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. 2023 Jan 26;15(1):e34253. doi: 10.7759/cureus.34253

Risk Factors of Hospital-Acquired Pneumonia Among Hospitalized Patients With Cardiac Diseases

Mona Alfares 1, Atheer Almrzouqi 2,, Rana Alghamdi 2, Raghad Alsharif 2, Layan Kurdi 2, Sara Kamfar 2, Fatmah Alzahrani 2, Leen Maimani 2
Editors: Alexander Muacevic, John R Adler
PMCID: PMC9886362  PMID: 36726767

Abstract

Background

To our knowledge, no studies have been done in Saudi Arabia to determine the risk factors of hospital-acquired pneumonia (HAP) among hospitalized cardiac patients. This study aimed to assess these risk factors.

Methods

A retrospective study was done at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia. Five hundred hospitalized patients diagnosed with pre-existing cardiovascular disease (CVD) were included. A checklist was used to collect data about patients' demographic characteristics; BMI; smoking and alcohol abuse; type of cardiac disease; other chronic diseases; exposure to immunosuppressives; chemotherapy and radiotherapy in the last six months; glucocorticoid use; application of ventilator; initial, follow-up chest X-ray results; pneumonia vaccination status; nasogastric tube use; general anesthesia received; use of loop diuretics; presence of pulmonary diseases; levels of WBC, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP); results of blood and respiratory cultures; number of hospitalizations and intensive care unit (ICU) admissions in the last six months; and Richmond Agitation and Sedation Scale (RASS) score.

Results

The prevalence of pneumonia was 7%. Females; patients with autoimmune diseases who were exposed to immunosuppressives or glucocorticoids; those with an initial or second abnormal chest X-ray; patients who used nasogastric tube, had pulmonary disease, and had high levels of WBC, ESR, or CRP; and patients hospitalized for more than two times had a significantly higher percentage of having pneumonia. Abnormal second chest X-ray, high ESR, and more than two times of hospitalization within the last six months were the risk factors of pneumonia on multivariate logistic regression analysis.

Conclusion

Better prevention and intervention programs are needed to assess the risk factors of pneumonia among admitted cardiac patients.

Keywords: cardiac, hospitalized, pneumonia, acquired, hospital, risk

Introduction

Cardiovascular diseases (CVDs) are chronic diseases that necessitate immediate medical attention when it deteriorates. They include coronary artery disease (CAD), heart failure (HF), cerebrovascular disease, aortic disease (AD), and peripheral vascular disease (PVD) [1,2]. The majority of CVD patients are older and at a high risk of developing hospital-acquired pneumonia (HAP) [3].

Hospital-acquired pneumonia (HAP) is a serious medical condition that manifests as a nosocomial infection 48 hours after admission to the hospital, resulting in increased morbidity and mortality [4-6].

Pneumonia risk was linked to cardiovascular diseases such as chronic heart failure [7]. Mechanical ventilation is the most significant risk factor for developing HAP. Other risk factors for HAP include advanced age, severe underlying illness, long duration of hospital stay, and antibiotic use. HAP is associated with significant mortality. In addition, patients with HAP are subject to increased length of stay in the intensive care unit (ICU) [8].

According to previous studies, HAP incidence is 5.8% among elderly patients in the United Kingdom [9]. The prevalence of HAP was approximately 8% in hospitalized patients with acute heart failure (AHF) [10]. Large-scale cross-sectional survey of nosocomial infections in China showed that the incidence of hospital-acquired infection ranged from 3.22% to 5.22% in hospitalized patients, and the incidence of hospital-acquired lower respiratory tract infection was 1.76%-1.94% [11]. While in other studies, pneumonia-related hospitalization in patients with pre-existing heart failure was 2.72% [12].

Therefore, the presence of HAP in hospitalized patients must be acknowledged. To our knowledge, no study has evaluated HAP risk factors among hospitalized CVD patients in Saudi Arabia.

Hospital-acquired pneumonia is a common respiratory disorder that has a significant impact on the safe recovery of hospitalized patients with cardiovascular disorders. The present study aimed to determine the risk factors of hospital-acquired pneumonia in patients with CVDs.

Materials and methods

We conducted a retrospective study at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia, of 500 patients who were admitted from January 2015 to December 2020. The study was approved by the Ethics Committee at King Abdulaziz University (approval number: 484-21).

The inclusion criteria were hospitalized patients above 18 years of age who were admitted to KAUH with a pre-existing cardiovascular disease. The exclusion criteria were patients with no pre-existing cardiovascular disease.

