Trial of Cardiovascular Risk Factor Assessment and Transthoracic Echocardiography Results in Patients with Primary Antibody Deficiency.

The life expectancy and the risk of developing cardiovascular diseases in patients with inborn errors of immunity are systematically increasing. The aim of the study was to assess cardiovascular risk factors and to evaluate the heart in echocardiography in patients with primary antibody deficiency (PAD). Cardiac echography and selected cardiovascular risk factors, including body mass index, sedentary lifestyle, nicotine, glucose, C-reactive protein, lipid profile, uric acid level, certain chronic diseases, and glucocorticoid use, were analyzed in 94 patients >18 years of age with PAD. Of the patients,25.5% had a cardiovascular disease (mostly hypertension, 18%), 10.5% smoked, 17% were overweight, 14% were obese, and 15% were underweight. Abnormal blood pressure was found in 6.5% of the patients. Lipid metabolism disorders were found in 72.5% of in the studied cohort, increased total cholesterol (45.5%), non-high-density lipoprotein (HDL) (51%), low-density lipoprotein (LDL) (47%), and triglycerides (32%) were observed. Furthermore, 28.5% had a decrease in HDL and 9.5% had a history of hyperuricemia. The average number of risk factors was 5 ± 3 for the entire population and 4 ± 2 for those under 40 years of age. Elevated uric acid levels were found de novo in 4% of participants. In particular, 74.5% of the patients had never undergone an echocardiogram with a successful completion rate of 87% among those tested. Among them, 30% showed parameters within normal limits, primarily regurgitation (92.5%). New pathologies were identified in 28% of patients. Prevention in patients with PAD, aimed at reducing cardiovascular risk, should be a priority.

Cardiovascular Risk Awareness, Exercise Practices and Metabolic Outcomes among Patients with Diabetes Mellitus in Northern Nigeria: A Cross-sectional, Multicentre Study.

BACKGROUND: Physical exercise helps to mitigate cardiovascular risks in people with diabetes mellitus (DM), but there are limited data in Nigeria. This study aimed to assess cardiovascular risk awareness, exercise practices and metabolic outcomes among Nigerians with diabetes. MATERIALS AND METHODS: We conducted a cross-sectional study at five tertiary hospitals using questionnaire interviews and clinical assessments. Participants' knowledge of cardiovascular risk factors and knowledge of exercise were assessed on 12- and 5-item scores, while exercise practices were classed as adequate if performed regularly on 3 or more days weekly for a total of 150 min or more based on the American Diabetes Association recommendations. Mean body mass index (BMI), blood pressure (BP), fasting blood glucose, serum haemoglobin A1C (HbA1c), lipid profile, urea, creatinine and uric acid were then compared among participant groups. RESULTS: We studied 426 participants with DM, 58.7% females. The mean age was 52.9 ± 13.1 years, with males significantly older than females (54.6 ± 12.2 vs. 51.8 ± 13.5 years; 95% confidence interval: 0.27-5.28, P = 0.03). The mean age at diabetes diagnosis was 44.8 ± 11.7 years, and the median duration of diabetes was 84 months. There was low knowledge of cardiovascular risk factors and low knowledge of exercise (mean scores of 2.94 and 2.31, respectively). Forty-three per cent of participants reported adequate exercise, which was significantly associated with younger age (P = 0.007), male gender (P = 0.001) and formal education (P = 0.021). Participants with adequate exercise had lower systolic BP and serum urea compared to those with inadequate exercise, but there were no significant differences in BMI, fasting glucose, HbA1c, serum lipids, creatinine or uric acid. CONCLUSION: Participants had low knowledge of cardiovascular risks and the appropriate exercise practices for diabetes patients. There is a need for better patient education on diabetes self-care and exercise at clinic visits.

From cardiovascular protection to cardiovascular risk: the metamorphosis of menopausal hormone therapy.

Over the last 70years, oestrogen therapy for the management of menopausal symptoms has undergone a metamorphosis from perceived cardiovascular protection to perceived cardiovascular risk. The former perception is based on the convincing evidence from the Nurses' Health Study cohorts and the epidemiological data surrounding early menopause. The latter, and later, perception is based on the disquieting results from two randomised controlled studies, the Heart and Estrogen/Progestin Replacement Study (HERS) and the Women's Health Initiative study (WHI). The reality is probably more nuanced than the conclusions presented by any of these studies. When face to face with a patient, the clinician must negotiate the appropriate decision pathway around the interaction between cardiovascular risk, cardiovascular disease, menopause, and oestrogen +/-progestogen-containing hormone therapy.

