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Types of studies | Observational studies such as analytical cross-sectional studies, case–control studies, and longitudinal studies (e.g., cohort studies) will be included for information on factors associated with PA participation among children. We will also include experimental study designs such as randomized controlled trials (RCTs). In cases where RCTs are not possible due to the nature of the intervention or due to ethical concerns, we will include the non-randomized trials or the experimental studies not following randomization for the allocation of participants. Additionally, we will also include other non-randomized study designs such as controlled before and after studies (CBAs) and quasi-experimental studies. | PMC10134558 | ||
Conceptual framework | We hypothesize several factors’ direct and indirect effects on PA participation in children through the conceptual framework (Fig. Conceptual Framework of direct and indirect factors effecting PA participation in childrenThe social factors also play an essential role in PA participation [Policy factors are another influence on PA participation behavior and are a crucial feature of public health [ | PMC10134558 | ||
Searching for studies | We will search Medical Literature Analysis and Retrieval System Online (MEDLINE) via PubMed and Web of Science, Scopus, Excerpta Medica Database (EMBASE), Cumulated Index to Nursing and Allied Health Literature (CINAHL), The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), and Physiotherapy Evidence Database (PEDro) for English language publications, published from the inception of the database till November 2021. In addition, we will search the following websites: Australian Association for Adolescent Health ( | PMC10134558 | ||
Selection of studies | Two reviewers (PS and ER) will independently screen the titles and abstracts of potential studies for eligibility based on the eligibility criteria of the review. Any disagreement at this stage will be resolved via discussion or in consultation with the third reviewer (SB). Full texts of all the included studies will be downloaded, and in case of non-available full texts study, authors or subject experts will be contacted for full texts: in case the full text remains unavailable, we will exclude that study. In case of two reports of the same study, the latest and the one with the complete information will be included for full-text and the other report will be marked as a duplicate. In the next step, a full-text screening will be performed by two review authors (PS and ER) independently. Any disagreement during this stage will be resolved by consensus or via contacting the third author (SB). More information about the process of selection of studies is given in Table Screening protocol
B) Does the study involve one of the following designs or analyses: • Analytical cross-sectional studies, case–control studies • Longitudinal studies • Randomized controlled trials, and non-randomized trialsIf the answer is “yes,” go to COR if it is notclearly statedin the abstract, go to CIf the publication is a commentary, perspective, editorial, review, or conference abstract,exclude the studyF) Does the study explains the PAAny physical activity/exercise for a minimum of 60 min in a day for a minimum of 3 days in a week. There is no restriction on the mode and setting of PA. It should include moderate or vigorous activity (causing a noticeable to a substantial increase in HR and breathing, respectively) Activities like such as brisk walking, running, swimming, dancing, and strength training (e.g., tug of war, climbing a tree, or working with Thera bands)If the answer is “yes,” then move to G OR if it is not clearly stated and in doubt:flag for discussion | PMC10134558 | ||
Data management and extraction | Data will be managed using the EndNote reference manager and Microsoft Excel Office software. Data will be extracted by two review authors (PS and ER) independently by using the pre-tested data extraction sheet. All the reviewers will perform pilot testing of the data extraction sheet. Information related to bibliographic details, participants, PA, and outcome details will be extracted. An example of the data extraction form is given in Table Data extraction formatPublication type:Funding sourceList down outcome, variable type: continuous or categorical, type of analysis, effect measures with 95% CI (such as OR, risk ratio, HR)No of participants analyzed, number list to follow-up | PMC10134558 | ||
Critical appraisal of the included studies risk of bias in individual studies | The reviewers will use the Cochrane Risk of Bias (ROB2) for assessing the quality of included RCTs [ | PMC10134558 | ||
Measure of effects | If continuous, data will be reported as mean and standard deviation with a 95% confidence interval (CI). For categorical data, estimates of odds ratio (OR) and risk ratio (RR) with 95% CI will be used for reporting.Odds ratio will be extracted and reported for observational studies where the estimation of risk is difficult, such as analytical cross-sectional studies and case–control studies. Risk ratio (95%CI) will be extracted and reported for longitudinal studies (e.g., cohort studies) and experimental studies (RCTs and NRCTs). The final results will be reported as RR (95% CI), as relative risk or risk ratio is considered as a more intuitive measure of effect and is easy to interpret [ | PMC10134558 | ||
Data synthesis | PMC10134558 | |||
For primary objective | Findings of the review will be presented via “the characteristics of included studies” and “summary of findings” table (as shown in Table 0 to 40%: might not be important30 to 60%: may represent moderate heterogeneity50 to 90%: may represent substantial heterogeneity75 to 100%: considerable heterogeneityRandom effects model with and inverse-variance approach, i.e., DerSimonian and Laird method will be used for meta-analysis [A narrative synthesis will be performed in case of high heterogeneity and when meta-analysis is not possible, i.e., due to the presence of “clinical,” “methodological,” and “statistical.” In the narrative synthesis, the outcome and findings will be reported narratively, and tables/figures will be used for explanation.If it is possible, sub-group analyses will be performed based on geographical location, age, gender, type of physical activity, etc. If sufficient data is available, we will perform sensitivity analysis for assessing the robustness of the results. | PMC10134558 | ||
For secondary objective | The primary objective findings, i.e., the factors associated with PA participation among children will be used to frame the policy and practice recommendations. The different factors for PA participation will be listed, based on our contextual framework. Additionally, a list of recommendations present in the available scientific literature will be prepared. These findings will be further discussed with all the relevant stakeholders to frame the appropriate recommendations. | PMC10134558 | ||
Meta-biases | Funnel plots will be used for the identification of reporting or publication bias. The identification of reporting bias will be done based on a visual assessment of the funnel plot, where a symmetrical funnel plot will be interpreted as the absence of reporting bias and an asymmetrical plot will indicate the presence of reporting bias. | PMC10134558 | ||
Discussion | obesity | OBESITY, DISEASES | Physical inactivity is one of the leading risk factors for lifestyle diseases and increased morbidity worldwide. PA is a modifiable factor and increasing PA levels among children can help reduce health risk factors, promote healthy lifestyles, and improve their quality of life.In this review, we expect to identify the factors associated with PA participation among children. We hope that systematically reviewing such factors will help address the paucity of evidence surrounding factors contributing to poor engagement with physical activity, which can lead to obesity and other medical conditions. Identifying the factors influencing PA participation in children and adolescents can provide guidance, health promotion, and resources for the families, policymakers, and authorities to improve the lifestyle and health of young people. Any major changes in the protocol will be amended in PROSPERO. An abstract of the complete synthesis will be presented in relevant conferences. The manuscript will be submitted to a relevant journal for publication. This systematic review will support the caregivers, policymakers, and healthcare providers by summarising the evidence for different behavioral interventions intended to increase the physical activity participation among children. This behavioral change is particularly relevant globally given WHO’s focus on preventing diseases in children.
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Acknowledgements | We would like to acknowledge the Manipal Academy of Higher Education for technological and logistic support. | PMC10134558 | ||
Authors’ contributions | PS and ER conceptualized the topic. PS, ER, and SB drafted the manuscript. PS and ER edited and finalized the final version of the manuscript. All the authors (PS, ER, SB, VK, HVB) read, provided intellectual feedback, and approved the final version of the manuscript. | PMC10134558 | ||
Funding | No financial support from any commercial or non-commercial funders was done to support this systematic review. | PMC10134558 | ||
Availability of data and materials | Data sharing is not applicable to this protocol as datasets are not generated or analysed.
