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Ethics approval and consent to participate | DER | The study complies with the principles laid down in the Declaration of Helsinki and has been approved by the ethics committee of the Medical Association Berlin (Berlin—Ethik-Kommission der Ärztekammer Berlin). The reference number is Eth-27/10, it has been retrospectively registered at the WHO-approved registry German Registry for Clinical Trials (Deutsches Register Klinischer Studien, DRKS), trial registration number DRKS00013335 on 27/11/2017. Written informed consent has been obtained from all patients prior to study enrollment. | PMC9990362 | |
Consent for publication | Approved for submission by all the named authors. | PMC9990362 | ||
Competing interests | FS reports grants from Helixor Heilmittel GmbH (travel costs and honoraria for speaking), grants from AstraZeneca (travel costs and honoraria for speaking), grants from Abnoba GmbH, and grants from Iscador AG, outside the submitted work. DS reports grants from the foundations Rut und Klaus Bahlsen Stiftung and the Förderstiftung MHH plus outside the submitted work. CG reports grants from Iscador AG, outside the submitted work. The other authors have declared that no competing interests exist. No payment was received for any other aspects of the submitted work. There are no patents, products in development or marketed products to declare. There are no other relationships/conditions/circumstances that present a potential competing interests. | PMC9990362 | ||
References | PMC9990362 | |||
Background | nonobstructive coronary arteries | MYOCARDIAL INFARCTION (MI) | The pathobiology of myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) is often uncertain. Investigating biomarker concentrations and their changes may offer novel pathophysiological insights. | PMC9973579 |
Methods and Results | obstructive (stenosis, obstructive coronary artery disease | REGRESSION, CORONARY ARTERY DISEASE | In this post hoc study of the PLATO (Platelet Inhibition and Patient Outcomes) trial, concentrations of hs‐cTnT (high‐sensitivity cardiac troponin T), NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), hs‐CRP (high‐sensitivity C‐reactive protein), and GDF‐15 (growth differentiation factor 15) were measured in patients with MINOCA at baseline (n=554) and at 1‐month follow‐up (n=107). For comparisons, biomarkers were also measured in patients with MI with obstructive (stenosis ≥50%) coronary artery disease (baseline: n=11 106; follow‐up: n=2755]). Adjusted linear regression models were used to compare concentrations and their short‐ and long‐term changes. The adjusted geometric mean ratios (GMRs) in patients with MINOCA (median age, 61 years; 50.4% women) indicated lower hs‐cTnT (GMR, 0.77 [95% CI, 0.68–0.88]) but higher hs‐CRP (GMR, 1.21 [95% CI, 1.08–1.37]) and GDF‐15 concentrations (GMR, 1.06 [95% CI, 1.02–1.11]) at baseline compared with patients with MI with obstructive coronary artery disease, whereas NT‐proBNP concentrations were similar. Temporal decreases in hs‐cTnT, NT‐proBNP, and hs‐CRP concentrations until 1‐month follow‐up were more pronounced in patients with MINOCA. At follow‐up, patients with MINOCA had lower concentrations of hs‐cTnT (GMR, 0.71 [95% CI, 0.60–0.84]), NT‐proBNP (GMR, 0.45 [95% CI, 0.36–0.56]), and hs‐CRP (GMR, 0.68 [95% CI, 0.53–0.86]). One‐month GDF‐15 concentrations were similar between both groups with MI. | PMC9973579 |
Conclusions | myocardial injury, obstructive coronary artery disease | MYOCARDIAL DYSFUNCTION | Biomarker concentrations suggest greater initial inflammatory activity, similar degree of myocardial dysfunction, and less pronounced myocardial injury during the acute phase of MINOCA compared with MI with obstructive coronary artery disease but also faster myocardial recovery. | PMC9973579 |
Registration | URL: | PMC9973579 | ||
Subject Categories | Supplemental Material is available at For Sources of Funding and Disclosures, see page 13.*The PLATO Trial Investigators are listed in the supplement. | PMC9973579 | ||
Nonstandard Abbreviations and Acronyms | nonobstructive coronary, arteriesPlatelet, Myocardial Infarction | MYOCARDIAL INFARCTION, MYOCARDIAL INFARCTION | growth differentiation factor 15geometric mean ratiohigh‐sensitivity cardiac troponin Tmyocardial infarction with nonobstructive coronary arteriesPlatelet Inhibition and Patient OutcomesStockholm Myocardial Infarction With Normal Coronaries
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Clinical Perspective | PMC9973579 | |||
What Is New? | myocardial damage, nonobstructive coronary arteries, obstructive coronary artery disease, inflammation, myocardial affection | MYOCARDIAL DYSFUNCTION, INFLAMMATION, MYOCARDIAL INFARCTION (MI) |
The present study is the first to examine temporal changes in established biomarkers of inflammation and myocardial damage/dysfunction in myocardial infarction (MI) with nonobstructive coronary arteries.Biomarkers indicate differences in pathobiology between patients with MI with nonobstructive coronary arteries and MI with obstructive coronary artery disease, with greater initial inflammatory activity, similar degree of myocardial dysfunction, and less pronounced myocardial damage during the acute phase of MINOCA.Also, there were a more transient myocardial affection and faster recovery in patients with MINOCA compared with MI‐CAD. | PMC9973579 |
What Are the Clinical Implications? | myocardial damage, inflammation, hypoxia, nonobstructive coronary arteries | INFLAMMATION, HYPOXIA, PATHOPHYSIOLOGY, MYOCARDIAL DYSFUNCTION, OXIDATIVE STRESS |
Our results aid in understanding the pathophysiology of MI with nonobstructive coronary arteries and highlight processes that may be further explored on patient management.Around 5% to 10%Studies investigating the mechanisms behind MINOCA have relied on assessment of clinical risk factors, noninvasive myocardial imaging, and invasive coronary visualization and functional testing.The aim of the present analysis was to explore concentrations and changes of biomarkers of myocardial damage (hs‐cTnT [high‐sensitivity cardiac troponin T]), myocardial dysfunction (NT‐proBNP [N‐terminal pro‐B‐type natriuretic peptide]), inflammation (hs‐CRP [high‐sensitivity C‐reactive protein], GDF‐15 [growth differentiation factor 15]), and oxidative stress and hypoxia (GDF‐15) | PMC9973579 |
METHODS | The data set analyzed in this study is not publicly available because of ethical restrictions. However, access can be made available at Uppsala Clinical Research Center (Uppsala, Sweden) upon reasonable request and under the provision that the data are accessed on site and do not leave Uppsala University. | PMC9973579 | ||
Study Population | This is an observational post hoc study of patients included in the PLATO (Platelet Inhibition and Patient Outcomes) trial ( | PMC9973579 | ||
Inclusion of patients into groups with MINOCA and MI‐CAD. | CAD, nonobstructive coronary arteries, obstructive coronary artery disease | CAD, MYOCARDIAL INFARCTION, CORONARY ARTERY DISEASE, ACUTE CORONARY SYNDROME | ACS indicates acute coronary syndrome; CAD, coronary artery disease; hs‐cTnT, high‐sensitivity cardiac troponin T; MI‐CAD, myocardial infarction with obstructive coronary artery disease; MINOCA, myocardial infarction with nonobstructive coronary arteries; and PLATO, Platelet Inhibition and Patient Outcomes.The PLATO trial and the current study were conducted in adherence with the Declaration of Helsinki and were approved by ethical review boards. All patients provided written informed consent to participate and received routine medical care with the exception of randomized treatment (ticagrelor or clopidogrel). | PMC9973579 |
Definitions | coronary stenosis, NSTEMI, obstructive coronary artery disease | CORONARY STENOSIS, STENOSES | The final diagnosis of MI together with the presence of ST‐segment–elevation MI (STEMI) or non–ST‐segment–elevation MI (NSTEMI) was determined at discharge by the investigators at each trial site. There was no formal adjudication of the index diagnoses. Patients were deemed to have MINOCA when diagnosed as MI but without a significant (ie, <50%) coronary stenosis in any vessel at coronary angiography and without coronary revascularization before or during the index hospitalization. The reason for excluding patients with prior revascularization from the cohort with MINOCA was to dismiss patients with previous manifest obstructive coronary artery disease. Patients with MI with a significant (ie, ≥50%) coronary stenosis at coronary angiography in at least 1 vessel were considered as having MI‐CAD. A small number of patients classified as having nonobstructive stenoses underwent coronary revascularization, although percutaneous coronary intervention of MINOCA lesions is not encouraged in the consensus documents on MINOCA of the European Society of Cardiology | PMC9973579 |