Cardiovascular risk and physical activity in Syrians living in England compared with the population of North West England: a cross-sectional study.

OBJECTIVE: This study aims to assess the 10-year cardiovascular risk and physical activity among Syrians residing in England and compare them with the North West England population. DESIGN: Cross-sectional study. SETTING: Bilingual online questionnaire distributed through social media platforms from 21 June to 23 July 2023. PARTICIPANTS: Syrian individuals in England (aged 25-69, migrated post-2010) and residents of North West England within the same age bracket. All participants had no history of cardiovascular disease (CVD). PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome measures included differences in QRISK3 score, 10-year relative risk (RR), metabolic equivalent of task (MET) and self-reported physical activity between the two groups. Secondary outcome measures included subgroup analyses based on sex and age. RESULTS: Of the 273 eligible participants (137 in the Syrian group and 136 in the Northwest England group), the QRISK3 score was twofold higher in the Syrian group (2.20, 5.50) than in the North West England group (1.20, 3.15) (p=0.042). The 10-year RR was approximately three times higher in the Syrian group (p<0.001), while MET was about twice as high in the Northwest England group (p<0.001). CONCLUSIONS: Despite relocating to England, Syrians face substantially elevated cardiovascular risks attributed to an unhealthy lifestyle, including smoking, reduced physical activity, increased body mass index and diabetes, coupled with a strong family history of CVD in first-degree relatives under the age of 60. The study underscores the need for early assessment, risk factor identification and tailored interventions for this population. Raising awareness, particularly in the context of smoking, and promoting physical activity are crucial for mitigating cardiovascular risks. The findings emphasise the importance of culturally sensitive interventions to address the unique health challenges of Syrians in the UK.

Cardiovascular risk among community members in three communities in the Cape Metropole of the Western Cape.

BACKGROUND:  Cardiovascular diseases pose a risk to population health in South Africa and are responsible for almost one in six deaths (17.3%). AIM:  To determine the cardiovascular risk among community members who attended a community outreach programme. SETTING:  Three communities in the Cape Metropole of the Western Cape. METHODS:  A health survey was conducted with 783 participants, 18 years and older, conveniently sampled. The survey included questions about cardiovascular risk factors, and biometric measurements of blood pressure (BP), height and weight were conducted. RESULTS:  A total of 777 participants were included in the study. Most participants were female (529, 68.1%), with an average age of 42.3 years (s.d. 14.2). Risk behaviours reported included smoking (216, 27.8%), consuming more than two drinks of alcohol daily (78, 10%), low physical activity (384, 49.4%), being stressed on most days (436, 56.1%) and unhealthy eating habits (253, 32.6%). More than half of the participants (402, 51.7%) had a body mass index (BMI) ≥ 30, 26.0% (202) had a systolic BP of ≥ 140 mm Hg and 22.4% (174) had a diastolic BP of ≥ 90 mm Hg; 16.6% (130) had a cardiovascular disease (CVD) risk of 10-20 and 19.3% (150) had a CVD risk of 20%. CONCLUSION:  Nearly a fifth of the participants had a significant probability of developing heart disease or experiencing a stroke over the next 10 years.Contribution: There is an urgent need for comprehensive health promotion and behaviour change interventions focused on reducing CVD risk factors at the community level.

Eliminação dos ácidos graxos trans de produção industrial: instrumento para redação de regulamentos