Data was retrieved from the hospital's database (Phoenix) to include patients with cardiac disorders. The included disorders were as follows: all cases of heart failure, non-rheumatic mitral (valve) insufficiency, non-rheumatic mitral (valve) stenosis, aortic (valve) insufficiency or stenosis, acute and subacute infective endocarditis, acute myocardial infarction (MI), angina pectoris, cardiac arrhythmia, atrial fibrillation and flutter, hypertensive heart disease with (congestive) heart failure, chronic ischemic heart disease, supraventricular tachycardia, palpitations, essential (primary) hypertension, cardiac arrest, either hemorrhagic or ischemic stroke, congestive heart failure, atherosclerotic heart disease of the native coronary artery, and ischemic cardiomyopathy.

A pre-designed checklist was prepared to collect data about patients' demographic characteristics (gender, age, and nationality), BMI, smoking and alcohol abuse, type of cardiac disease, chronic diseases, exposure to immunosuppressives, chemotherapy and radiotherapy in the last six months, glucocorticoid use, application of ventilator, initial and second chest X-ray results, and pneumonia vaccine status. Data about nasogastric tube use; receiving general anesthesia; using loop diuretics; the presence of pulmonary diseases; levels of WBC, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP); results of blood and respiratory cultures; the number of hospitalizations and ICU admissions in the last six months; Richmond Agitation and Sedation Scale (RASS) score (number of sedation days on and off); and the type of pneumonia was also collected.

Data was analyzed statistically using Statistical Package for Social Sciences (SPSS) version 26 (IBM SPSS Statistics, Armonk, NY). To assess the relationship between variables, qualitative data was expressed as numbers and percentages, and the chi-squared (χ2) test was used. Quantitative data was expressed as mean and standard deviation (mean ± SD). To assess the risk factors of pneumonia among the studied cardiac patients, multivariate logistic regression analysis was done, and the odds ratio was calculated at a 95% confidence interval (CI). A p-value of 0.05 was considered statistically significant.

Results

Table 1 shows patients' characteristics; 90.6% were 45 years and above. The incidence of obesity was high (38.6%).

Table 1. Distribution of the studied patients according to their demographic characters, BMI, and smoking and alcohol abuse (N = 500).

NA: not applicable

Variable Number (%)
Age  
17-30 8 (1.6)
31-45 39 (7.8)
Above 45 453 (90.6)
Gender  
Female 200 (40)
Male 300 (60)
Nationality  
Non-Saudi 283 (56.6)
Saudi 217 (43.4)
BMI  
18.5 to <25 (healthy weight) 132 (26.4)
25 to <30 (overweight) 168 (33.6)
30 or higher (obese) 193 (38.6)
Less than 18.5 (underweight) 7 (1.4)
Smoking  
Ex-smoker 49 (9.8)
NA 65 (13)
Never 315 (63)
Current smoker 71 (14.2)
Alcohol abuse  
Ex-abuser 3 (0.6)
NA 115 (23)
Never 377 (75.4)
Current abuser 5 (1)

Table 2 shows a comorbidity profile of the study. Heart failure and hypertension were commonly found. Many patients were at risk of having compromised immunity: diabetes mellitus (DM) and previous chemotherapy, radiotherapy, and glucocorticoid therapy.

Table 2. Distribution of the studied patients according to the type of cardiac disease, chronic diseases, exposure to immunosuppressives, chemotherapy and radiotherapy in the last six months, glucocorticoid use, the application of ventilator, initial and second chest X-ray results, and pneumonia vaccine status.

NA, not applicable; MI, myocardial infarction; HTN, hypertension; DM, diabetes mellitus

Variable Number (%)
Type of cardiac disease  
Heart failure 363 (72.6)
Mitral regurgitation 5 (1)
Mitral stenosis 5 (1)
Aortic regurgitation 1 (0.2)
Aortic stenosis 10 (2)
MI 113 (22.6)
Arrhythmia 70 (14)
Ischemic heart disease 160 (32)
HTN 400 (80)
DM 346 (69.2)
Autoimmune diseases 13 (2.6)
Exposure to immunosuppressives 27 (5.4)
Exposure to chemotherapy within the last six months 14 (2.8)
Exposure to radiation therapy within the last six months 5 (1)
Glucocorticoid use 97 (19.4)
Application of ventilator  
NA 43 (8.6)
No 439 (87.8)
Yes 18 (3.6)
Initial chest X-ray  
Abnormal 100 (20)
NA 222 (44.4)
Normal 178 (35.6)
Second chest X-ray during hospitalization  
Abnormal "consolidation" 63 (12.6)
NA 324 (64.8)
Normal 113 (22.6)
Pneumonia vaccine  
NA 488 (97.6)
No 10 (2)
Yes 2 (0.4)

Table 3 shows ICU procedures: nasogastric tube and general anesthesia; aspiration pneumonia, chronic pulmonary disease, multiple ICU readmissions, and increased length of hospital stay were encountered in patients with HAP.