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Declarations | PMC10134558 | |||
Ethics approval and consent to participate | Not applicable. | PMC10134558 | ||
Consent for publication | Not applicable. | PMC10134558 | ||
Competing interests | The authors declare that they have no competing interests. | PMC10134558 | ||
References | PMC10134558 | |||
1. Introduction | obesity, Obesity, weight loss, bodyweight loss | OBESITY, OBESE, OBESITY | Although bariatric surgery is known to change the metabolome, it is unclear if this is specific for the intervention or a consequence of the induced bodyweight loss. As the weight loss after Roux-en-Y Gastric Bypass (RYGB) can hardly be mimicked with an evenly effective diet in The prevalence of obesity has nearly tripled in the last 40 years and continues to increase in many parts of the world [Obesity correlates with an alteration in the small molecules in the fluids and tissues of the body [To identify metabolomic changes induced by RYGB, serum samples of morbidly obese patients treated with bariatric surgery (OP) or psychotherapy-enhanced lifestyle intervention (LS) from the randomized controlled Würzburg Adipositas Study (WAS) were analyzed as well as samples of | PMC9916678 |
2. Results | PMC9916678 | |||
2.1. Participants from the WAS Trial | weight loss | Characteristics of the patient cohort at the start of the study have been described in detail previously [At 1-year follow-up patients of the RYGB-surgery group achieved a significant weight loss of −34.3% (BMI 49.1 [46–51] kg/mA total of 188 metabolites were measured in 46 serum samples at randomization and one year after randomization. Forty-nine metabolites were not considered due to exclusion criteria. Thus, 139 metabolites (9 Cs, 21 amino acids, 9 biogenic amines, 13 lysoPCs, 72 PCs, a hexose and 14 SMs) were valid and retained for the main analysis and the derivation of metabolomic profiles. Fifty-seven metabolites were found to be significantly different between groups (1 acylcarnitine, 13 amino acids, 1 biogenic amine, 5 lysoPCs, 31 PCs, 5 SMs and a hexose) as shown in The performed principal component analysis (PCA) resulted in twelve discriminating components with an eigenvalue > 1. The first two components explained 49% of the variance. Hence, further investigation was performed based on a two-component model. The first principal component (PC1) was characterized predominantly by phosphatidylcholines and sphingolipids, whereas the second principal component (PC2) was characterized by BCAA, aromatic acids and acylcarnitines (see We performed hierarchical clustering of the 57 metabolites with significant differences between the LS and OP group (see | PMC9916678 | |
2.2. Rodent Model | Characteristics of the rodent model have been described in detail previously [Further analysis of these metabolites (2 acylcarnitines, 6 amino acids, 2 biogenic amine, 3 lysoPCs, 41 PCs and 8 sphingolipids) with PCA showed that the first two components explained 74% of the variance. PC1 was mainly characterized by phosphatidylcholines. PC2 was not characterized by a specific subgroup of metabolites (see We performed hierarchical clustering of the 62 metabolites with significant differences between the RYGB_rat and the BWM_rat group (see | PMC9916678 | ||
2.3. Analysis of Overlapping Metabolomic Profiles in the Human OP and the Rat RYGB Group | Thirty-one metabolites with significant differences in both OP vs. LS and RYGB_rat vs. BWM_rat could be identified (see In terms of individual metabolites, six amino acids with a significant difference between RYGB_rat and BWM_rat were also found to be significantly different in the Analyzing the phosphatidylcholines with ester bonding, eleven PCs could be identified to be significantly different in both comparisons: PC aa C32:0 (16.0 µM in LS vs. 18.5 µM in OP; 5.7 µM in BWM_rat vs. 11.4 µM in RYGB_rat), PC aa C34:1 (257 µM in LS vs. 283 µM in OP; 66 µM in BWM_rat vs. 106 µM in RYGB_rat), PC aa C38:1 (0.62 µM in LS vs. 0.97 µM in OP; 0.43 µM in BWM_rat vs. 1.08 µM in RYGB_rat), PC aa C38:5 (44.1 µM in LS vs. 52.1 µM in OP; 24.3 µM in BWM_rat vs. 40.5 µM in RYGB_rat), PC aa C40:2 (0.16 µM in LS vs. 0.19 µM in OP; 0.26 µM in BWM_rat vs. 0.51 µM in RYGB_rat) and PC aa C40:5 (6.5 µM in LS vs. 8.0 µM in OP; 5.7 µM in BWM_rat vs. 9.2 µM in RYGB_rat).Five of these PCs are characterized by forty-two carbon atoms (PC aa C42:Y): PC aa C42:0 (0.29 µM in LS vs. 0.35 µM in OP; 0.06 µM in BWM_rat vs. 0.10 µM in RYGB_rat), PC aa C42:1 (0.13 µM in LS vs. 0.16 µM in OP; 0.08 µM in BWM_rat vs. 0.11 µM in RYGB_rat), PC aa C42:4 (0.09 µM in LS vs. 0.12 µM in OP; 0.13 µM in BWM_rat vs. 0.20 µM in RYGB_rat), PC aa C42:5 (0.21 µM in LS vs. 0.28 µM in OP; 0.13 µM in BWM_rat vs. 0.28 µM in RYGB_rat) and PC aa C42:6 (0.24 µM in LS vs. 0.29 µM in OP; 0.31 µM in BWM_rat vs. 0.49 µM in RYGB_rat).Twelve phosphatidylcholines with ether bonding were found to be significantly different in the Finally, two out of five sphingolipids with a significant difference in the | PMC9916678 | ||
3. Discussion | obesity, weight loss | OBESITY, SEPARATION | The aim of our study was to identify and characterize a comprehensive metabolomic profile, which highlights the effect of bariatric surgery on the metabolome beyond weight loss. Whereas patients of the WAS intensified lifestyle group failed to lose weight significantly, patients with bariatric surgery lost a significant amount of their body weight as expected. To clarify the role of RYGB-induced body weight loss itself, the same metabolomic parameters were analyzed in rats treated with RYGB or a similar effective food restriction regime.Examining the Sphingolipids maintain lipid microenvironments of plasma membranes and form lipid rafts [A further metabolomic subgroup included BCAA, and aromatic amino acids. The BCAAs could be identified as a valid separator of the LS and OP group at one year after randomization. As described before, BCAAs correlate with BMI and HOMA-IR [Analyzing overlapping phosphatidylcholines from the metabolomic profiles as a translational approach with indirect comparison, PC aa C42:Ys have been identified as being significantly different metabolites in both comparisons, OP vs. LS and RYGB_rat vs. BWM_rat. PC aa C42:Ys, better known as lecithins, have been repeatedly mentioned in studies investigating metabolomics in obesity [The analysis of the metabolomics of rats with similar body weights after RYGB and diet restriction and similar food composition overcomes the limitation that weight loss effects cannot be differentiated from the effects of the bariatric intervention (i.e., changed absorbance) itself. Interestingly, lipids play a crucial role in differentiating RYGB from BWM rats, while amino acids do not facilitate the separation of these intervention groups. Therefore, changes in BCAAs after RYGB do not seem to be caused by bariatric surgery itself. A significant increase in sphingolipids as well as PC aa C42:Ys in the OP group of the WAS trial and higher levels in the BWM vs. RYGB group of our animal experiment were detected. The role of sphingolipids in obesity and IR is not fully understood and has to be investigated in further Our study has several limitations. The very low sample size compared to the large number of analyzed metabolites may have hampered the interpretation of data. It was also not possible to consider the whole spectrum of confounders (e.g., smoking status) potentially influencing the metabolic spectrum. Although there was no difference in the nutrition counseling, we cannot exclude that the actual nutrition might have differed from the references within the nutrition counseling. Additionally, gender distribution differed significantly between the LS and OP group of the WAS cohort. Furthermore, a direct comparison of | PMC9916678 |
4. Materials and Methods | PMC9916678 | |||
4.1. Patients | OBESE | The Würzburg Adipositas Study is a randomized trial comparing the effects of RYGB vs. psychotherapy-enhanced lifestyle intervention not including calorie-limited nutrition in morbidly obese patients. Details of the design of the study are published elsewhere [ | PMC9916678 | |
4.2. Animals | As described in detail elsewhere, adult male Wistar | PMC9916678 | ||
4.3. Laboratory Measurements | In brief, serum samples from patients were obtained upon enrolment under standardized conditions. After an overnight fast, the blood was drawn from the cubital vein with a Safety-MultiflyPlasma samples from | PMC9916678 | ||