Biomarker Analysis | Plasma was collected by venous puncture at baseline (a median of 15.1 and 8.9 hours from onset of symptoms for patients with MINOCA and MI‐CAD, respectively) and after 1 month in a subset of paired patients and stored in aliquots in −70 °C until analysis. Baseline blood samples were obtained in all patients before coronary angiography. Biomarker concentrations were centrally measured at the Uppsala Clinical Research Center Laboratory (Uppsala, Sweden): hs‐cTnT, NT‐proBNP, and GDF‐15 were analyzed on Cobas Analytics Immunoanalyzers (Roche Diagnostics); and hs‐CRP was analyzed on the Architect platform (Abbott Diagnostics). All analyses were done according to the instructions of the assay manufacturers and have been described in detail previously. | PMC9973579 | ||
Statistical Analysis | diabetes, chronic kidney disease, dyslipidemia | ISCHEMIC STROKE, PERIPHERAL VASCULAR DISEASE, DYSLIPIDEMIA, REGRESSION, HEART FAILURE, HYPERTENSION, DIABETES | Categorical variables were reported as frequencies and percentages, and continuous variables were reported as medians with interquartile ranges. Distributions of biomarker concentrations were displayed in empirical cumulative distribution function plots.Differences in biomarker concentration distributions between MINOCA and MI‐CAD at baseline and at 1 month later were investigated using Mann‐Whitney tests. To study these differences adjusting for potential confounders, we performed linear regression analyses using ln‐transformed concentrations of hs‐cTnT, NT‐proBNP, hs‐CRP, and GDF‐15 as response variables. The concentrations are presented as geometric means and were calculated using the antilogs of the model‐adjusted means of the ln‐transformed data; thus, the comparisons between MINOCA and MI‐CAD are presented as adjusted geometric mean ratios. A geometric mean ratio >1 corresponds to a higher biomarker concentration in MINOCA, and a geometric mean ratio <1 corresponds to a higher biomarker concentration in MI‐CAD. The analyses were adjusted in 2 models. Model 1 was unadjusted at baseline, whereas at 1‐month follow‐up, it was adjusted for randomized treatment (clopidogrel versus ticagrelor) and corresponding biomarker concentration at baseline. Model 2 was additionally adjusted for baseline clinical characteristics (age, sex, body mass index, current smoking, hypertension, dyslipidemia [medical history or lipid treatment at admission], diabetes, chronic kidney disease [medical history], MI type [STEMI/NSTEMI], previous MI, previous ischemic stroke, previous heart failure, and peripheral vascular disease). Additional adjustment was made at baseline for hours from the onset of symptoms to blood sampling, and at 1‐month follow‐up for revascularization during index hospitalization. A further analysis was done with adjustment for medications at follow‐up (antiplatelets, P2YTo visualize temporal biomarker concentration changes in MINOCA and MI‐CAD during hospital stay, linear regression models including time from symptom onset, MINOCA/MI‐CAD classification, and MI type (STEMI/NSTEMI), as well as all pairwise interactions between the 3, were fitted. Time was modeled as a restricted cubic spline, with 4 knots placed at the 5th, 35th, 65th, and 95th sample percentiles, to allow for nonlinear associations (for details, see Data Differences between MINOCA and MI‐CAD in delta changes of biomarker concentrations from baseline to 1 month later were assessed using Mann‐Whitney tests.There were a few missing biomarker values that were not accounted for in the statistical analyses. In all tests, a statement of statistical significance implies a 2‐sided | PMC9973579 |
RESULTS | NSTEMI, nonobstructive coronary arteries, obstructive coronary artery disease | BLOOD, MYOCARDIAL INFARCTION | Biomarker results were available at baseline in 554 patients with MINOCA and 11 106 patients with MI‐CAD; at 1‐month follow‐up, biomarker results were available in 107 patients with MINOCA and 2755 patients with MI‐CAD (Figure Baseline Characteristics in Patients With MINOCA and MI‐CADData presented as numbers (with percentages) for categorical variables or medians (with interquartile ranges) for continuous variables. Information on clinical characteristics and in‐hospital revascularization was collected at the index hospitalization. Medications were considered at the time of blood sampling at baseline. BMI indicates body mass index; CABG, coronary artery bypass grafting; eGFR, estimated glomerular filtration rate; MI, myocardial infarction; MI‐CAD, MI with obstructive coronary artery disease; MINOCA, MI with nonobstructive coronary arteries; NSTEMI, non–ST‐segment–elevation MI; PCI, percutaneous coronary intervention; RAAS, renin‐angiotensin‐aldosterone system; and STEMI, ST‐segment–elevation MI.On the basis of medical history or lipid treatment at admission.On the basis of cystatin C. Missing: n=17 patients with MINOCA and n=300 patients with MI‐CAD in the baseline cohort; n=28 patients with MI‐CAD in the follow‐up cohort.Overall, the time from onset of symptoms to blood sampling at baseline was 15.1 (8.1–21.3) hours in patients with MINOCA and 8.9 (3.9–17.3) hours in those with MI‐CAD. Blood samples were collected closer to the onset of symptoms in patients with STEMI compared with NSTEMI, in both the MINOCA and the MI‐CAD groups (Table Time From Symptom Onset to Blood Sampling at Baseline in the Total Cohort and Concentrations of Biomarkers Stratified by MINOCA or MI‐CAD and STEMI or NSTEMIData presented as medians (with interquartile ranges). GDF‐15 indicates growth differentiation factor 15; hs‐CRP, high‐sensitivity C‐reactive protein; hs‐cTnT, high‐sensitivity cardiac troponin T; MI‐CAD, myocardial infarction with obstructive coronary artery disease; MINOCA, myocardial infarction with nonobstructive coronary arteries; NSTEMI, non–ST‐segment–elevation myocardial infarction; NT‐proBNP, N‐terminal pro‐B‐type natriuretic peptide; and STEMI, ST‐segment–elevation myocardial infarction. | PMC9973579 |
Adjusted spline models illustrating the association of mean biomarker concentrations with time in patients with MINOCA and MI‐CAD divided on STEMI or NSTEMI status. | PMC9973579 | |||
Biomarker Concentrations at Baseline and Short‐Term Changes | chronic kidney disease, nonobstructive coronary arteries, obstructive coronary artery disease, dyslipidemia, heart failure, diabetes | MYOCARDIAL INFARCTION, ISCHEMIC STROKE, PERIPHERAL VASCULAR DISEASE, DYSLIPIDEMIA, REGRESSION, HEART FAILURE, HYPERTENSION, DIABETES | Baseline concentrations of hs‐cTnT, NT‐proBNP, hs‐CRP, and GDF‐15 in the total cohort of patients with MINOCA and MI‐CAD are presented in Table Biomarker Concentrations and Multiple Linear Regression Results in the Total Cohort at BaselineInflammationOxidative stressHypoxiaBiomarker data presented as medians (with interquartile ranges). Model 1: unadjusted. Model 2: adjusted for baseline clinical characteristics (age, sex, body mass index, current smoking, hypertension, dyslipidemia [medical history and/or lipid treatment at admission], diabetes, chronic kidney disease [medical history], myocardial infarction [MI] type [ST‐segment–elevation MI/non–ST‐segment–elevation MI], previous MI, previous ischemic stroke, previous heart failure, peripheral vascular disease, and hours from the onset of symptoms to blood sampling). GDF‐15 indicates growth differentiation factor 15; hs‐CRP, high‐sensitivity C‐reactive protein; hs‐cTnT, high‐sensitivity cardiac troponin T; MI‐CAD, MI with obstructive coronary artery disease; MINOCA, MI with nonobstructive coronary arteries; and NT‐proBNP, N‐terminal pro‐B‐type natriuretic peptide.Statistically significant values.Crude hs‐cTnT concentrations were similar between patients with MINOCA and MI‐CAD (Table Patients with MINOCA had higher crude NT‐proBNP concentrations compared with those with MI‐CAD (Table hs‐CRP concentrations were higher in patients with MINOCA compared with MI‐CAD in both crude and adjusted analyses (Table The crude GDF‐15 concentrations were similar between patients with MINOCA and MI‐CAD (Table | PMC9973579 |