O consumo de ácidos graxos trans é uma das principais causas de morbidade e mortalidade em todo o mundo. Os ácidos graxos trans não têm benefícios conhecidos para a saúde e são uma das principais causas de doenças cardíacas em todo o mundo. Estima-se que os ácidos graxos trans causem cerca de 260.000 mortes a cada ano. Para reduzir efetivamente o consumo de ácidos graxos trans, a Organização Pan-Americana da Saúde/Organização Mundial da Saúde recomenda que todos os países eliminem os ácidos graxos trans produzidos industrialmente (IP-TFA) de seu abastecimento alimentar nacional, que constituem a principal fonte de ácidos graxos trans em Nutrição humana. Esta publicação foi elaborada para auxiliar agências governamentais e ministérios no desenvolvimento ou alteração de legislação ou regulamentação nacional com o objetivo de eliminar o IP-TFA do abastecimento de alimentos em seu país. Embora útil para leitores com formação jurídica, esta publicação também se destina a um público não jurídico que deseja promover a eliminação do AGT-IP por meio de regulamentação. As perguntas da árvore de decisão são usadas para ajudar os usuários desta ferramenta a preencher um regulamento de remoção de TFA-IP específico do contexto que seja consistente com as melhores práticas da OPAS/OMS. Abrange disposições importantes que devem ser consideradas no texto do regulamento, como as que dão autoridade legal para adotar um regulamento sobre ácidos graxos trans, a definição do escopo do regulamento, a criação de um quadro de fiscalização e o cumprimento de o regulamento. , e o estabelecimento de uma data de vigência. Esta publicação inclui um modelo de regulamento e oferece uma visão prática dos principais aspectos legais da remoção do AGT-IP, com foco em abordagens comprovadas, eficazes e baseadas em evidências. Ele orienta os leitores sobre como redigir regulamentos para implementar as políticas de remoção de TFA-IP recomendadas pela OPAS/OMS, bem como disposições complementares que se mostraram eficazes.

Exploring machine learning strategies for predicting cardiovascular disease risk factors from multi-omic data.

BACKGROUND: Machine learning (ML) classifiers are increasingly used for predicting cardiovascular disease (CVD) and related risk factors using omics data, although these outcomes often exhibit categorical nature and class imbalances. However, little is known about which ML classifier, omics data, or upstream dimension reduction strategy has the strongest influence on prediction quality in such settings. Our study aimed to illustrate and compare different machine learning strategies to predict CVD risk factors under different scenarios. METHODS: We compared the use of six ML classifiers in predicting CVD risk factors using blood-derived metabolomics, epigenetics and transcriptomics data. Upstream omic dimension reduction was performed using either unsupervised or semi-supervised autoencoders, whose downstream ML classifier performance we compared. CVD risk factors included systolic and diastolic blood pressure measurements and ultrasound-based biomarkers of left ventricular diastolic dysfunction (LVDD; E/e' ratio, E/A ratio, LAVI) collected from 1,249 Finnish participants, of which 80% were used for model fitting. We predicted individuals with low, high or average levels of CVD risk factors, the latter class being the most common. We constructed multi-omic predictions using a meta-learner that weighted single-omic predictions. Model performance comparisons were based on the F1 score. Finally, we investigated whether learned omic representations from pre-trained semi-supervised autoencoders could improve outcome prediction in an external cohort using transfer learning. RESULTS: Depending on the ML classifier or omic used, the quality of single-omic predictions varied. Multi-omics predictions outperformed single-omics predictions in most cases, particularly in the prediction of individuals with high or low CVD risk factor levels. Semi-supervised autoencoders improved downstream predictions compared to the use of unsupervised autoencoders. In addition, median gains in Area Under the Curve by transfer learning compared to modelling from scratch ranged from 0.09 to 0.14 and 0.07 to 0.11 units for transcriptomic and metabolomic data, respectively. CONCLUSIONS: By illustrating the use of different machine learning strategies in different scenarios, our study provides a platform for researchers to evaluate how the choice of omics, ML classifiers, and dimension reduction can influence the quality of CVD risk factor predictions.

Long-Term Cardiovascular Risk Associated With Treatment of Attention-Deficit/Hyperactivity Disorder in Adults.