4.4. Targeted Metabolomics | Reagents, standards and controls were prepared according to manufacturer’s instructions (Biocrates UM-P180-SCIEX-13) for mass spectrometry. Analytical columns (Acquity UPLC BEH C18 1.7 µm 2.1 mm × 75 mm, Waters) and pre-column (Acquity BEH C18 1.7 VANGUARD) from Waters (Eschborn, Germany) were used. Targeted metabolomics was performed using the AbsoluteIDQ p180 Kit (BIOCRATES Life Sciences AG, Innsbruck, Austria) [Serum from each sample was processed according to the manufacturer’s recommendations. In brief, 10 μL of the internal standard solution was added to each well on a filter spot of the 96-well extraction plate. After drying under a gentle stream of nitrogen, 10 μL of each serum sample, quality control (QC) sample, blank, zero sample or calibration standard, was added to the appropriate wells. The plate was then dried under a gentle stream of nitrogen. Derivatization was performed using 5% phenyl isothiocyanate (33% ethanol, 33% water, 33% pyridine). Samples were incubated for 20 min followed by extraction with methanol. Electrospray ionization (ESI)—LC-MS/MS and flow injection (FIA) MS/MS was performed on Sciex 4500QTRAP MD (SCIEX, Framingham, MA, USA). MS-system was coupled to an Agilent 1290 UHPLC-system (G4226A autosampler, infinity BinPump, G1316C column-oven, G1330B thermostat (Agilent, Santa Clara, CA, USA)).Data were processed with Analyst Software version 1.6.2 MD (SCIEX, Framingham, MA, USA). LC- and MS/MS settings were set according to the manufacturer’s manual. MetIDQ software (5.5.4-DB 100 Boron-2623 (Biocrates, Innsbruck, Austria)) was used for validation and processing of MS data. Amino acids and biogenic amines were separated by UHPLC before injection into the mass spectrometer, while flow injection analysis was used for PCs, hexose, Cs and SMs. In this dataset, metabolites with more than 60% measurements at the limit of detection (LOD) or below lowest limit of quantification (LLOQ), and those samples with missing values for more than 60% of the metabolites were excluded from the analyses as described previously [ | PMC9916678 | ||
4.5. Statistical Analysis | Analyses were conducted using SPSS software (PASW version 25.0, SPSS Inc. Chicago, IL, USA), GraphPad Prism version 9.1.2 for Windows (GraphPad Software, La Jolla, CA, USA) and MetaboAnalyst (version 5.0, Clinical data of the WAS cohort was not normally distributed (Shapiro–Wilk test, Data in the rodent model were normally distributed (Shapiro–Wilk test, | PMC9916678 | ||
5. Conclusions | OBESE | We analyzed the effects of surgical vs. lifestyle intervention on the serum metabolome of obese and insulin resistant | PMC9916678 | |
Supplementary Materials | The following supporting information can be downloaded at: Click here for additional data file. | PMC9916678 | ||
Author Contributions | Conceptualization, U.D., I.B. and M.F.; methodology, M.K. and I.B.; software, M.K. and U.D.; validation, U.D., M.K. and M.F.; formal analysis, I.B.; investigation, U.D.; resources, M.F., A.-C.K., C.S. and U.D.; data curation, M.K.; writing—original draft preparation, I.B.; writing—review and editing, U.D., M.F., M.K., A.-C.K. and C.S.; visualization, I.B.; supervision, U.D. and M.F.; project administration, M.F.; funding acquisition, M.F and A.-C.K. All authors have read and agreed to the published version of the manuscript. | PMC9916678 | ||
Institutional Review Board Statement | The WAS study was conducted in accordance with the Declaration of Helsinki, and approved by the Ethics Committee of the University Hospital of Wuerzburg (182/08, approved on 16 December 2014). The rodent model was conducted according to the guidelines of the Declaration of Helsinki and approved by the local regulatory authority (Regierung von Unterfranken, Wuerzburg, Germany, AZ: 55.2-2532-2-467). All experiments were performed in accordance with German and European laws and regulations (TierSchG, TierSchVersV, Directive 2010/63/EU). | PMC9916678 | ||
Informed Consent Statement | Informed consent was obtained from all subjects involved in the study. | PMC9916678 | ||
Data Availability Statement | Data are contained within the article or | PMC9916678 | ||
Conflicts of Interest | The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. | PMC9916678 | ||
References | Unsupervised principal component analysis of 57 significantly different metabolites between lifestyle intervention and surgery group in the WAS cohort at 1-year follow-up. The first component explains 32% of the variation, and the second component 17%. C, acylcarnitine; lysoPC, lysophosphatidylcholine; PC aa, phosphatidylcholine with ester bonding; PC ae phosphatidylcholine with ether bonding; SM, sphingolipid.Heat map showing the scaled relative abundance of metabolites, which were significantly different between LS and OP group at one-year follow-up, visualized by hierarchical clustering. Abundance values represent row-wise z-scores of read counts. Each bar in the horizontal columns (which represent different patients) represents the expression intensity. Blue indicates a decreased level, red indicates an increased level. C, acylcarnitine; lysoPC, lysophosphatidylcholine; PC aa, phosphatidylcholine with ester bonding; PC ae phosphatidylcholine with ether bonding; SM, sphingolipid.Unsupervised principal component analysis of significantly different metabolites (n = 62) between BWM and RYGB rats. The first component explains 52% of the variation, and the second component 22%. C, acylcarnitine; lysoPC, lysophosphatidylcholine; PC aa, phosphatidylcholine with ester bonding; PC ae phosphatidylcholine with ether bonding; SM, sphingolipid.Heat map with the scaled relative abundance of 62 significantly different metabolites in BWM and RYGB rats four weeks postoperative visualized by metabolite hierarchical clustering. Abundance values represent row-wise z-scores of read counts. Each bar in the horizontal columns (which represent different rats) represents the expression intensity. Blue indicates a decreased level, red indicates an increased level. C, acylcarnitine; lysoPC, lysophosphatidylcholine; PC aa, phosphatidylcholine with ester bonding; PC ae phosphatidylcholine with ether bonding; SM, sphingolipid.Metabolomic profile of 57 significantly different metabolites of acylcarnitines; amino acids; lysophosphatidylcholines; sphingolipids; acylcarnitines; biogenic amines; phosphatidylcholines with ester bonding; phosphatidylcholines with ether bonding; hexose, between lifestyle (LS) and RYGB (OP) group at one-year follow-up.Metabolomic profile of 62 significantly different parameters of amino acids; lysophosphatidylcholines; sphingolipids; acylcarnitines; phosphatidylcholines with ester bonding; phosphatidylcholines with ether bonding, between rats with RYGB and rats with diet restriction (BWM) four weeks after start of the interventions.Time schedule of the WAS trial. R, randomization.Medians ± interquartile range (IQR) of baseline characteristics with standard deviation of patients enrolled in the WAS trial.One-year follow-up means of 57 significantly different metabolites between LS and OP with standard deviation. Means of 62 significantly different metabolites at four weeks after start of the interventions between BWM_rat and RYGB_rat with standard deviation. Eighty-one significantly different metabolites subsequently in LS vs. OP of the WAS cohort at one-year follow-up and in animals treated with RYGB vs. diet-restricted animals of the rat cohort four weeks after start of the interventions. Thirty-one overlapping metabolites found to be significant in both comparisons are printed in bold. Arrows indicate if the metabolite is increased or decreased in the respective surgical group in comparison the conservative group. C, acylcarnitine; lysoPC, lysophosphatidylcholine; PC aa, phosphatidylcholine with ester bonding; PC ae phosphatidylcholine with ether bonding; SM, sphingolipid. | PMC9916678 | ||
2. Materials and Methods | PMC10384820 | |||
2.1. Study Design | This was an assessor-blind three-armed randomized controlled trial (clinicaltrials.gov number: NCT05680467) conducted under the supervision of the Department of Physiotherapy of the International Hellenic University during the period December 2022–March 2023. Ethical approval was granted by the Ethics Committee of the Department of Physiotherapy of the International Hellenic University (No. EC-06/2022). Sixty participants with CNSLBP were recruited from two outpatient clinics and were randomly divided into three groups (two intervention and one control) of 20 participants each. The distribution of participants was performed with the Research Randomizer computer software (version 4) [ | PMC10384820 | ||