Biomarker Concentrations at 1‐Month Follow‐Up and Long‐Term Changes Over Time | chronic kidney disease, nonobstructive coronary arteries, obstructive coronary artery disease, dyslipidemia, heart failure, diabetes | MYOCARDIAL INFARCTION, ISCHEMIC STROKE, PERIPHERAL VASCULAR DISEASE, DYSLIPIDEMIA, REGRESSION, HEART FAILURE, HYPERTENSION, DIABETES | One‐month biomarker concentrations in the follow‐up cohort are given in Table Biomarker Concentrations and Multiple Linear Regression Results in the Follow‐Up Cohort at 1 Month After the MIInflammationOxidative stressHypoxiaBiomarker data presented as medians (with interquartile ranges). Model 1: adjusted for randomized treatment (clopidogrel vs ticagrelor) and corresponding biomarker concentration at baseline. Model 2: additionally adjusted for baseline clinical characteristics (age, sex, body mass index, current smoking, hypertension, dyslipidemia [medical history and/or lipid treatment at admission], diabetes, chronic kidney disease [medical history], MI type [ST‐segment–elevation MI/non–ST‐segment–elevation MI], previous MI, previous ischemic stroke, previous heart failure, peripheral vascular disease, and revascularization during index hospitalization). GDF‐15 indicates growth differentiation factor 15; hs‐CRP, high‐sensitivity C‐reactive protein; hs‐cTnT, high‐sensitivity cardiac troponin T; MI, myocardial infarction; MI‐CAD, MI with obstructive coronary artery disease; MINOCA, MI with nonobstructive coronary arteries; and NT‐proBNP, N‐terminal pro‐B‐type natriuretic peptide.Statistically significant values. | PMC9973579 |
Temporal changes in biomarker concentrations from baseline to 1 month later in the follow‐up cohort of patients with MINOCA and MI‐CAD. | PMC9973579 | |||
DISCUSSION | myocardial damage, inflammation, myocardial affection, myocardial injury | INFLAMMATION, DYSFUNCTION | This is the first study examining temporal changes in established biomarkers of inflammation and myocardial damage and dysfunction in patients with MINOCA compared with MI‐CAD. Biomarkers were measured in the acute phase of the index MI and 1 month later in a follow‐up cohort, and careful consideration was taken of variables that potentially influence biomarker concentrations and dynamics. Our results indicate differences in the pathobiology between the MI groups, with more pronounced initial inflammatory activity and smaller myocardial injury during the acute phase of MINOCA and a more transient myocardial affection and faster recovery compared with MI‐CAD. | PMC9973579 |
Differences in Biomarker Concentrations in the Acute Phase of | NSTEMI, myocardial injury | ADVERSE EVENTS, OTHER CARDIOVASCULAR DISEASE | In the acute phase, the adjusted linear model showed higher hs‐cTnT concentrations in patients with MI‐CAD compared with MINOCA, indicating a greater degree of myocardial injury in those with MI‐CAD. Indeed, numericallyNT‐proBNP concentrations in patients with MINOCA were similar to patients with MI‐CAD, except for patients with NSTEMI, in whom a more rapid decline was seen after the initial 10 to 20 hours. This corresponds with previous dataHs‐CRP concentrations were overall higher in patients with MINOCA compared with MI‐CAD. This may be attributable to a proinflammatory disposition in patients with MINOCA.GDF‐15 is a stress‐responsive member of the transforming growth factor‐β cytokine superfamily and is a well‐established marker of poor prognosis and future adverse events in patients with MI but also other cardiovascular disease.An interesting observation was that the duration from onset of symptoms to blood sampling was substantially longer for patients with MINOCA than for patients with MI‐CAD. This might depend on a longer delay for patients with MINOCA to seek medical attention or a slower response from caregivers. Such structural biases might also have been present in other studies investigating biomarker concentrations in mixed populations with MI (ie, not only consisting of patients with MINOCA or MI‐CAD but also, and more important, of patients with STEMI and NSTEMI). In the present study, patients with NSTEMI experienced a 2‐fold to 3‐fold longer time to blood sampling from the onset of symptoms. Moreover, bear in mind that patients with STEMI and NSTEMI, in addition to MINOCA and MI‐CAD, displayed rather different biomarker dynamics of hs‐cTnT, NT‐proBNP, and hs‐CRP during the first 50 hours. Accordingly, time from symptom debut to blood sampling, MINOCA/MI‐CAD status, and STEMI/NSTEMI status need to be considered when evaluating biomarker concentrations in patients with MI. Indeed, the importance of considering these 3 variables was further substantiated by the significant global tests of interaction in the spline models. | PMC9973579 |
Biomarker Concentrations at 1 Month After the Index | Myocardial Infarction, myocardial injury | MYOCARDIAL INFARCTION, DYSFUNCTION, ACUTE CORONARY SYNDROME | The notion of a more favorable pathophysiological response in patients with MINOCA compared with MI‐CAD was supported by 1‐month biomarker concentrations and their changes from the acute phase of MI. More pronounced decreases for hs‐cTnT, NT‐proBNP, and hs‐CRP were noted in patients with MINOCA. At 1‐month follow‐up, concentrations of these biomarkers were lower both numerically and following adjustment. Taken together, this suggests less remaining myocardial injury, dysfunction, and inflammation/remodeling in the stable phase after MINOCA. However, as noticed both in the present study and in previous studies, GDF‐15 concentrations remain fairly constant from the acute to stable phase after acute coronary syndrome,Biomarker concentrations in the stable phase after an episode of MINOCA have only been investigated in the SMINC (Stockholm Myocardial Infarction With Normal Coronaries) study, | PMC9973579 |
Strengths and Limitations | The present study has several strengths. First, the study population was obtained from the PLATO trial, a large randomized control trial in which patients were carefully included and monitored. Second, we studied an international cohort with MINOCA, because the PLATO trial included patients from 862 centers in 43 countriesThere are also some limitations to our study. First, the study cohort stems from a randomized control trial and, thus, probably represents a healthier subset of the general population with MI. | PMC9973579 | ||
CONCLUSIONS | myocardial damage | MYOCARDIAL DYSFUNCTION | The concentrations and temporal changes of hs‐cTnT, NT‐proBNP, hs‐CRP, and GDF‐15 at the index MI and 1 month later suggest differences in the pathobiology between MINOCA and MI‐CAD. Our data indicate greater initial inflammatory activity, similar degree of myocardial dysfunction, and less pronounced myocardial damage in patients with MINOCA compared with MI‐CAD but also more transient processes in patients with MINOCA. Further analyses are needed to explore the underlying pathophysiological processes and potential implications on patient management. | PMC9973579 |
Sources of Funding | The present study was supported by the Swedish Foundation for Strategic Research (RB13‐0197) and Swedish Association of Local Authorities and Regions. The PLATO (Platelet Inhibition and Patient Outcomes) trial and the biomarker analyses were sponsored by AstraZeneca. The authors are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the manuscript, and its final contents. | PMC9973579 | ||
Disclosures | Dr Giannitsis reports grants and personal fees from Roche Diagnostics and Daiichi Sankyo; personal fees from Bayer Vital, Boehringer Ingelheim, AstraZeneca, BRAHMS Deutschland, Novo Nordisk, Idorsia, Radiometer, and Mitsubishi Chemicals, outside the submitted work. Dr Budaj reports personal fees and nonfinancial support from AstraZeneca, during the conduct of the study; personal fees and nonfinancial support from Bristol Myers Squibb and Sanofi Aventis; personal fees from Eisai, Novartis, GlaxoSmithKline, and Amgen; personal fees and nonfinancial support from Bayer, outside the submitted work. Dr Katus reports personal fees from Bayer, AstraZeneca, and Daiichi, outside the submitted work. Dr Storey reports research grants and personal fees from AstraZeneca, Cytosorbents, GlyCardial Diagnostics, and Thromboserin; personal fees from Alnylam, Bayer, Bristol Myers Squibb/Pfizer, Chiesi, CSL Behring, HengRui, Idorsia, Intas Pharmaceuticals, Medscape, Novartis, PhaseBio, Portola, and Sanofi Aventis. Dr Cornel reports membership of advisory boards with Amgen and AstraZeneca. Dr Siegbahn reports institutional research grants from AstraZeneca, Boehringer Ingelheim, Bristol‐Myers Squibb/Pfizer, GlaxoSmithKline, and Roche Diagnostics, outside the submitted work. Dr Hjort, Dr Eggers, T. Ghukasyan Lakic, J. Lindbäck, Dr Becker, Dr Wallentin, and Dr Lindahl have nothing to declare. | PMC9973579 | ||