BACKGROUND: Incrementing numbers of patients treated for attention-deficit/hyperactivity disorder (ADHD) call for scrutiny concerning long-term drug-safety. OBJECTIVES: This study aims to investigate associations between long-term use of ADHD treatment and cardiovascular outcomes. METHODS: Using nationwide registers, adult patients first-time initiated on ADHD treatment between 1998 and 2020 were identified. Exposure groups were prior users, <1 defined daily dose (DDD) per day, ≥1 DDD per day determined at start of follow-up, and 1 year after patients' first claimed prescription. Outcomes were acute coronary syndromes, stroke, heart failure, and a composite of the above. RESULTS: At start of follow-up, 26,357, 31,211, and 15,696 individuals were correspondingly categorized as prior users (42% female, median age: 30 years [Q1-Q3: 23-41 years]), <1 DDD per day (47% female, median age: 31 years [Q1-Q3: 24-41 years]), and ≥1 DDD per day (47% female, median age: 33 years [Q1-Q3: 25-41 years]), respectively. Comparing ≥1 DDD per day with prior users, elevated standardized 10-year absolute risk of stroke (2.1% [95% CI: 1.8%-2.4%] vs 1.7% [95% CI: 1.5%-1.9%]), heart failure (1.2% [95% CI: 0.9%-1.4%] vs 0.7% [95% CI: 0.6%-0.8%]), and the composite outcome (3.9% [95% CI: 3.4%-4.3%] vs 3.0% [95% CI: 2.8 %-3.2%]) was found-with corresponding risk ratios of 1.2 (95% CI: 1.0-1.5), 1.7 (95% CI: 1.3-2.2), and 1.3 (95% CI: 1.1-1.5). No apparent associations were found for acute coronary syndrome (1.0% [95% CI: 0.8%-1.2%] vs 0.9% [95% CI: 0.8%-1.0%]). CONCLUSIONS: Possible associations between elevated long-term cardiovascular risk and increasing dosage of ADHD treatment use in a young patient group should warrant further investigation.

Documento de consenso sobre tabaquismo y riesgo vascular.

Consensus statement on smoking and vascular risk About 22% of the Spanish population are daily smokers. Men are more likely to smoke than women. In Spain, women between 15-25 years of age smoke as much or more than men. Every smoker should be assessed for: physical dependence on nicotine (Fagerström test), social and psychological dependence (Glover Nilsson test), level of motivation to quit (Richmond test), probability of therapy success (Henri-Mondor and Michael-Fiore tests), and stage of behavioral change development (Prochaska and DiClementi). Advice on smoking cessation is highly cost-effective and should always be provided. Smoking is an enhancer of cardiovascular risk because it acts as a pathogen agent in the development of arteriosclerosis and is associated with ischemic heart disease, stroke, and peripheral artery disease. Smoking increases the risk of chronic lung diseases (COPD) and is related to cancers of the lung, female genitalia, larynx, oropharynx, bladder, mouth, esophagus, liver and biliary tract, and stomach, among others. Combined oral contraceptives should be avoided in women smokers older than 35 years of age due to the risk of thromboembolism. In smoking cessation, the involvement of physicians, nurses, psychologists, etc. is important, and their multidisciplinary collaboration is needed. Effective pharmacological treatments for smoking cessation are available. Combined treatments are recommended when smoker's dependence is high. For individuals who are unable to quit smoking, a strategy based on tobacco damage management with a total switch to smokeless products could be a less dangerous alternative for their health than continuing to smoke.

Impact of androgenic anabolic steroid use on cardiovascular and mental health in Danish recreational athletes: protocol for a nationwide cross-sectional cohort study as a part of the Fitness Doping in Denmark (FIDO-DK) study.

INTRODUCTION: The use of androgenic anabolic steroids (AASs) among recreational athletes is steadily increasing. However, knowledge regarding the potentially harmful effects of AAS primarily originates from case reports and small observational studies. This large-scale study aims to investigate the impact of AAS use on vascular plaque formation, preclinical coronary disease, cardiac function, circulating cardiovascular risk markers, quality of life (QoL) and mental health in a broad population of illicit AAS users. METHODS AND ANALYSES: A nationwide cross-sectional cohort study including a diverse population of men and women aged ≥18 years, with current or previous illicit AAS use for at least 3 months. Conducted at Odense University Hospital, Denmark, the study comprises two parts. In part A (the pilot study), 120 recreational athletes with an AAS history will be compared with a sex-matched and age-matched control population of 60 recreational athletes with no previous AAS use. Cardiovascular outcomes include examination of non-calcified coronary plaque volume and calcium score using coronary CT angiography, myocardial structure and function via echocardiography, and assessing carotid and femoral artery plaques using ultrasonography. Retinal microvascular status is evaluated through fundus photography. Cardiovascular risk markers are measured in blood. Mental health outcomes include health-related QoL, interpersonal difficulties, body image concerns, aggression dimensions, anxiety symptoms, depressive severity and cognitive function assessed through validated questionnaires. The findings of our comprehensive study will be used to compose a less intensive investigatory cohort study of cardiovascular and mental health (part B) involving a larger group of recreational athletes with a history of illicit AAS use. ETHICS AND DISSEMINATION: The study received approval from the Regional Committee on Health Research Ethics for Southern Denmark (S-20210078) and the Danish Data Protection Agency (21/28259). All participants will provide signed informed consent. Research outcomes will be disseminated through peer-reviewed journals and scientific conferences. TRIAL REGISTRATION NUMBER: NCT05178537.