2.2. Participants | diagnosed neurodegenerative diseases, neuropathic pain, Pain, epilepsy, cancer, fracture, systemic musculoskeletal diseases, psychiatric, Parkinson’s, trauma | CANCER, NERVE ROOT COMPRESSION, DISORDERS, EPILEPSY | The inclusion criteria of the participants were (1) duration of symptoms longer than 12 weeks, (2) Numeric Pain Rating Scale (NPRS) score higher than 3 during the baseline assessment, and (3) written consent to participate in the research. The exclusion criteria of the participants were (1) neuropathic pain extending along the lower limb due to nerve root compression, (2) previous spine surgery, (3) history of spine trauma or fracture, (4) implanted pacemakers, (5) pregnancy, (6) cancer, (7) systemic musculoskeletal diseases, (8) diagnosed neurodegenerative diseases (e.g., Parkinson’s), (9) epilepsy, and (10) history of psychiatric disorders. | PMC10384820 |
2.3. Outcome Measures | The following measurements were performed at the beginning (baseline), after two weeks, and at a one-month follow-up. Participants of both intervention groups attended a total of six sessions (three sessions per week). Each session lasted 30 min. All outcome measurements were considered primary. | PMC10384820 | ||
2.3.1. Pain with the Numeric Pain Rating Scale (NPRS) | pain | The NPRS is an 11-point pain scale numbered from 0 to 10. The left end of the scale is marked 0 with the phrase “no pain at all”, while the right end is marked 10 with “worst possible pain”. Therefore, a higher value corresponds to more intense pain [ | PMC10384820 | |
2.3.2. Functional Ability with the Roland–Morris Disability Questionnaire (RMDQ) | low back pain, disability | The disability of participants related to CNSLBP was evaluated with the Greek version of the Roland–Morris Questionnaire (RMDQ). The RMDQ consists of 24 questions related to daily activities that patients often report difficulty performing due to low back pain [ | PMC10384820 | |
2.3.3. Pressure Pain Threshold (PPT) with Pressure Algometry | sacroiliac joints, pain | Pressure pain threshold (PPT) is defined as the minimal amount of pressure that produces pain. The PPT assessment was performed with a digital algometer (Wagner FPX 25 Digital Algometer; Wagner Instruments, Greenwich, CT, USA) bilaterally in the quadratus lumborum muscle, in the sacroiliac joints, and paravertebrally in the L4-L5 intervertebral space. The metal rod of the algometer was placed vertically on the site and the examiner applied gradually increasing pressure at a rate of 1 kg/s. The PPT was calculated in kg/cm | PMC10384820 | |
2.3.4. Lumbo-Pelvic Region Mobility with the Fingertip-to-Floor (FTF) Test | lumbar spine flexion | Changes in the lumbar spine flexion range of motion were evaluated with the Fingertip-To-Floor (FTF) test [ | PMC10384820 | |
2.4. Experimental Protocols | PMC10384820 | |||
2.4.1. Manual Therapy (MT) Protocol | The protocol included the application of a series of MT soft tissue techniques for the lumbar area as suggested by Kaltenborn [ | PMC10384820 | ||
2.4.2. Manual Therapy with TECAR (MT + TECAR) Protocol | TECAR | The participants of this group followed the same MT protocol as the first group with the addition of high-frequency current with the WinBack—TECAR device (WINBACK 3SE, Villeneuve Loubet, France). Soft tissue mobilization manipulations were applied in combination with a capacitive conventional electrode (6 cm diameter) and a special electrode bracelet that made the therapist’s own hand function as a resistive electrode. The frequency of the high-frequency current was 500 kHz, while a flexible self-adhesive ground electrode (10 cm × 18 cm) was used as a reference electrode and placed on the abdomen. The application of manual therapy protocol with TECAR is shown in | PMC10384820 | |
2.4.3. Control | pain | Participants in this group received general instructions about managing their back pain and counseling about avoiding activities that may worsen their symptoms. | PMC10384820 | |
2.5. Sample Size Determination | A total sample size of at least 45 subjects was calculated based on an a priori power analysis (G*Power 3.0.10). As a basic prerequisite for this calculation, the power (1-β) was set at 95% and the detection of a difference in the order f = 0.5 (Cohen’s f) [ | PMC10384820 | ||
2.6. Statistical Analysis | Data were analyzed using SPSS Statistics for Windows, version 25.0 (SPSS Inc., Chicago, IL, USA). Normal distribution was checked using the Shapiro–Wilk test and Q-Q and P-P plots. To analyze the data, a two-way analysis of variance (ANOVA) with repeated measures was conducted. The ANOVA was applied to examine the interaction effect between the “Group” and “Time of measurement” factors. The “Group” factor was tested at three levels: manual therapy (MT) group, manual therapy plus TECAR (MT + TECAR) group, and control group. The “Time of measurement” factor was tested at three levels: baseline, second week, and one-month follow-up. If the interaction was statistically significant, the simple main effects were reported using Tukey’s post hoc test (HSD). Intention-to-treat analysis was conducted on all participants in their assigned group to ensure randomization and counter any dropout effect. In case of a dropout, previous time point values were used instead. The significance level was set at | PMC10384820 | ||
3. Results | During December 2022, a total of 78 persons were screened for eligibility. Sixty of them (76.9%) met the inclusion criteria and were randomly allocated into one of the three groups ( | PMC10384820 | ||
3.1. NPRS Score | The statistical analysis revealed a significant interaction effect between “Group” and “Time” for the NPRS score in the two-way ANOVA analysis ( | PMC10384820 | ||
3.2. RMDQ Score | The statistical analysis revealed a significant interaction effect between “Group” and “Time” for the RMDQ score in the two-way ANOVA analysis ( | PMC10384820 | ||
3.3. PPT of L4-L5 Paraspinal Intervertebral Space | The statistical analysis revealed a significant interaction effect between “Group” and “Time” for the right PPT of L4-L5 paraspinal intervertebral space in the two-way ANOVA analysis ( | PMC10384820 | ||
3.4. Sacroiliac Joint PPT | The statistical analysis revealed a significant interaction effect between “Group” and “Time” for the right PPT of the sacroiliac joint in the two-way ANOVA analysis ( | PMC10384820 | ||
3.5. Quadratus Lumborum Muscle PPT | The statistical analysis revealed a significant interaction effect between “Group” and “Time” for the right quadratus lumborum muscle PPT in the two-way ANOVA analysis ( | PMC10384820 | ||
3.6. FTF Test Score | The statistical analysis revealed a significant interaction effect between “Group” and “Time” for the FTF test score in the two-way ANOVA analysis ( | PMC10384820 | ||
4. Discussion | tightness, low back pain, sacroiliac joint dysfunction, pain | HEAT, BENDING, SACROILIAC JOINT DYSFUNCTION | In our research, the same MT protocol was applied with and without the application of a TECAR high-frequency current to investigate whether the simultaneous application of the two methods could be more effective, compared to the individual application of MT, in the treatment of symptoms in people with CNSLBP. Modern TECAR devices are widely accepted in clinical practice, allowing the simultaneous application of high-frequency current with special electrodes, along with therapeutic applications, such as manipulation, mobilization, or therapeutic exercise. However, their efficacy has not been proven in clinical studies. Research data surrounding the applications of TECAR both in the treatment of CNSLBP [The mechanisms to achieve analgesia are known. In manual therapy, the therapeutic manipulations are able, through the mobilization of the tissues and stimulation of the sensory receptors, to block the noxious stimuli of the pain receptors and simultaneously increase the local circulation, the temperature, and the local metabolism at the cellular level [On the other hand, the high-frequency current emitted by a TECAR device produces an intense thermal effect at different tissue levels (muscles, tendons, cartilage, joints, and bones). Generating this deep heat through radio frequency emission has been shown to greatly increase cellular metabolism and provide intense analgesic effects and healing action, which leads to reduced recovery time [The study was conducted on the assumption that the simultaneous emission of the high-frequency current with another means such as the therapeutic manipulations of the care provider combines the therapeutic effects of manual therapy with the effect of deep heat and possibly enhances the analgesic effect. By maintaining consistent conditions throughout the application of the ΜΤ protocol, both with and without the application of TECAR therapy, and at the same time by ensuring sample homogeneity in terms of initial measurements and demographic characteristics, any distinction between the groups can be attributed to the cumulative impact of the MT and TECAR therapeutic means.The results of this research show that the application of the same MT protocol using a conventional capacitive and a resistive electrode bracelet further improved the pain of participants. The NPRS score improved significantly in both intervention groups compared to the control group in the second week, while this difference was maintained at the one-month follow-up (Our results agree with those of Tashiro et al. [Corresponding differences between the groups were also noted in the RMDQ score. Both intervention groups showed statistically significant differences compared to the control group from the second week. These differences remained statistically significant during the one-month follow-up measurement. A difference was also found from the second week between the two intervention groups with the MT + TECAR group showing an improvement in the score compared to the initial measurement by 51.91% (6.1 points decrease) compared to the MT group which improved by 36.4% (4.15 points decrease). However, the differences between the two intervention groups appeared statistically significant only at the one-month follow-up with bigger mean differences between groups at the one-month follow-up related to the second week (3.05 and 2.6, respectively). This fact can be partially explained by the generally lower levels of pain experienced after the intervention by the participants of the MT + TECAR group compared to the participants of the MT group, which is also reflected by the results of the NPRS score. The difference between the two intervention groups at the one-month follow-up is also clinically significant. According to Ostelo et al. [Regarding the PPT values of the L4-L5 paraspinal intervertebral space on the right side, statistically significant differences were detected between the two intervention groups and the control group in the second week, while at the one-month follow-up, differences were detected only between the MT + TECAR group and the control group. A possible explanation is the greater increase in the PPT value noted in the MT + TECAR group compared to the other two groups. It appears that even if the difference between the two intervention groups in the second week did not appear statistically significant, the improvement in the MT + TECAR group was maintained at high levels one month later in contrast to the MT group. This possibly explains why the MT group did not show statistically significant differences compared to the control group at the one-month follow-up (Concerning the L4-L5 paraspinal intervertebral space PPT on the left side, in the second week, differences were detected between the two intervention groups as well as between the MT + TECAR group and the control group, which remained statistically significant during the one-month follow-up (Regarding the sacroiliac joint PPT on both the right and left sides, the only differences noted in the second week were between the MT + TECAR group and the control group. In fact, these differences remained statistically significant during the one-month follow-up, which means that the improvement noted in the participants of the MT + TECAR group (shown numerically in The improvements observed in the PPT values in both the L4-L5 paraspinal intervertebral space and the sacroiliac joint in the participants of the MT + TECAR group appear to be due to the combined effect of MT and TECAR. It is possible that the combination of mechanical (MT) and thermal (TECAR) effects at the same time increased the PPT values more effectively and for a longer period.Regarding the quadratus lumborum muscle PPT, both on the right and left sides, differences between the groups were detected in the second week between the two intervention groups and the control group, while these differences remained statistically significant at the one-month follow-up. However, although Finally, the results of the FTF test score showed that it improved significantly in both intervention groups compared to the control group in the second week, while this difference was maintained at the one-month follow-up (This study had several limitations. The fact that neither participants nor care providers were blinded to the aims of the study was a threat. The small number of participants in combination with a short follow-up period was also a significant limitation of this research. Another limitation concerns the selection of the FTF test. This test is affected by a number of factors such as hamstring tightness or sacroiliac joint dysfunction, while it is limited to measure only the trunk bending movement without taking into account the rest of the movements. However, the FTF test was chosen because of its high reliability in people with low back pain (ICC = 0.99), as well as its ease of use [ | PMC10384820 |
5. Conclusions | disability, pain | The application of an MT protocol with TECAR using a resistive special bracelet electrode seems to improve pain and disability further than conventional MT in individuals with CNSLBP. The positive effect seems to be due to the combination of mechanical and thermal effects offered simultaneously by the two therapeutic methods. Moreover, the MT + TECAR combination seems to improve local sensitivity in the lumbar region more effectively. However, the greatest effect was found in fluid-poor tissue areas (such as tendons, joints, and bones) and less so in muscles. Finally, the thermal effect of TECAR seems to be responsible for improving mobility in the lumbo-pelvic region. In most measures, the improved values between the participants who followed the MT protocol with TECAR and the other groups were maintained for one month after the end of the treatments. However, the short duration of the intervention only gives us some indications without allowing safe conclusions to be drawn. More long-term research in the future might be able to shed more light on the matter. | PMC10384820 | |
Author Contributions | D.L. | Conceptualization, K.K., P.I., D.L., G.K. and T.A.; methodology, I.P.C., G.K., D.L., P.I., A.F. and G.T.; software, I.P.C., D.L., N.-M.K., A.S. and T.A.; validation, I.P.C., D.L. and G.C.; formal analysis, I.P.C., K.K. and G.T.; investigation, G.K., K.K., A.F., S.R.N. and P.I.; resources, G.K., I.P.C., D.L., P.I., K.K., A.F. and G.C.; data curation, I.P.C., D.L. and P.I.; writing—original draft preparation, K.K., P.I., D.L., G.K., I.P.C., A.F., S.R.N., N.-M.K., A.S., G.C., G.T. and T.A.; writing—review and editing, T.A., G.K. and P.I.; visualization, G.K. and I.P.C.; supervision, T.A.; project administration, T.A.; funding acquisition, T.A. All authors have read and agreed to the published version of the manuscript. | PMC10384820 | |
Institutional Review Board Statement | The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the Department of Physiotherapy of the International Hellenic University (No. EC-06/2022). | PMC10384820 | ||
Informed Consent Statement | Informed consent was obtained from all subjects involved in the study. | PMC10384820 | ||
Data Availability Statement | The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request. | PMC10384820 | ||
Conflicts of Interest | The authors declare no conflict of interest. | PMC10384820 | ||
References | MT protocol with TECAR: (CONSORT flow diagram of the study.Demographic characteristics of the three groups.MT = manual therapy; MT + TECAR = manual therapy plus TECAR.The mean (SD) values of the outcome measures for each time point for the three groups. The “Group” × “Time” interaction Between-group comparison: a = Group 1 vs. Group 2; b = Group 1 vs. Group 3; c = Group 2 vs. Group 3. * Between-group significant comparisons in the post hoc testing. | PMC10384820 | ||