Supporting information | Data S1Table S1Figure S1–S2Click here for additional data file. | PMC9973579 | ||
Acknowledgments | We thank the patients who participated in the PLATO (Platelet Inhibition and Patient Outcomes) trial and the investigators for their efforts. All principal investigators are listed in the supplemental material. | PMC9973579 | ||
References | PMC9973579 | |||
1. Introduction | psychological distress, human mood | The rice endosperm protein (REP) hydrolysate containing the following rice endosperm protein derived oligopeptides QQFLPEGQSQSQK, LPEGQSQSQK, and pEQFLPEGQSQSQK (a Rice (REP accounting for approximately 5% of rice endosperm is not only nutritionally important but also shows various physiological functions such as anti-hyperglycemia, anti-hyperuricemia, and anti-obesity when orally administrated [Mental illness threatens many populations today. A great number of people are reported to suffer from psychological distress [Rice endosperm protein hydrolysate (REP hydrolysate) containing the following rice oligo peptides; QQFLPEGQSQSQK, LPEGQSQSQK, and pEQFLPEGQSQSQK (a Two clinical studies were designed: Study 1 for the single-dose effect of REP hydrolysate on human mood and Study 2 for the effect of the repeated intake of REP hydrolysate on human mood. The aim of this study was to evaluate the effects of REP hydrolysate consumption on human mood. | PMC10421398 | |
2. Materials and Methods | PMC10421398 | |||
2.1. Study Design | This study was performed with a randomized, double-blind, and placebo-controlled design. Study 1 and Study 2 were conducted to evaluate our hypothesis of whether the intake of rice endosperm protein hydrolysate improved the negative mood status of humans when consumed only once (Study 1) and once a day for 4 weeks (Study 2). | PMC10421398 | ||
2.1.1. Study 1 | Participants visited the study facility on the first test day. After a health check, the Profile of Mood Status 2nd edition for adults (POMS 2) [The animal study indicated that the positive effect of REP hydrolysate might be observed in a short time. Namely, the administration of REP hydrolysate shortened the immobile time on the tail suspension test by 5 min after a single oral administration. Furthermore, a previous clinical trial (Clinical Trial Registry No. UMIN 000041724) indicated that REP hydrolysate single intake induced a strong effect size of d = 0.8 in inter-group comparison on the Euthymia Scale change. Thus, Study 1 was designed to see whether a single intake of REP hydrolysate had an influence in humans. | PMC10421398 | ||
2.1.2. Study 2 | insomnia, Insomnia | EVENTS | Participants completed the POMS 2 and the Euthymia Scale on the third pre-examination day and completed the Insomnia Severity Index (ISI), which is a self-rating questionnaire to assess the subjective severity of insomnia, on the first day of the test food period as baseline evaluations. Participants answered the POMS 2, Euthymia Scale, and ISI once a week during the 4-week test food period. Within 3 days after the final day of the fourth week, participants visited the study facility for a health check and saliva sample collection. Life events were recorded throughout the entire study period.The study period was set to 4 weeks, because 4 weeks of repeated intake was hypothesized to be long enough to overcome the placebo effect and detect the intervention effect, as a clinical trial that investigated the effect of GABA on the subjective mood state showed the declined placebo effect on the fourth week in the 12 weeks of the trial period and showed significant intervention effect on the fourth week [ | PMC10421398 |
2.2. Procedure | All study procedures were reviewed and approved by the Ethics Committee of Medical Station Clinic (IRB no. 20000022, 8 July 2021) and were conducted in accordance with the criteria set by the declaration of Helsinki. The trial was preregistered at the UMIN Clinical Trial Registry (no. UMIN000045037). Throughout the entire period, this study was conducted according to a previously approved study protocol. This study was operated by EP Mediate Co., Ltd. (Tokyo, Japan) and performed at Iryo Hojin Shadan Kowa Clinic from August 2021 to March 2022. | PMC10421398 | ||
2.3. Participants | allergic, malignant tumor, Depression, allergic reactions, Fatigue | MALIGNANT TUMOR, REMISSION, ALLERGIC REACTION | Two hundred fifty-one potential participants were informed verbally and documentarily of this study and signed an informed consent form before participation. These candidates went through the following pre-examination sessions. In total, 76 subjects who were healthy and eligible to participate in this study based on the results of the pre-examinations participated in this clinical trial. The eligibility criteria were (1) those who were healthy adults 20–64 years of age and (2) those who scored higher than 50 on the Profile of Mood Status 2nd edition short form for adults (POMS 2) Fatigue–Inertia subscale and less than 50 on the POMS 2 Vigor–Activity subscale at least once in the two pre-examinations. Participants were excluded if they met the following exclusion criteria: (1) those who were under medical treatment due to mental health issues and/or tested positive on a Major Depression Episode Sheet, (2) those who were on night shift or whose lifestyle was day–night reversed, or who went to bed from 6:00 a.m. to 10:00 a.m. and woke up from 6:00 p.m. to 8:00 p.m. at least once per week, (3) those who habitually consumed energy drinks more than once a week, (4) those who saw a doctor, were under medical treatment, or who took medicines/supplements in order to reduce stress and/or improve sleep quality, (5) those who were allergic to or had shown allergic reactions to certain allergens, (6) those with a medical condition that required chronic drug administration or who had a history of malignant tumor that required drug administration except for those who were diagnosed as being in remission, (7) those whose hematology test and vital sign assessment results were categorized as worse than group D, as defined by the Japan Society of NINGEN Dock, (8) those who were currently attending another clinical trial, (9) those who planned to become pregnant or to breastfeed during the study period, and (10) those who the principal investigator decided were unable to undergo the investigations and/or observe the patient restrictions. Seventy-six participants who satisfied the criteria listed above were enrolled in this study and were randomly allocated to the REP hydrolysate arm ( | PMC10421398 |
2.4. Test Foods | The REP hydrolysate was manufactured by Kameda Seika Co., Ltd. (Niigata, Japan). A tablet type food containing REP hydrolysate (25 mg/each) was used as the active food for the REP hydrolysate group. Two tablets were administered per day. Participants were taught to take the daily dosage at once. The concentration of the active peptides or the rice oligo peptides, LPEGQSQSQK, QQFLPEGQSQSQK, and pEQFLPEGQSQSQK (a | PMC10421398 | ||
2.5. Measurements | PMC10421398 | |||
2.5.1. Subjective Mood State Questionnaire | TMD, euthymia, Anxiety, mood disturbance, Hostility, Anger, Depression, Confusion, Fatigue | The psychological status was assessed with the following validated questionnaires: the Profile of Mood Status 2nd edition short form for adults (POMS 2) and the Euthymia Scale. POMS 2 is a self-reported questionnaire that assesses mood. It has two categories: the negative mood state and the positive mood state. The negative mood state contains the following five subcategories: Anger–Hostility (AH), Confusion–Bewilderment (CB), Depression–Dejection (DD), Fatigue–Inertia (FI), and Tension–Anxiety (TA). The positive mood state contains Vigor–Activity (VA) and Friendliness (F). The total mood disturbance (TMD) was calculated for the individual participants by subtracting the score of the positive mood from the score of the negative mood. The reliability and validity of the Japanese version of the POMS 2 have been confirmed [The Euthymia Scale is a self-rated questionnaire for the self-assessment of euthymia. The reliability and validity of the Japanese version have recently been reported [ | PMC10421398 | |