Global Cardiovascular Risk and Associated Factors in 2792 French Military and Civilian Aircrew.

INTRODUCTION: Cardiovascular (CV) diseases are a major public health issue, the prevention of which plays a key role in promoting flight safety. However, few studies have looked at the determinants of the overall risk of CV morbidity-mortality within the various aeronautical occupations.METHODS: A monocentric, observational, cross-sectional study was based on the retrospective data collected during 6 mo at the Toulon Aeromedical Center. From October 2017 to April 2018, 2792 professional aircrew ages 18-74 were included. The overall CV risk was estimated using the European Society of Cardiology SCORE and the Framingham model, as well as a summation model.RESULTS: More than two-thirds of this mainly male population (86.2%) had no more than one CV risk factor [69.9% (68.2-71.6)]. In 82.5% of cases, this was dyslipidemia according to current European criteria [55.8% (52.4-59.1)] or smoking [26.7% (23.8-29.8)]. An overall risk level of "moderate" to "very high" concerned only one subject in five according to the SCORE model [20.1% (18.6-21.6)], one in six according to Framingham [16.3% (14.9-17.7)] and almost one in three according to the summation model [30.1% (28.4-31.9)].DISCUSSION: Multivariate analyses found no significant associations between socio-professional criteria and overall risk levels. The results have underlined the effect of dyslipidemia and smoking on early risk among applicants. Beyond the illustration of favorable cardiovascular status among aircrews related to the standards of selection and close monitoring process, areas for improvement were identified, inviting the development of prevention strategies around the "moderate" overall CV risk.Huiban N, Gehant M, Brocq F-X, Collange F, Mayet A, Monteil M. Global cardiovascular risk and associated factors in 2792 French military and civilian aircrew. Aerosp Med Hum Perform. 2024; 95(5):233-244.

Using Guidelines of Care to Lower Cardiovascular Risk in Patients with Psoriasis.

National guidelines define psoriasis as a risk enhancer for cardiovascular disease and recommend increased monitoring and more intense management of cardiovascular risk factors in these patients, who face an increased burden of cardiovascular disease morbidity and mortality. Screening for modifiable cardiovascular risk factors, including blood pressure, weight, cholesterol, glucose, and smoking, can be efficiently incorporated into routine dermatology clinical practice. Partnerships with primary care providers and preventive cardiologists are essential to improving management of cardiovascular risk in patients with psoriasis.

Correspondence to "association of sleep patterns and cardiovascular disease risk is modified by glucose tolerance status".

After reading the article written by Wang et al., we have encountered several concerns that may compromise the credibility of the article. There are some factors, such as changes in sleep patterns, glucose tolerance status, and the use of hypnotics, which may interfere with the research results. Additionally, the design of the sleep pattern could lead to biased outcomes. Therefore, we are writing this letter to recommend that further research should take these concerns into consideration.

Infrared thermography for normal endothelial function screening.

BACKGROUND: Endothelial dysfunction (ED) suspicion will allow to prevent accelerated atherosclerosis and premature death. OBJECTIVE: To establish the usefulness of thermography for endothelial function screening in adults with cardiovascular risk factors. MATERIAL AND METHODS: Cross-sectional, analytical diagnostic test. A brachial arterial diameter (BAD) increase < 11% at one-minute post-ischemia meant probable ED and was confirmed if BAD was ≥ 11% post-sublingual nitroglycerin. Thermographic photographs of the palmar region were obtained at one minute. Descriptive statistics, ROC curve, Mann-Whitney's U-test, chi-square test, or Fisher's exact test were used. RESULTS: Thirty-eight subjects with a median age of 50 years, and with 624 thermographic measurements were included. Nine had ED (flow-mediated vasodilation [FMV]: 2.5%). The best cutoff point for normal endothelial function in subjects with cardiovascular risk factors was ≥ 36 °C at one minute of ischemia, with 85% sensitivity, 70% specificity, positive and negative predictive values of 78 and 77%, area under the curve of 0.796, LR+ 2.82, LR- 0.22. CONCLUSION: An infrared thermography-measured temperature in the palmar region greater than or equal to 36 °C after one minute of ischemia is practical, non-invasive, and inexpensive for normal endothelial function screening in adults with cardiovascular risk factors.