1. Introduction | infection | CORONAVIRUS, INFECTION, CORONAVIRUS DISEASE 2019, SEVERE ACUTE RESPIRATORY SYNDROME | These authors contributed equally to this work.Despite the effectiveness and safety of COVID-19 vaccines, vaccine-induced responses decline over time; thus, booster vaccines have been approved globally. In addition, interest in natural compounds capable of improving host immunity has increased. This study aimed to examine the effect of Korean Red Ginseng (KRG) on virus-specific antibodies after COVID-19 vaccination. We conducted a 24 week clinical pilot study of 350 healthy subjects who received two doses of the COVID-19 vaccine and a booster vaccination (third dose). These subjects were randomized 1:2 to the KRG and control groups. We evaluated antibody response five times: just before the second dose (baseline), 2 weeks, 4 weeks, 12 weeks after the second dose, and 4 weeks after the third dose. The primary endpoints were changes in COVID-19 spike antibody titers and neutralizing antibody titers. The antibody formation rate of the KRG group was sustained higher than that of the control group for 12 weeks after the second dose. This trend was prominently observed in those above 50 years old. We found that KRG can help to increase and maintain vaccine response, highlighting that KRG could potentially be used as an immunomodulator with COVID-19 vaccines.Coronavirus disease 2019 (COVID-19), which is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused significant morbidity and mortality worldwide and an ongoing global public health crisis [Recent studies have suggested that the effectiveness of COVID-19 boosters also tends to dwindle over time, with waning occurring 5–9 weeks after a booster vaccination [Korean Red Ginseng (KRG), derived from However, no study has examined whether KRG affects COVID-19 vaccine-induced immune response and protection. Therefore, this study aimed to investigate the effect of KRG on the humoral response of hosts who received two doses of COVID-19 vaccines and a booster vaccination (third dose) in Korea. | PMC10097014 |
2. Materials and Methods | PMC10097014 | |||
2.1. Study Design and Participants | This longitudinal study evaluated KRG intake’s effect on COVID-19 antibodies after vaccination in Korean adults (Clinical Research Information Service, KCT0007342). The study was approved by the Institutional Review Board of Yongin Severance Hospital (IRB no. 9-2021-0101) and was conducted in compliance with the Declaration of Helsinki. Written informed consent was provided by all patients prior to participation. Sample size was calculated based on the following assumptions: the effect size (cohen’s d) 0.25, type I error of 0.05, power of 80%, and 1:2 ratio (KRG/control ratio). The number of subjects to be enrolled was determined to be 190 for the KRG group and 380 for the control group. The originally intended total sample size was 570, but the required number of enrollments was not achieved within the given study period. The KRG dose used in this study was 3 g of KRG tablet/day, containing ginsenoside, Rb1 (8.03 mg/g), Rb2 (2.80 mg/g), Rg3 (2.50 mg/g), Rg1 (1.18 mg/g), Rc (3.29 mg/g), Rf (1.47 mg/g), Re (1.29 mg/g), and Rd (1.0 mg/g). The KRG tablets were made by dehydrating extracts of KRG. A total of 534 subjects who received a COVID-19 vaccine were recruited in August 2021 and continued with follow up. Subjects were assigned to two groups: the KRG group was taking KRG continuously before the study KRG per day for four weeks from enrollment, and the control group did not take KRG. In total, 174 subjects were included in the KRG group and 331 in the control group. Because of incomplete follow up or refusal of a third dose of COVID-19 vaccine administration, 155 subjects were excluded. Thus, there were 149 subjects in the KRG group and 201 in the control group. All subjects completed five visits ( | PMC10097014 | ||
2.2. Study Outcomes | diabetes, psychiatric, angina, cardiovascular diseases | MALIGNANT TUMORS, DIABETES, MYOCARDIAL INFARCTION, STROKE, CARDIOVASCULAR DISEASES | The inclusion criteria for this study included the following: adults aged 30 years or older, participants who had taken red ginseng for at least one month within the last month prior to vaccination (KRG group), and individuals who had not taken red ginseng for two or more months before vaccination (control group). Subjects were excluded if they met any of the following criteria: patients being treated for cardiovascular diseases such as angina, myocardial infarction, stroke, uncontrolled diabetes, undergoing treatment for malignant tumors, taking antidepressants, antipsychotics, other psychiatric medications, and consuming functional foods including multivitamins. All subjects received the COVID-19 vaccine three times, and they visited the hospital five times to measure vaccine-induced antibodies to the spike protein receptor-binding domain (anti-S-Ab) and nucleocapsid (anti-NC) SARS-CoV-2 protein and anti-N-Ab. We checked anti-NC antibodies to evaluate whether patients were infected with COVID-19. No anti-NC antibodies were detected during or after vaccination. The second dose of the vaccine was administered four weeks after the first dose. We evaluated antibodies just before the second dose (baseline), 2, 4, and 12 weeks after the second dose, and 4 weeks after the third dose, independent of the type of vaccine. We first measured serum antibody levels and investigated possible changes at each time point. The change after 4 weeks compared with baseline was considered as the primary endpoint to calculate statistical power. We further compared changes in antibody levels in the KRG group vs. the control group. | PMC10097014 |
2.3. Measurement of Anthropometric and Biochemical Parameters | hypertension, diabetes | DIABETES, HYPERTENSION, -20 | Participants underwent five examinations: at baseline; 2, 4, and 12 weeks after their second COVID-19 vaccination, and 4 weeks after their third vaccination. At each visit, body weight, height, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were recorded. Height and weight were obtained with subjects wearing light indoor clothing without shoes to the nearest 0.1 cm (Seca 225, Hamburg, Germany) and 0.1 kg, respectively (GL-6000-20, Gyeonggi, Republic of Korea). SBP and DBP values were measured three times in a seated position after a 5 min rest using a standard mercury sphygmomanometer (Baumanometer, Gresham, OR, USA). At baseline, we measured cholesterol metabolites and surveyed smoking status and alcohol consumption. Subjects were categorized into non-smoker and current smoker groups. Current drinkers were defined as those who drank alcohol more than once a month. We adopted binary variables of presence or absence for a history of hypertension and diabetes on a self-reported questionnaire. Body mass index (BMI) was calculated as the ratio of weight (kg)/height (m | PMC10097014 |
2.4. Detection of Virus-Specific Antibodies | VIRUS | Automated ECLIA tests were performed with two types of SARS-CoV-2 antibody kits using the Cobas 8000 e801 module (Roche Diagnostics). The Elecsys Anti-SARS-CoV-2 assay (Roche Diagnostics) uses a recombinant protein representing the nucleocapsid (NC) antigen for the qualitative detection of antibodies against SARS-CoV-2. Results with <1.0 cut-off indexes (COI) were interpreted as negative for anti-NC antibodies, and those with ≥1.0 were interpreted as positive for anti-NC antibodies. The Elecsys Anti-SARS-CoV-2 S assay (Roche Diagnostics) uses a recombinant protein representing the spike protein receptor-binding domain to quantitatively determine antibodies against SARS-CoV-2. Results with <0.80 U/mL were interpreted as negative for anti-S-Ab, and those ≥0.80 U/mL were interpreted as positive for anti-S-Ab. The surrogated virus neutralization tests (sVNT) were performed with a cPass SARS-CoV-2 Neutralization Antibody Detection kit (GenScript, Piscataway, NJ, USA) using the SpectraMax 190 (Molecular Devices, San Jose, CA, USA) based on ELISA to detect anti-N-Ab against SARS-CoV-2. The results were interpreted as percentage inhibition (%inhibition) based on OD450 intensity. The manufacturer-recommended cut-off of ≥30% signal reduction was used to indicate the presence of anti-N-Ab. All percent inhibition results were converted to IU/mL of the WHO International Standard using an Excel-based conversion tool [ | PMC10097014 | |
2.5. Statistical Analysis | Data are shown as the means ± standard deviations for continuous variables and frequency (percentage) for categorical variables. Statistical significance for differences in baseline characteristics between the KRG and control groups was analyzed using independent Longitudinal antibody data were analyzed using the linear trapezoidal rule to compare anti-N-Ab in KRG and control groups because different subjects were assessed at different times from vaccination. [ | PMC10097014 | ||