2.5.2. Subjective Sleep Quality Evaluation | insomnia, Insomnia | The Insomnia Severity Index (ISI) is a questionnaire that measures the subjective severity of insomnia. A higher score indicates more severe insomnia. The reliability and validity of the Japanese version of the ISI were previously confirmed [ | PMC10421398 | |
2.5.3. Measurements of Salivary CgA Concentrations | CgA | SHIGA | Saliva was collected with a swab and centrifuge tubes. Collected saliva samples were stored at −80 °C until measurement. The concentration of the salivary Chromogranin A (CgA) was determined with a commercially available human CgA EIA kit (Yanaihara Institute Inc., Shizuoka, Japan). The total protein in the saliva samples was measured by the Bradford method with a commercially available dye-assay kit (Takara Bio Inc., Shiga, Japan). The concentration of CgA was corrected with the amount of salivary total protein. | PMC10421398 |
2.6. Outcomes | PMC10421398 | |||
2.6.1. Study 1 | SECONDARY | The primary outcome for study 1 was the POMS 2 scores (AH, CB, DD, FI, TA, VA, F, and TMD). The secondary outcome was the Euthymia Scale score and salivary CgA concentration. | PMC10421398 | |
2.6.2. Study 2 | SECONDARY | The primary endpoint was the change in the Euthymia Scale scores from the baseline to the fourth week of intervention. The secondary outcomes were the POMS 2 and ISI scores. | PMC10421398 | |
2.7. Sample Size Calculation | Based on the results of the previous clinical trial (Clinical Trial Registry no. UMIN 000041724), a total of 66 participants was calculated to be necessary to detect a difference of 1.27, with 1.7 standard deviations in the Euthymia Scale between the REP hydrolysate group and the placebo group with a two-sided significance level of 5% and 85% power. The final sample size was determined to be 76 with a predicted dropout rate of 15%. | PMC10421398 | ||
2.8. Randomization and Blinding | A person in charge of allocation randomly allocated the participants to the REP hydrolysate arm or the placebo arm with the block randomization method. A computationally generated random allocation sequence was used. The block size of the RCT was set to 4. The allocation factors were the POMS 2 score of the FI and VA and the total score of the Euthymia Scale. The person in charge of allocation concealed the allocation table until the day of allocation disclosure and ensured that the participants and the rest of the study members were appropriately blinded to the allocation. | PMC10421398 | ||
2.9. Statistical Analyses | The results are shown as the mean ± standard error of the mean (SEM). For Study 1, the changes before and after the intake of test food were evaluated. For Study 2, the changes from the baseline to the fourth week were evaluated. The independent | PMC10421398 | ||
3. Results | The participants’ enrollment in this study is described in | PMC10421398 | ||
3.1. Study 1 | PMC10421398 | |||
3.1.2. Salivary CgA Concentrations (Post Hoc) | CgA | As a subjective mood improvement was observed in Study 1, the salivary concentration of CgA was conducted as a post hoc analysis. CgA concentrations were evaluated in 66 of the 76 participants (placebo, | PMC10421398 | |
3.2. Study 2 | PMC10421398 | |||
4. Discussion | mental disorder, Anxiety, daytime disturbance | This study was conducted to confirm the effect of the single intake and repeated intake of REP hydrolysate on the subjective mood. The single intake of REP hydrolysate significantly improved the POMS 2 subscale of Tension–Anxiety (The single intake of REP hydrolysate showed a significant improvement in the POMS 2 Tension–Anxiety subscale (As a subjective mood improvement was observed in Study 1, the salivary concentration of the CgA was analyzed. The salivary CgA was selected because it reportedly reduces its concentration by anxiolytic ingredients, reflects acute psychological stress, has a relatively small daytime disturbance, and is rarely influenced by physical movement [The reason why no significant positive intervention effect of REP hydrolysate after the 4-week intake was observed might be because the duration of intervention was insufficient. As mentioned above, the animal study showed that the vagotomy treatment partially inhibited the effect of REP hydrolysate on the tail suspension test. This implies that the REP hydrolysate achieved an antidepressant-like effect through the humoral pathway, in addition to the neural pathway. For example, it is known that blood pressure is dually regulated by neural regulation and humoral regulation. Furthermore, it is controlled with neural regulation for the short term, whereas it is controlled with humoral regulation for the long term [Previous research reported that not only stressors in the past but also anticipating upcoming stressors can negatively affect the current status [Despite this study’s limitations, including the modest sample size, the POMS 2 validation confirmed only with younger population, the lack of information that could affect subjective mood states (e.g., past history of mental disorder and marriage status), the number of participants that were excluded from the salivary analysis, and no experiment-wide false detection rate evaluated, this study obtained positive results under the best conditions that could be achieved. | PMC10421398 | |
5. Conclusions | Anxiety, anxiety, nervousness | ADVERSE EFFECTS | In the present study, the 4-week intake of REP hydrolysate did not show a positive effect, possibly due to the insufficient length of intervention. The single intake of REP hydrolysate did not improve the Euthymia Scale or all of the subscales of POMS 2; yet, it showed a significant improvement in the POMS 2 Tension–Anxiety score and a significant reduction in the salivary CgA concentration without adverse effects. Hence, REP hydrolysate may be a helpful and harmless ingredient that can be used to relax anxiety symptoms and nervousness and prevent future related symptoms. | PMC10421398 |
Author Contributions | Conceptualization, R.N., A.I., K.U., Y.H. and H.T.; methodology, R.N., D.N. and Y.H.; data curation, R.N. and Y.H.; writing—original draft preparation, R.N.; writing—review and editing, D.N., M.S. and K.O.; visualization, R.N.; supervision, D.N.; project administration, H.T. and K.O.; funding acquisition, A.I. and K.O. All authors have read and agreed to the published version of the manuscript. | PMC10421398 | ||
Institutional Review Board Statement | This study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Medical Station Clinic (IRB no. 20000022, 8 July 2021). | PMC10421398 | ||
Informed Consent Statement | Informed consent was obtained from all subjects involved in the study. | PMC10421398 | ||
Data Availability Statement | Not applicable. | PMC10421398 | ||
Conflicts of Interest | R.N., Y.H., K.U., A.I. and H.T. are the employees of Kameda Seika Co., Ltd. or the study’s sponsor. The other authors declare no conflict of interest in association with the present study. | PMC10421398 | ||
References | Anxiety, Insomnia, Hostility, Anger, Depression, Confusion, Fatigue | Flow diagram for study participants’ eligibility, enrollment, and followup.Background characteristics of participants.POMS, Profile of Mood Status; FI, Fatigue–Inertia; VA, Vigor–Activity. Values for the POMS 2 and Euthymia Scale were measured at the third pre-examination point. Other values were measured at the first pre-examination point. The baseline score of the POMS2 and Euthymia Scale are shown as the mean ± SEM. The other baseline parameters are shown as the mean ± S.D. Overall study schedule.POMS, Profile of Mood Status; ISI, Insomnia Severity Index. Each measurement was performed on the days with circles (●). ISI at 0 week was conducted before the test food intake as the baseline of Study 2. The test food was consumed once a day over the 4-week study period (highlighted).Results of the POMS 2 in Study 1.Values were shown as the mean ± SEM. POMS, Profile of Mood Status; AH, Anger–Hostility; CB, Confusion–Bewilderment; DD, Depression–Dejection; FI, Fatigue–Inertia; TA, Tension–Anxiety; VA, Vigor–Activity; F, Friendliness; TMD, Total Mood Disturbance. Results of the Euthymia Scale in Study 1.Values are shown as the mean ± SEM. Salivary CgA concentrations in Study 1.Values are shown as the mean ± SEM. CgA; Chromogranin A. Results of the POMS 2 in Study 2.Values are shown as the mean ± SEM. POMS, Profile of Mood Status; AH, Anger–Hostility; CB, Confusion–Bewilderment; DD, Depression–Dejection; FI, Fatigue–Inertia; TA, Tension–Anxiety; VA, Vigor–Activity; F, Friendliness; TMD, Total Mood Disturbance. Results of the Euthymia Scale in Study 2.Values were shown as the mean ± SEM. Results of the ISI.Values were shown as the mean ± SEM. ISI, Insomnia Severity Index. | PMC10421398 | |