Table 3. Distribution of the studied patients according to nasogastric tube use; receiving general anesthesia; using loop diuretics; the presence of pulmonary diseases; levels of WBC, ESR, and CRP; results of blood and respiratory cultures; the number of hospitalization and ICU admission in the last six months; RASS score (number of sedation days on and off); and the type of pneumonia.

NA, not applicable; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; ICU, intensive care unit; RASS, Richmond Agitation and Sedation Scale; AMS, altered mental status; HAP, hospital-acquired pneumonia; VAP, ventilator-associated pneumonia 

Variable Number (%)
Nasogastric tube use  
NA 32 (6.4)
No 452 (90.4)
Yes 16 (3.2)
Receiving general anesthesia  
No 399 (78.8)
Yes 101 (20.2)
Using loop diuretics  
No 131 (26.2)
Yes 369 (73.8)
Pulmonary diseases  
No 375 (75)
Yes 125 (25)
Leukocyte (WBC) count  
High 79 (15.8)
Low 37 (7.4)
Missing 4 (0.8)
Normal 380 (76)
ESR  
High 70 (14)
Low 5 (1)
Missing 324 (64.8)
Normal 101 (20.2)
CRP  
High 204 (40.8)
Low 14 (2.8)
Missing 255 (51)
Normal 27 (5.4)
Blood culture  
NA 307 (61.4)
No organism 193 (38.6)
Respiratory culture  
Endotracheal tube 7 (1.4)
NA 392 (78.4)
Nasopharyngeal swap 10 (2)
Normal 52 (10.4)
Sputum "bacteria" 38 (6.7)
Suction 1 (0.2)
Number of hospitalization within the last six months  
Two times 65 (13)
Less than two times 216 (43.2)
NA 13 (2.6)
More than two times 132 (26.4)
No 74 (14.8)
Number of ICU admission within the last six months  
NA 126 (25.2)
More than nine 1 (0.2)
No 373 (74.6)
RASS score (number of sedation days)  
One-hour AMS, confusion, generalized weakness, and dysarthria 1 (0.2)
NA 415 (83)
No 81 (16.2)
Sedation 3 (0.6)
Number of sedation days off 1.76 ± 2.57
How many days was the patient ventilated  
NA 255 (51)
More than 10 3 (0.6)
No ventilation 242 (48.4)
Type of pneumonia  
Diagnosed with HAP 30 (85.7)
Diagnosed with VAP 1 (2.8)
Diagnosed with aspiration pneumonia 11 (31.4)

Figure 1 illustrated that the prevalence of pneumonia among the studied cardiac patients was 7%.

Figure 1. Percentage distribution of pneumonia prevalence among the studied patients.

Figure 1

Tables 4-5 show that female patients (11.5%) and those having autoimmune diseases (23.1%) and exposure to immunosuppressives (22.2%) and using glucocorticoid (14.4%) had an abnormal initial (15%) or second chest X-ray (25.4%). In addition, patients who used nasogastric tube (50%) had a presence of pulmonary disease (16%) or had high levels of WBC (15.2%), ESR (15.7%), and CRP (11.8%); those whose respiratory culture had bacteria in sputum (28.9%) and who were hospitalized for more than two times (15.9%) had a significant higher risk of hospital-acquired pneumonia (p ≤ 0.05) (Table 6).

Table 4. Relationship between the prevalence of pneumonia and patients' demographic characters, BMI, and smoking and alcohol abuse.