3. Results | A total of 350 subjects who received three COVID-19 vaccines participated in this study. Subjects were allocated to the KRG group (Pearson’s correlation analysis was used to evaluate the association of anti-N-Ab and other covariates four weeks after the first dose (baseline). Age and vitamin D level were inversely correlated with anti-N-Ab (Age: r = −0.279, Common patterns of antibody response are shown in AUCs using a linear trapezoidal rule revealed statistically significant differences between the two groups for changes in anti-N-Ab over time. | PMC10097014 | ||
4. Discussion | PROLIFERATION, INFLAMMATION | In this study, vaccine-induced humoral responses in both the KRG and control groups significantly increased two weeks after the second administration of all vaccines; then, a decrease was observed until 12 weeks or just before booster vaccination. However, after booster vaccination, humoral responses increased again; this trend was similar to the data in previous studies [Poor vaccine responses, such as reduced humoral responses and delayed T-cell responses after vaccination, including COVID-19 vaccines, in the elderly due to immunosenescence are well established [There are several possible factors related to this unique outcome regarding the maintenance of a higher vaccine-induced humoral response in the KRG group. First, KRG can help to enhance the effectiveness of COVID-19 vaccines through cytokine and chemokine regulation and immune cell proliferation and activity increase. Chemokines and cytokines are critical factors in innate immunity and inflammation, and they play essential roles in developing and maintaining adaptive immunity in response to vaccination [COVID-19 vaccination also induces SARS-CoV-2-specific CD8+ and CD4+ T cell responses, which might confer long-term immune memory against SARS-CoV-2 [We further examined the effect of the micronutrients in KRG. Previous studies showed that the host’s nutritional status influences immune response, and recent comprehensive review papers demonstrated the importance of individual micronutrients for immune response and the various mechanisms of action [Conversely, Chillon et al. [This study has several limitations. First, the participants in the KRG group were those who took KRG per day for four weeks or were taking KRG continuously. For those taking KRG continuously, it was difficult to determine the dosage of KRG accurately. However, continuous KRG intake was checked at each visit through a questionnaire. The KRG group maintained a relatively high vaccine-induced immune response compared with the control group at the end of this study, suggesting that KRG provides sufficient vaccine benefits at an indirect level. Second, during the clinical trial period, to minimize the effects of nutrients other than KRG, we told participants to stop all nutritional supplements, including vitamin D, which could affect vaccine-induced immune responses. Although nutritional supplement intake was checked through a questionnaire at each visit, the possibility of unobserved bias could not be excluded because it was a self-reported questionnaire. Third, vaccines based on different immunogenicity principles were included, including mRNA-based vaccines (Pfizer and Moderna) and recombinant adenoviral vector vaccines (AstraZeneca). However, this study was not a randomized clinical trial comparing antibody titers and KRG intake between vaccines. Regardless of KRG intake, the overall vaccine effectiveness of our study was confirmed to be consistent with the results of the previous studies, in which the antibody titers peaked two weeks after the second vaccination and then decreased after that [Moreover, the study population could not choose a vaccine and were given vaccines according to the vaccine protocols defined by the Korean government (KDCC). This study was performed in a single center; however, our study had the benefit of observing the same subjects longitudinally. Last, the effect of KRG on cellular immunity after COVID-19 vaccination was not tested; however, KRG modulated or enhanced immune response in previous in vitro and in vivo studies [ | PMC10097014 | |
5. Conclusions | The protection against COVID-19 tends to decline over time after vaccination. This study showed the potential of KRG for boosting immunity and helping maintain a higher vaccine-induced humoral response after COVID-19 vaccination. Further studies will be needed to explain the mechanisms of these relationships in detail. | PMC10097014 | ||
Author Contributions | Conceptualization, J.Y., B.P., H.K., S.C. and D.J.; methodology, S.C. and H.K.; formal analysis, D.J.; investigation, J.Y., B.P., H.K., S.C. and D.J.; data curation, D.J.; writing—original draft preparation, J.Y., S.C. and D.J.; writing—review and editing, J.Y. and D.J.; supervision, D.J. All authors have read and agreed to the published version of the manuscript. | PMC10097014 | ||
Institutional Review Board Statement | The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Yongin Severance Hospital (IRB No. 9-2021-0101). | PMC10097014 | ||
Informed Consent Statement | Informed consent was obtained from all subjects involved in the study. | PMC10097014 | ||
Data Availability Statement | All data generated or analyzed during this study are available from the corresponding author upon proper request. | PMC10097014 | ||
Conflicts of Interest | The authors declare no conflict of interest. | PMC10097014 | ||
Abstract | PMC9854322 | |||
Background | cancer | CANCER | Health literacy plays an essential role in how individuals process health information to make decisions about health behaviours including cancer screening. Research is scarce to address health literacy as a strategy to improve cancer screening participation among women living with human immunodeficiency virus (HIV), particularly Black women who, despite the heavy burden of cervical cancer, report consistently low screening rates. | PMC9854322 |
Aim | CERVICAL CANCER | To assess the feasibility, acceptability and preliminary efficacy of a health literacy‐focused intervention called CHECC‐uP—Community‐based, HEalth literacy focused intervention for Cervical Cancer control—among women living with HIV. | PMC9854322 | |
Methods | CERVICAL CANCER | We conducted a community‐based, single‐blinded randomized pilot trial. A total of 123 eligible women were enrolled and randomized to one of two conditions, control (i.e., cervical cancer brochure) or intervention (cervical cancer brochure plus 30–60 min health literacy‐focused education followed by monthly phone counselling and navigation assistance for 6 months). Study assessments were done at baseline, 3 and 6 months. The final analysis sample included 58 women who completed all data points and whose Papanicolaou (Pap) test status was confirmed by medical records. | PMC9854322 | |
Results | All intervention participants who completed the programme would recommend the CHECC‐uP to other women living with HIV. However, adherence in the experimental conditions was low (49.6% attrition rate including 20 women who dropped out before the intervention began) due, in large part, to phone disconnection. Those who had received the intervention had a significantly higher Pap test rate compared to women in the control group at 6 months (50% vs. 21.9%, | PMC9854322 | ||
Conclusions | The CHECC‐uP was highly acceptable and led to improved Pap testing rates among Black women living with HIV. Future research should consider addressing social determinants of health such as phone connectivity as part of designing a retention plan targeting low‐income Black women living with HIV. | PMC9854322 | ||
Implications | The findings should be incorporated into a future intervention framework to fulfil the unmet needs of Black women living with HIV to facilitate their decision‐making about Pap test screening. | PMC9854322 | ||
Patient or Public Contribution | CERVICAL CANCER | Nineteen community members including women living with HIV along with HIV advocates and care providers participated in four focus groups to develop cervical cancer screening decision‐relevant information and the health literacy intervention. Additionally, a community advisory board was involved to provide guidance in the general design and conduct of the study.