1. Introduction | Saudi, injuries | COMMUNICABLE DISEASES | Encouraging physical activity (PA) for adolescents is necessary to achieve and maintain optimal health, but it may increase the risk of PA-related injuries. This study sought to assess the frequency, location, type, and severity of PA-related injuries in Saudi students aged 13 to 18 years and to identify associated risk factors. A total of 402 students, including 206 boys aged 15.87 ± 1.69 years and 196 girls aged 15.83 ± 1.70 years, were randomly assigned to participate in this study. For each participant, height, weight, body mass index, and fat percentage were measured. Responses to a specially designed four-part self-administered questionnaire were also collected. Results revealed that better specific knowledge was associated with a lower likelihood of sustaining injuries (β = −0.136; Physical activity (PA) participation helps maintain and improve a person’s physical, social, and mental health at different stages of life, including increasing cardiorespiratory and muscular fitness, bone density, and reducing the risk of disabilities and communicable diseases [Studies have also indicated that children and adolescents need at least an hour of physical activity of varying intensity most days of the week to promote health and well-being [Estimating the rate of PA-related injuries is challenging [Merkel [In light of these observations, the development of a strategy aimed at reducing the risk of injuries, protecting individual health, and increasing physical and sports safety is a crucial element in reducing the reluctance of children and adolescents to engage in PA. Ensuring participation in PA contributes to the development of public health [The assessment of PA characteristics is one of the methods used to identify possible modifiable and intrinsic risk factors for PA-related injuries. Several studies have shown a close relationship between the various components of physical fitness and risk factors associated with PA-related injuries [According to Truong et al. [Epidemiological studies have shown that injured athletes value healthcare professionals who engage and involve them in their care through strategies such as goal-setting. A strong therapeutic alliance in which the goals and values of each athlete are respected results in positive rehabilitation experiences and increased trust in providers. Open discussions with providers and coaches allowed athletes to make decisions about surgery, rehabilitation, or a return to sports, helping prevent injuries. Beidler et al. [Therefore, the present study aimed to assess the frequency of PA-related injuries among Saudi adolescents aged 13–18 to determine the location of the injury in the body area, the types of injuries, and whether the injury required urgent medical attention, and subsequently to investigate the association of these factors with gender, age, body mass index (BMI), knowledge of PA-related injuries, SB, and level of weekly physical activity. We hypothesized that boys reported more PA-related injuries than girls. We also hypothesized that participants with a good knowledge of PA-related injuries would be less likely to sustain PA-related injuries than participants with low knowledge. Additionally, it was hypothesized that participants with higher SB and reduced levels of PA were more likely to sustain PA-related injuries than those with lower SB and a higher level of PA. Finally, we hypothesized that lower limb bruises and strains were the most common PA-related injuries among Saudi boys, while upper limb strains were the most common PA-related injuries among girls. | PMC10001543 |
2. Methods | PMC10001543 | |||
2.1. Participants | disapproval, overweight | OBESE | According to the Saudi Ministry of Education—General Education Statistics at The positive responses received concerned 410 students (210 boys and 200 girls), while the others refused to participate. The disapproval was mainly attributed to cultural reasons that discourage participation in such studies. Before the measurements, students who met one or more criteria from the following list were excluded: age under 13 or over 18, disability, or any contraindication to PA. Failure of one or more of the study trials and lack of signed informed consent from participants aged 16 or older or parents younger than 16 were also considered exclusion criteria.After measurements, the results were checked for outliers with gender-specific Z-scores. As a general rule, values with a Z-score greater than 3 or less than −3 are often considered outliers and were excluded. A total of 8 outliers were determined and the final sample retained for analysis was 402 students (206 boys and 196 girls) aged 13 to 18. Participants were categorized into four BMI groups according to age- and sex-specific cutoffs suggested by the 2007 WHO Growth Reference (5–19 years): (1) underweight (UW; BMI-for-age < 5th percentile), normal weight (NW; 5th percentile ≤ BMI-for-age < 85th percentile), overweight (OW; 85th percentile ≤ BMI-for-age < 95th percentile), and obese (OB; BMI-for-age ≥ 95th percentile) (from de Onis et al. [ | PMC10001543 |
2.2. Procedures and Ethics | This study was conducted between September 2022 and November 2022 in accordance with the Declaration of Helsinki (rev. 2013) relating to the ethical principles for medical research involving human subjects [Prior to the measurements, participants and their parents were invited to a meeting with the research team to be informed about the purpose of the study and to understand the study protocol and possible effects that might result. An explanatory letter was also sent to all parents who were unable to attend the meeting and who were asked to complete an informed consent form for their children’s participation in the study. Once the ethical consents were signed, the height, weight, and body composition were measured for each participant, and at the same time, responses to a specially designed self-administered four-part questionnaire were collected (demographics, knowledge of PA-related injuries, PA levels, and SB). All measurements were performed in air-conditioned classrooms and all participants were instructed not to eat or drink two hours before the anthropometric measurements and to dry their feet thoroughly before walking on the measuring device. | PMC10001543 | ||
2.3. Measurements | PMC10001543 | |||
2.3.1. Anthropometric Parameters | For each participant, height was measured using a stadiometer (Holtain, Crymych, Wales, UK), and weight, BMI, and fat percentage were determined using bioelectrical impedance with a body composition monitor (Omron, Body Composition Monitor BF 508, Kyoto, Japan). | PMC10001543 | ||
2.3.2. Physical Activity-Related Injuries Parameters | COMPLICATIONS | Based on a questionnaire from the work of Wang and Huang [An acceptable PA-related injury must have met at least one of the following criteria: the student (1) must stop the current PA; (2) cannot participate in the next scheduled PA; (3) cannot go to class the next day; (4) should seek medical attention (including first aid, medical consultation, or physical therapy, but excluding those using only bandages) [Participant knowledge was assessed with 25 five-point Likert-scale questions concerning symptom recognition, complications, and general knowledge about PA-related injuries and their first aid. The correct answer for each question was identified and coded 1, while the wrong answer was coded 0. The total score for knowledge was determined by adding the scores of the 25 questions. Scores ranged from 1 to 25, meaning that the higher the score, the higher the knowledge. Using three percentiles (33) to determine knowledge of PA-related injuries, a score of 1 to 8 points indicates poor proficiency, a score of 9 to 16 points indicates intermediate proficiency, and a score of 17 or more points indicates good proficiency. | PMC10001543 | |