NA, not applicable; χ2, chi-squared

Variable Pneumonia χ2 P-value
Present number (%) Absent number (%)
Age  
17-30 0 (0.0) 8 (100) 1.95 0.376
31-45 1 (2.6) 38 (97.4)
Above 45 34 (7.5) 419 (92.5)
Gender  
Female 23 (11.5) 177 (88.5) 10.36 0.001
Male 12 (4) 288 (96)
Nationality  
Non-Saudi 22 (7.8) 261 (92.2) 0.6 0.439
Saudi 13 (6) 204 (94)
Smoking
Ex-smoker 3 (6.1) 46 (93.9) 1.25 0.74
NA 3 (4.6) 62 (95.4)
Never 25 (7.9) 290 (92.1)
Current smoker 4 (5.6) 67 (94.4)
Alcohol abuse  
Ex-abuser 0 (0.0) 3 (100) 1.99 0.573
NA 11 (9.6) 104 (90.4)
Never 24 (6.4) 353 (93.6)
Current abuser 0 (0.0) 5 (100)

Table 5. Relationship between the prevalence of pneumonia and the type of cardiac disease, chronic diseases, exposure to immunosuppressives, chemotherapy and radiotherapy in the last six months, glucocorticoid use, the application of ventilator, initial and second chest X-ray results, and pneumonia vaccine status.

NA, not applicable; MI, myocardial infarction; HTN, hypertension; DM, diabetes mellitus; χ2, chi-squared

Variable Pneumonia χ2 P-value
Present number (%) Absent number (%)
Type of cardiac disease  
Heart failure 29 (8) 334 (92) 1.99 0.158
Mitral regurgitation 1 (20) 4 (80) 1.31 0.252
Mitral stenosis 0 (0.0) 5 (100) 0.38 0.538
Aortic regurgitation 0 (0.0) 1 (100) 0.07 0.784
Aortic stenosis 1 (10) 9 (90) 0.14 0.707
MI 3 (2.7) 110 (97.3) 4.23 0.04
Arrhythmia 6 (8.6) 64 (91.4) 0.3 0.578
Ischemic heart disease 7 (4.4) 153 (95.6) 2.49 0.115
HTN 30 (7.5) 370 (92.5) 0.8 0.668
DM 29 (8.4) 317 (91.6) 3.31 0.19
Autoimmune diseases 3 (23.1) 10 (76.9) 5.29 0.021
Exposure to immunosuppressives 6 (22.2) 21 (77.8) 10.39 0.006
Exposure to chemotherapy within the last six months 3 (21.4) 11 (78.6) 4.6 0.032
Exposure to radiation therapy within the last six months 1 (20) 4 (80) 1.31 0.252
Glucocorticoid use 14 (14.4) 83 (85.6) 10.21 0.001
Application of ventilator 4 (22.2) 14 (77.8) 7.24 0.027
Initial chest X-ray  
Abnormal 15 (15) 85 (85) 12.41 0.002
NA 12 (5.4) 210 (94.6)
Normal 8 (4.5) 170 (95.5)
Second chest X-ray during hospitalization  
Abnormal "consolidation" 16 (25.4) 47 (74.6) 38.14 <0.001
NA 16 (4.9) 308 (95.1)
Normal 3 (2.7) 110 (97.3)
Pneumonia vaccine 0 (0.0) 2 (100) 0.29 0.865

Table 6. Relationship between the prevalence of pneumonia and nasogastric tube use; receiving general anesthesia; using loop diuretics; the presence of pulmonary diseases; levels of WBC, ESR, and CRP; results of blood and respiratory cultures; the number of hospitalization and ICU admission in the last six months; RASS score (number of sedation days on and off); and the type of pneumonia.

NA, not applicable; χ2, chi-squared; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; ICU, intensive care unit; RASS, Richmond Agitation and Sedation Scale; AMS, altered mental status