ANTECEDENTES: La sospecha de disfunción endotelial (DE) permitirá prevenir la aterosclerosis acelerada y la muerte prematura. OBJETIVO: Establecer la utilidad de la termografía en el cribado de la función endotelial en adultos con factores de riesgo cardiovascular. MATERIAL Y MÉTODOS: Estudio transversal analítico de prueba diagnóstica. El incremento del diámetro de la arteria braquial < 11 % a un minuto posisquemia significó probable DE, confirmada si el diámetro fue ≥ 11 % posnitroglicerina sublingual. Se obtuvieron fotografías termográficas al minuto de la región palmar. Se aplicó estadística descriptiva, curva ROC, pruebas U de Mann-Whitney, chi cuadrada o exacta de Fisher. RESULTADOS: Se incluyeron 38 sujetos, mediana de edad de 50 años, con 624 mediciones termográficas; nueve presentaron DE (vasodilatación mediada por flujo de 2.5 %). El mejor punto de corte para la función endotelial normal en sujetos con factores de riesgo cardiovascular fue ≥ 36 °C al minuto de isquemia, con sensibilidad de 85%, especificidad de 70%, valores predictivos positivo y negativo de 78 y 77%, área bajo la curva de 0.796, razón de verisimilitud positiva de 2.82 y razón de verisimilitud negativa de 0.22. CONCLUSIÓN: La medición de la temperatura en la región palmar mediante termografía infrarroja ≥ 36 °C tras un minuto de isquemia es práctica, no invasiva y económica para el cribado de la función endotelial normal en adultos con factores de riesgo cardiovascular.

The effects of grape seed extract supplementation on cardiovascular risk factors, liver enzymes and hepatic steatosis in patients with non-alcoholic fatty liver disease: a randomised, double-blind, placebo-controlled study.

BACKGROUND: Despite the high antioxidant potential of grape seed extract (GSE), very limited studies have investigated its effect on non-alcoholic fatty liver disease (NAFLD). Therefore, this study was conducted with the aim of investigating the effect of GSE on metabolic factors, blood pressure and steatosis severity in patients with NAFLD. METHODS: In this double-blind randomized clinical trial study, 50 NAFLD patients were divided into two groups of 25 participants who were treated with 520 mg/day of GSE or the placebo group for 2 months. The parameters of glycemic, lipid profile, blood pressure and steatohepatitis were measured before and after the intervention. RESULTS: The GSE group had an average age of 43.52 ± 8.12 years with 15 women and 10 men, while the placebo group had an average age of 44.88 ± 10.14 years with 11 women and 14 men. After 2 months of intervention with GSE, it was observed that insulin, HOMA-IR, TC, TG, LDL-c, ALT, AST, AST/ALT, SBP, DBP and MAP decreased and QUICKi and HDL-c increased significantly (p-value for all < 0.05). Also, before and after adjustment based on baseline, the average changes indicated that the levels of insulin, HOMA-IR, TC, TG, LDL-c, SBP, DBP, MAP in the GSE group decreased more than in the control group (p for all < 0.05). Furthermore, the changes in HDL-c were significantly higher in the GSE group (p < 0.05). The between-groups analysis showed a significant decrease in the HOMA-ß and AST before and after adjustment based on baseline levels (p < 0.05). Moreover, the changes in QUICKi after adjustment based on baseline levels were higher in the GSE group than in the control group. Also, between-groups analysis showed that the severity of hepatic steatosis was reduced in the intervention group compared to the placebo group (P = 0.002). CONCLUSIONS: It seems that GSE can be considered one of the appropriate strategies for controlling insulin resistance, hyperlipidemia, hypertension and hepatic steatosis in NAFLD patients. TRIAL REGISTRATION: The clinical trial was registered in the Iranian Clinical Trial Registration Center (IRCT20190731044392N1). https://irct.behdasht.gov.ir/trial/61413 . (The registration date: 30/03/2022).