2.3.3. Parameters Related to Physical Activity | The assessment was conducted using the Arabic version of the Physical Activity Questionnaire for adolescents (PAQ-A) [To be easily understood by all participants, the English version of the PAQ-A has been translated and adapted to the Saudi context following the recommendations of Beaton et al. [ | PMC10001543 | ||
2.3.4. Parameters Related to Sedentary Behaviors | Evaluated using the NSW Schools Physical Activity and Nutrition Survey [ | PMC10001543 | ||
2.3.5. Reliability and Validity of PAQ-A | The exploratory factor and principal component analysis results indicate that the Kaiser–Meyer–Olkin measure of sampling adequacy was 0.697, which is above the acceptable 0.6 threshold. The Bartlett’s test sphericity score was statistically significant ( | PMC10001543 | ||
2.4. Statistical Analysis | The descriptive analysis of the sample and variables was conducted with the calculation of means, standard deviations, and frequencies. The normality of the distributions was tested using histograms and absolute values of skewness and kurtosis. An absolute skew value greater than 2 or an absolute kurtosis greater than 7 were used as reference values to determine substantial non-normality [ | PMC10001543 | ||
3. Results | PMC10001543 | |||
3.1. Sample Characteristics | injuries, fractures, fat-free mass | A total of 402 students completed all the parts of the study and were analyzed. Of these, 196 were girls (48.76%) aged 15.83 ± 1.7 years, and 206 were boys (51.24%) aged 15.87 ± 1.69 years. Referring to the sex-specific BMI-for-age percentile charts, the overall prevalence of overweight and obesity in boys was 11.7% and 29.1% and in girls 8.7% and 15.3%, respectively. Significant differences were noted in weight, height, BMI, PBF, and fat-free mass (Of the 402 individuals surveyed, 184 participants (45.77%; 118 males and 66 females) reported having suffered PA-related injuries in the past year, of which 93 subjects (55 males and 38 females) suffered one injury, 54 subjects (41 males and 13 females) suffered two injuries, and 37 subjects (22 males and 15 females) suffered three or more PA-related injuries. Bruises (29 cases) and strains (27 cases) were the most common types of PA-related injuries among male students; conversely, bruises (16 cases) and fractures (10 cases) were the most prevalent PA-related injuries among female students. Fifty-nine participants (36 males and 23 females) reported experiencing two or more types of PA-related injuries. The limbs were the most injured parts of the body in boys (18 cases for upper limbs and 79 cases for lower limbs), while the head and lower limbs were the most vulnerable parts in girls (respectively, 12 and 34 cases). Of all the injuries that occurred, only 43 cases (33 boys and 10 girls) required urgent medical intervention. | PMC10001543 | |
3.2. Knowledge of PA-Related Injuries | Participants’ average correct answer score was 10.31 ± 3.68, with 10.57 ± 3.97 for boys and 10.03 ± 3.34 for girls. The analysis of the individual values shows that 33.3% of respondents had a low competence level (score of 1 to 8 points), 61.7% had an intermediate competence level (score of 9 to 16 points), and only 5% of respondents had a good level of competence (at least 17 points).The one-way ANOVA test showed that levels of knowledge about PA-related injuries were almost similar across all age groups. However, significant differences were noted among participants stratified by BMI categories ( | PMC10001543 | ||
3.3. Sedentary Behaviors | The mean SB score for participants was 2.716 ± 0.61, with 2.79 ± 0.596 for boys and 2.64 ± 0.67 for girls ( | PMC10001543 | ||
3.4. Weekly Physical Activity | The average PA score of the participants was 2.45 ± 0.86 (boys = 2.32 ± 0.9; girls = 2.58 ± 0.8) indicating that our participants ranged from inactive to moderately active. The | PMC10001543 | ||
3.5. Regressions | fits | REGRESSION | Logistic regression was performed to determine the effects of gender, age, BMI, fat mass, lean mass, knowledge of PA-related injuries, SB, and level of PA on the likelihood of having PA-related injuries in general and the likelihood that the injury will require emergency medical attention. The logistic regression model was statistically significant, χThe logistic regression model was also statistically significant for the need for medical care after PA-related injury, χAnalysis of dependent variables with more than two categories (questions 2, 3, and 4) was performed using multinomial logistic regression with gender, age, BMI, fat mass, lean mass, knowledge of PA-related injuries, SB, and level of PA as independent variables and “Not injured” as the reference category. Pearson’s chi-square statistic indicated that the model fitted well with data on the number of PA-related injuries sustained, χRegarding types of PA-related injuries, Pearson’s chi-square statistic indicated that the model fits the data well, χRegarding the injured body parts, fit testing indicated that the model fit the data well, χ | PMC10001543 |
4. Discussion | concussions, fractures, injuries, weight loss, sports-related injuries, bruises, upper extremity injury | MINOR, COMPLICATIONS, BROWN | The purpose of this study was two-fold: (1) to assess the frequency of PA-related injuries among Saudi students aged 13–18 to determine the location of the injury in the body area, the types of injuries, and whether or not the injury required urgent medical attention, and (2) to investigate the association of these factors with gender, age, BMI, the student’s extent of knowledge about PA-related injuries, level of SB, and their weekly PA.Results revealed that boys were at higher risk for injury than girls, 57.28% of boys and 33.67% of girls reported having suffered PA-related injuries over the past year. Recorded values were greater than those noted by Cai et al. [According to our findings, three factors might contribute to the elevated overall incidence and gender discrepancy: first, a low overall level of PA was reported among participants, more in boys than girls; second, a reduced knowledge of PA-related injuries was seen among participants; and third, a higher SB was reported in boys compared to girls. The difference in fat-free mass between boys and girls and the maturity stage might also contribute partly to the occurrence of some types of PA-related injuries.Note that these results were expected and reasonable given the limited access of Saudi women to sports and PA. Indeed, various social and religious conditions have made women’s sports in Saudi Arabia a controversial topic for many years due to the suppression of women’s participation in sports by conservative authorities. Saudi women were not allowed to play sports in public places, go to school alone, or engage in recreational activities with or in front of men. The first sports center dedicated to girls in Saudi Arabia was established in 2013, offering training programs including fitness, karate, yoga, weight loss, and special activities for children.Unlike boys, physical education has just been introduced into the education system for girls, and it is not yet implemented in all schools. The physical education program in girls’ schools was approved in 2017 with the aim of boosting sports activities among all members of Saudi society, one of the goals of the Kingdom’s Vision 2030. In a recent systematic review of the prevalence of inactivity and perceived barriers to active living, Al-Hazzaa [Results also demonstrated that bruises and strains were the most common types of sports injuries among boys, while bruises and fractures were the most common injuries among girls. Among subjects, 32.07% of the injured participants reported having suffered at least two types of injuries. The limbs were the most injured body parts in boys, while the head and lower limbs were the most vulnerable parts in girls. Regarding the injuries, 23.37% required urgent medical attention. Participants aged 15 to 17 years were more vulnerable to repeated injuries (three or more) in various parts of the body (two or more), mainly the head and trunk.The growth and development of