Kyra J. W. Mendez completed this research during the PhD program at The Johns Hopkins University, School of Nursing. | PMC9854322 | |
INTRODUCTION | cancer | CANCER, VIRUS, CERVICAL CANCER, CERVICAL CANCER | Despite considerable progress in US cancer control over the past decades, certain groups continue to experience significant health disparities. Women living with human immunodeficiency virus (HIV) (WLH) experience a disproportionate cervical cancer burden because of an impaired immune response to the human papillomavirus, the virus that causes cervical cancer.Health literacy—‘the degree to which individuals have the capacity to obtain, process, and understand basic health information and services to make appropriate health decisions’ (para. 1)—is a key social determinant of health and is recognized as an essential element of access to high‐quality, patient‐centred care.Systematic reviews and meta‐analysesThe current study was designed to address this gap by testing a health literacy‐focused intervention programme called CHECC‐uP—Community‐based, HEalth literacy focused intervention for Cervical Cancer control among WLH. We conducted a pilot study with 3‐ and 6‐month follow‐ups to evaluate the feasibility, acceptability and preliminary efficacy of this intervention. We hypothesized that participation in the CHECC‐uP intervention would be associated with an increase in Pap testing and improvements in psychosocial outcomes. | PMC9854322 |
METHODS | PMC9854322 | |||
Design and sample | HIV | We used a community‐based, randomized controlled trial design to pilot test the CHECC‐uP intervention compared to an educational control (Clinical Trials Registry NCT03033888). Women were recruited from inner‐city HIV clinics, community organizations serving people with HIV or a university‐based HIV/AIDS research centre in Baltimore, MD, by posting study flyers in these organizations or advertising the study through social media (e.g., Facebook, Craigslist) and attending health fairs.A total of 123 eligible women completed the study assessment at baseline and were randomized (intervention, CONSORT | PMC9854322 | |
Randomization and intervention | HIV, human immunodeficiency virus | CERVICAL CANCER | We used computer‐generated random numbers to randomize women to either the intervention or control arm. The control arm received an educational brochure related to cervical cancer among WLH created for the purpose of the study. Women in the intervention arm received the educational brochure plus the study intervention, which consisted of health literacy education and phone counselling with navigation assistance. Specifically, a trained community health worker delivered health literacy education at a community centre conveniently located near a subway station in the central downtown area. The health literacy education (Table Main educational topics with examples of medical terminologies and role‐play contentsAbbreviations: HIV, human immunodeficiency virus; Pap, Papanicolaou.Development of our intervention to include health literacy as its core component was guided by the Precede‐Proceed model,At the end of the health literacy‐focused education session, women in the intervention group received a copy of the picture guidebook to reinforce what they had learned and practised in class. The follow‐up portion of the study intervention included monthly phone counselling for up to 6 months. Using a checklist addressing key talking points, the objectives of the follow‐up were to (1) reinforce health literacy knowledge and skills learned and practised from the education session; (2) address any questions or concerns the participant might have and (3) provide tailored navigation assistance with individually identified barriers to Pap test screening over a 6‐month period. | PMC9854322 |
Procedures | CERVICAL CANCER | The Johns Hopkins Institutional Review Board approved the study protocol. Once eligible women were identified, trained research assistants scheduled a visit to obtain written informed consent and collect baseline data at several community sites (e.g., nurse‐run community health centres or community organizations serving people with HIV). Upon completion of the baseline assessment, a trained community health worker delivered health literacy education to women assigned to the intervention arm.Initially, education sessions were scheduled for groups of six to eight women. However, the group‐based format presented substantial scheduling challenges to the study team with high rates of no‐shows. This led to the study team's decision to adopt individual education delivery. The education sessions lasted about 30 min, when offered individually, and 45–60 min, when offered as a group due to discussion during the group session. Within 1–2 weeks after completing education, intervention participants received monthly phone counselling sessions for 6 months. During each phone call, a counsellor checked the participant's progress toward completing a Pap test and answered questions or concerns about Pap test screening.For both intervention and control arms, we provided a copy of the Pap test brochure tailored to WLH, highlighting causes and symptoms of cervical cancer, risk factors for cervical cancer among WLH, the value of Pap screening and how to prepare for a Pap test. All of our educational materials were written at a sixth grade level or lower, as assessed by Flesch‐Kincaid grade‐level statistics in Microsoft Word. Additionally, all women in the study received a list of local community resources where a Pap test could be obtained free, or at a reduced cost, based on a sliding scale.Trained study staff who were blinded to the group assignment collected data at baseline, 3 and 6 months from the start of the intervention. After 6 months, intervention women were invited to postintervention qualitative interviews to share their experiences with CHECC‐uP. Every woman provided informed written consent. Enrolled participants received $20 at baseline and 3 months and $40 at 6 months for their time. Postintervention interview participants received an additional $30. | PMC9854322 | |
Measures | Depressive, cancer, PHQ‐9, depressive, depression, breast and cervical cancer, Cancer | CANCER, RECRUITMENT, CERVICAL CANCER, CERVICAL CANCER, CANCER | A study questionnaire was used to collect participants sociodemographic and medical characteristics. Data regarding Pap test status were assessed via medical record review. We used several study instruments to assess changes in WLH's psychosocial outcomes: Health literacy, cancer knowledge, self‐efficacy, cultural beliefs/attitudes and depression. We include the internal consistency for each instrument, which was calculated using the full sample (To assess health literacy, we used familiarity, navigation and numeracy subscales from the Assessment of Health Literacy in Cancer Screening (AHL‐C), a validated comprehensive health literacy instrument with Cancer knowledge was measured by the Cervical Cancer Knowledge (CCK) Test which consists of 10 items (Self‐efficacy related to cervical cancer screening was assessed by the Cervical Cancer Self‐Efficacy scale.Cultural beliefs and attitudes were assessed using a modified nine‐item inventory (5‐point Likert; 1 = strongly disagree to 5 = strongly agree), which was adopted from the cultural barriers to breast and cervical cancer screening questionnaire.Depressive symptoms were measured using the Patient Health Questionnaire‐9 (PHQ‐9). PHQ‐9 is a well‐validated and widely disseminated screener for depressive symptoms.We also collected data on the feasibility and acceptability of the CHECC‐uP. The feasibility of the study was examined using multiple sources of data, such as study recruitment and retention, attendance at education sessions and follow‐up phone counselling completion rates. Acceptability was assessed using a questionnaire developed for the purpose of this study. The survey included self‐reported satisfaction with the intervention programme, as well as the receipt (e.g., reading the intervention material), helpfulness and application (e.g., applied contents from the material to get a Pap test) of intervention materials. | PMC9854322 |
Statistical analyses | Analysis was performed using data from the 58 participants who completed all data points and whose Pap test status was confirmed objectively by medical records (Figure | PMC9854322 |
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