased the number of repetitions in all three rounds of FGB separately and also for total FGB score. There is only one other study of BET supplementation in CF [Even though BET improved CF pe...
PMC10327519
Supplementary Material
PMC10327519
Supplemental Material
Click here for additional data file.
PMC10327519
Acknowledgment
The authors express their gratitude to all the participants in this study.
PMC10327519
Disclosure statements
No potential conflict of interest was reported by the author(s).
PMC10327519
Author contribution
KDM
EZ, KDM, and AC developed the research concept and design; EZ, KDM, MS, and NG collected the data; EZ analyzed and interpreted the data; EZ wrote the manuscript; AC and KDM revised the manuscript. All authors accepted the final version of the manuscript and agreed to be accountable for all aspects of the work.
PMC10327519
Ethics approval
POLAND
The study was approved by the local ethical committee (Bioethics Committee at Poznan University of Medical Sciences, Poznan, Poland. Decision no. 1092/17, 9 November 2017) and written informed consent was obtained from all participants before the study began. All procedures were conducted in accordance with the ethical...
PMC10327519
Supplementary material
Supplemental data for this article can be accessed online at
PMC10327519
References
PMC10327519
Abstract
hypoalgesia, pain
SECONDARY
We aimed to compare the effects of three intensities of treadmill running on exercise‐induced hypoalgesia (EIH) in healthy individuals. We anticipated that the primary and secondary changes in pain perception and modulation may differ between running intensities. Sixty‐six women were randomly assigned to one of three t...
PMC10519819
INTRODUCTION
high‐intensity, pain
SECONDARY, SYNDROMES
Exercise has been identified as an effective intervention for managing patients with pain syndromes. Previous studies have demonstrated that global aerobic exercises (Vaegter et al., The analgesic effect following exercise in asymptomatic individuals tends to be correlated with exercise intensities (Baiamonte et al., T...
PMC10519819
METHODS
This study was approved (2023023H) by the Sports Science Experimental Ethics Committee of Beijing Sport University.
PMC10519819
Study design
Sixty‐nine healthy participants were included in this study and invited to perform exercise interventions of different intensities. Informed consent forms were provided and signed by all participants before participating in this study. Demographic data and baseline measurements (such as resting heart rate [HRrest], PPT...
PMC10519819
Participants
fatigue, heart disease, pain
SYNDROME, HEART DISEASE
Based on previous studies (Hviid et al., Sixty‐nine healthy female students (aged 18–30 years) from Beijing Sport University were included in this study, 66 of whom were enrolled. The exclusion criteria were: (1) pain‐related pathological or psychological syndrome within 3 months; (2) injury history of lower extremitie...
PMC10519819
Procedures
All participants performed a single treadmill running session at different intensities based on their THR. The THR was 40% HRR in group A, 55% in group B, and 70% in group C. The participants wore an HR belt to monitor and record the real‐time HR during the test and running sessions. A running assessment was administer...
PMC10519819
Outcome measures
STERILE, COLD
Outcome measures were assessed at multiple time points: before, during, and after the running session. The PPT‐arm and PPTol were recorded at every interval during running, and the PPT‐leg was only tested after the running session. CPM responses were evaluated using cold pressure methods at baseline and 24 h after the ...
PMC10519819
Pressure pain threshold
pain
Pressure pain threshold was evaluated using a quantitative sensory testing protocol (Wytrazek et al., 
PMC10519819
Pressure pain tolerance threshold
pain
Pressure pain tolerance threshold was assessed using a quantitative sensory testing protocol (Bellomo et al., 
PMC10519819
Conditional pain modulation
COLD
The CPM response was measured using a quantitative sensory testing protocol, specifically the cold pressor procedure (Coulombe‐Leveque et al., 
PMC10519819
Statistical analysis
The normality of all data was assessed using the Shapiro–Wilk test. Differences in baseline data (height, weight, HRrest, CPM, PPT, and PPTol) between the groups were analyzed using one‐way analysis of variance (ANOVA). To determine the differences among the three groups over time (running times and acute follow‐up tim...
PMC10519819
RESULTS
PMC10519819
Baseline and running characteristics
shoulder pain, pain
SYNDROME
Three participants were excluded from this study because shoulder pain syndrome occurred 1 month before the experiment. Of the 66 participants enrolled in this study, 19 in group A completed low‐intensity running for 30 min, 21 in group B completed moderate‐intensity running for 30 min, and 20 in group C completed high...
PMC10519819
Changes in pressure pain threshold of the arm following running
pain
Two‐way repeated‐measures ANOVA revealed significant main effects (Two‐way repeated‐measures ANOVA revealed significant main effects (One‐way ANCOVA revealed significant between‐group differences (Changes in PPT of arms following running. All data were presented as mean and standard deviation; PPT, pressure pain thresh...
PMC10519819
Changes in pressure pain threshold of the leg following running
pain
Two‐way ANCOVA revealed significant between‐group differences (Two‐way repeated‐measures ANOVA revealed significant main effects (One‐way ANCOVA revealed significant between‐group differences (Changes of PPT in legs following running. All data were presented as mean/standard deviation; PPT, pressure pain threshold. *PP...
PMC10519819
Changes in pressure pain tolerance threshold following running
pain
Two‐way repeated‐measures ANOVA revealed significant main effects (Two‐way repeated‐measures ANOVA revealed significant main effects (One‐way ANCOVA revealed significant between‐group differences (Changes in PPTol following running. All data were presented as mean/standard deviation; PPTol, pressure pain tolerance thre...
PMC10519819
Changes in conditional pain modulation following running
pain
One‐way ANCOVA revealed significant between‐group differences (Changes in CPM following running. All data were presented as mean/standard deviation; CPM, conditioned pain modulation. *CPM in low‐intensity group significantly higher than high‐intensity group.
PMC10519819
DISCUSSION
EIH, muscle soreness, hypoalgesia, pain
HEAT, SECONDARY, CONTRACTION
We investigated the changes in pain perception following running exercises in healthy individuals. Our results revealed that the changes in PPT and PPTol increased with running time. The PPT and CPM responses to moderate‐ and low‐intensity running were significantly higher than those to high‐intensity exercise during t...
PMC10519819
CONCLUSION
hypoalgesia, pain
SECONDARY
Our study revealed that moderate‐ and low‐intensity running induced primary and secondary global hypoalgesia effects and increased CPM responses in females, which may be attributed to the activation of descending pain inhibition, while high‐intensity running only induced limited EIH effects with reduced CPM responses a...
PMC10519819
AUTHOR CONTRIBUTIONS
Zi‐Han Xu and Nan An conceived and designed research, Zi‐Han Xu, Nan An, Jeremy Rui Chang, and Yong‐Long Yang performed experiments, Zi‐Han Xu and Yong‐Long Yang analyzed data. Zi‐Han Xu, Nan An and Jeremy Rui Chang interpreted results of experiments. Zi‐Han Xu prepared Tables and Figures and drafted manuscript. All au...
PMC10519819
FUNDING INFORMATION
This study is self‐funded.
PMC10519819