adolescents have implications for specific risks of sports-related injuries. Growth and development can also impact short- and long-term complications of sports-related injuries [Knowledge of PA-related injuries is also a relevant factor in preventing the occurrence of injuries. The results found negative associations between knowledge of PA-related injuries and all variables related to injury frequency, location, and types, except bruises and strains compared to no injuries. However, knowledge of PA-related injuries cannot be studied independently of cognitive development in general. According to Brown et al. [The data also revealed that SB were associated with a greater likelihood of developing a number and type of sports injuries: for every one-point increase in SB, the likelihood of being injured increased by 1.431, having an injury that requires medical intervention by 1.87, suffering three or more sports injuries by 2.274, having strains by 2.001, having concussions by 3.936, having two or more types of injuries by 1.666, and having an upper extremity injury by 2.302. Cairncross et al. [Several limitations of this study should be considered. First, because our data are self-reported, recall and reporting biases are unavoidable. Students can clearly remember late and serious injuries but easily forget earlier and minor injuries [ | PMC10001543 |
5. Conclusions | fractures, injuries, bruises | Findings revealed that boys were 3.52 times more likely to have PA-related injuries than girls. More specific knowledge was associated with a lower likelihood of sustaining a PA-related injury. In contrast, increased SB was associated with a greater likelihood of sustaining a PA-related injury. Bruises and strains were the most common types of sports injuries among boys, while bruises and fractures were the most common injuries among girls. The limbs were the most injured body parts in boys, whereas the head and lower limbs were the most vulnerable parts in girls. Of the injuries reported, 23.37% required urgent medical attention and participants aged 15 to 17 were the most vulnerable to repetitive injuries (three or more) in various body parts (two or more), primarily the head and the trunk. | PMC10001543 | |
Author Contributions | Methodology, M.A.S., A.A.A. and M.S.A.; validation, M.A.S., A.A.A. and M.S.A.; formal analysis, M.A.S., A.A.A. and M.S.A.; investigation, M.A.S. and A.A.A.; data curation, M.A.S., A.A.A. and M.S.A.; writing—original draft preparation, M.A.S. and A.A.A.; writing—review and editing, M.A.S.; supervision, M.S.A.; project administration, A.A.A.; funding acquisition, M.S.A. All authors have read and agreed to the published version of the manuscript. | PMC10001543 | ||
Institutional Review Board Statement | The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the Deanship of Scientific Research, King Faisal University (Ref. No. KFU-REC-2021-OCT-EA00019). | PMC10001543 | ||
Informed Consent Statement | Informed consent was obtained from all participants aged 16 or older or parents younger than 16 involved in the study. | PMC10001543 | ||
Data Availability Statement | Data can be provided on request from the corresponding authors. | PMC10001543 | ||
Conflicts of Interest | The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. | PMC10001543 | ||
References | Sedentary behaviors, injuries, sedentary behaviors | REGRESSION | Correct answer score among Saudi adolescents aged 13–18, who suffered injuries in the last year, stratified by the number of injuries (Sedentary behaviors score among Saudi adolescents aged 13–18, who suffered injuries in the last year, stratified by the number of injuries (Physical activity score among Saudi adolescents aged 13–18, who suffered injuries in the last year, stratified by the number of injuries that occurred (Anthropometric characteristics of Saudi students aged 13–18, stratified by gender.Data are means and standard deviation. BMI = body mass index; PBF = percentage body fat.Knowledge of physical activity-related injuries, sedentary behaviors, and level of physical activity among Saudi students aged 13–18, stratified by sex, age, BMI categories, frequency, and types of injuries.Knowledge of physical activity-related injuries, sedentary behaviors, and level of physical activity among Saudi students aged 13–18, stratified by sex × age and sex × BMI categories.Logistic regression model for individual predictors of the likelihood of sustaining physical activity-related injuries and those requiring urgent medical attention among Saudi students aged 13–18.Note: * Multinomial logistic regression model for individual predictors of the number of injuries related to physical activity, their types, and injured body parts, among Saudi students aged 13–18.Note: * | PMC10001543 |
Purpose | IRON DEFICIENCY | To compare the efficacy of intravenous (IV) iron (ferric derisomaltose) with oral iron (ferrous fumarate) in women 14–21 weeks pregnant with persistent iron deficiency (ferritin < 30 µg/L). | PMC10435604 | |
Methods | fatigue | ADVERSE EVENTS, IRON DEFICIENCY | In a single-centre, open-label, randomised controlled trial at a Danish hospital, women with persistent iron deficiency after routine oral iron treatment were allocated to receive 1000 mg IV iron (single-dose) or 100 mg elemental oral iron daily. Outcomes were assessed during an 18-week follow-up period. The primary endpoint was the proportion of non-anaemic (haemoglobin [Hb] ≥ 11 g/dL) women throughout follow-up. Other outcomes included changes in haematological parameters, patient-reported fatigue, and quality of life (QoL). Safety was assessed by recording adverse events. | PMC10435604 |
Results | From July 2017 to February 2020, 100 women were randomised to IV iron and 101 to oral iron. Throughout follow-up, 91% of women were non-anaemic in the IV iron group compared with 73% in the oral iron group (18% difference [95% confidence interval 0.10–0.25]; | PMC10435604 | ||
Conclusion | anaemia, fatigue | ANAEMIA, IRON DEFICIENCY | IV iron was superior in preventing anaemia compared with oral iron in pregnant women with persistent iron deficiency; biochemical superiority was accompanied by improved fatigue and QoL. | PMC10435604 |
Clinical trial registration | MAY | European Clinical Trials Database: EudraCT no.: 2017-000776-29 (3 May 2017); ClinicalTrials.gov: NCT03188445 (13 June 2017).The trial protocol has been published: | PMC10435604 | |
Supplementary Information | The online version contains supplementary material available at 10.1007/s00404-022-06768-x. | PMC10435604 | ||
Keywords | PMC10435604 | |||
What does this study add to the clinical work | PMC10435604 | |||
Introduction | Worldwide, about 38% of pregnant women are anaemic (haemoglobin [Hb] < 11.0 g/dL) [During pregnancy, iron requirements increase due to placental growth, foetal development and enhanced erythropoiesis [Oral iron is frequently used in the routine treatment of ID and IDA in pregnant women. It is inexpensive, but often poorly tolerated, which can compromise compliance [ | PMC10435604 | ||
Methods | PMC10435604 | |||
Study design, setting and population | anaemia, hypersensitivity, infections | ANAEMIA, HYPERSENSITIVITY, INFECTIONS, MULTIPLE ALLERGIES | A single-centre, open-label, randomised, comparative trial was conducted between July 2017 and February 2020 at the Department of Obstetrics and Gynaecology, Copenhagen University Hospital Hvidovre, Denmark. The department employed routine screening for ID and anaemia in the first trimester by measuring Hb and ferritin levels. ID was defined as a ferritin level < 30 µg/L—a threshold with good diagnostic accuracy for determining low storage iron [Participants were randomly assigned to receive either a single dose of IV iron (ferric derisomaltose [FDI], also known as iron isomaltoside; MonoferKey inclusion criteria included: women aged ≥ 18 years; pregnant in the second trimester (gestational age 14–21 weeks, inclusive); persistent ID (ferritin < 30 µg/L) after four weeks of treatment with oral iron. Exclusion criteria included multiple pregnancies, a history of multiple allergies, known hypersensitivity to any of the excipients in the investigational drugs, active infections, and recent red blood cell (RBC) transfusion. All randomised participants had four scheduled follow-up visits at 3, 6, 12 and 18 weeks post baseline. | PMC10435604 |
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