Variable Pneumonia χ2 P-value
Present number (%) Absent number (%)
Nasogastric tube use        
NA 3 (9.4) 29 (90.6) 47.7 <0.001
No 24 (5.3) 428 (94.7)
Yes 8 (50) 8 (50)
Receiving general anesthesia 8 (7.9) 93 (92.1) 0.16 0.685
Using loop diuretics 24 (6.5) 345 (93.5) 0.53 0.466
Pulmonary diseases        
No 15 (4) 360 (96) 20.73 <0.001
Yes 20 (16) 105 (84)
Leukocyte (WBC) count        
High 12 (15.2) 67 (84.8) 11.6 0.009
Low 4 (10.8) 33 (89.2)
Missing 0 (0.0) 4 (100)
Normal 19 (5) 361 (95)
ESR        
High 11 (15.7) 59 (84.3) 9.75 0.021
Low 0 (0.0) 5 (100)
Missing 18 (5.6) 306 (94.4)
Normal 6 (5.9) 95 (94.1)
CRP        
High 24 (11.8) 180 (88.2) 12.89 0.005
Low 0 (0.0) 14 (100)
Missing 9 (3.5) 246 (96.5)
Normal 2 (7.4) 25 (92.6)
Blood culture        
NA 20 (6.5) 287 (93.5) 0.28 0.592
No organism 15 (7.8) 178 (92.2)
Respiratory culture        
Endotracheal tube 1 (14.3) 6 (85.7) 41.17 <0.001
NA 18 (4.6) 374 (95.4)
Nasopharyngeal swap 3 (30) 7 (70)
Normal 2 (3.8) 50 (96.2)
Sputum "bacteria" 11 (28.9) 27 (71.1)
Suction 0 (0.0) 1 (100)
Number of hospitalization within the last six months        
Two times 5 (7.7) 60 (92.3) 24.69 <0.001
Less than two times 5 (2.3) 211 (97.7)
NA 0 (0.0) 13 (100)
More than two times 21 (15.9) 111 (84.1)
No 4 (5.4) 70 (94.6)
Number of ICU admission within the last six months        
NA 15 (11.9) 111 (88.1) 6.26 0.044
More than nine 0 (0.0) 1 (100)
No 20 (5.4) 353 (94.6)
RASS score (number of sedation days)        
One-hour AMS, confusion, generalized weakness, and dysarthria 0 (0.0) 1 (100) 1.48 0.685
NA 27 (6.5) 388 (93.5)
No 8 (9.9) 73 (90.1)
Sedation 0 (0.0) 3 (100)
Number of sedation days off 1 (0.001) 1.79 (2.6) 0.71 0.882
How many days was the patient ventilated        
NA 14 (5.5) 241 (94.5) 2.16 0.339
More than 10 0 (0.0) 3 (100)
No ventilation 21 (8.7) 221 (91.3)

Table 7 showed that on doing the multivariate logistic regression analysis to assess the risk factors of pneumonia among the studied patients, having more than two times of hospitalization within the last six months was an independent predictor of pneumonia among the studied cardiac patients.

Table 7. Multivariate logistic regression analysis of the risk factors of pneumonia among the studied cardiac patients.

CI, confidence interval; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; ICU, intensive care unit

Variable B Wald P-value Odds ratio (95% CI)
Gender 0.19 0.16 0.686 0.82 (0.32-2.11)
Autoimmune diseases 1.46 1.89 0.169 4.31 (0.53-34.69)
Exposure to immunosuppressives 0.99 0.176 0.184 2.69 (0.62-11.62)
Glucocorticoid use 0.17 0.1 0.752 0.84 (0.29-2.43)
Initial chest X-ray 0.74 1.02 0.312 0.47 (0.11-2.01)
Second chest X-ray during hospitalization: abnormal "consolidation" 2.13 5.71 0.017 8.44 (1.46-48.63)
Nasogastric tube use 3.42 1.09 0.002 30.78 (3.57-65.25)
Pulmonary diseases 1.42 7.08 0.008 4.15 (1.45-11.87)
Leukocyte (WBC) count 1.01 3.52 0.06 0.36 (0.12-1.04)
ESR 1.76 4.92 0.026 0.17 (0.03-0.81)
CRP 0.44 0.18 0.667 0.15 (0.2-3.71)
Respiratory culture 0.02 0.13 0.76 0.1 (0.02-1.1)
Number of hospitalization within the last six months 2.07 10.94 0.001 7.98 (2.33-27.53)
Number of ICU admission within the last six months 0.25 0.26 0.61 1.29 (0.47-3.5)

Discussion

Previous studies found that the magnitude of risk for pneumonia associated with CVDs was higher in patients aged above 45 years. In addition, the majority of patients are males with comorbidities, such as hypertension, diabetes, and autoimmune disease [13,14].

Life-threatening conditions such as multiple trauma, complicated chronic disease, comorbidities, and state of unconsciousness and also the need for ICU admissions and related treatment methods such as mechanical ventilation and nasogastric tube placement, as well as age and smoking, have been identified as potential risk factors for HAP in several studies [15-17].

The present work revealed that 31.4% of the patients developed aspiration pneumonia after being hospitalized. A prior study looked into ventilator-associated pneumonia (VAP). It was shown that due to the decrease in physiological and immune capabilities, older patients frequently have many comorbidities, which can lead to an increase in hospital length of stay and mechanical ventilation time, increasing the risk of VAP. In patients with mental disorders, the length of stay in the hospital and the time spent on mechanical breathing were much longer. Invasive operations in the ICU have expanded in tandem with the lengthening of hospital stays, increasing patient exposure to the bacterial environment. As a result, the likelihood of VAP has considerably increased. VAP's onset and progression have been aided by the independence and interaction of these elements [18].

Our study showed that patients who were admitted to the ICU and used glucocorticoids, antibiotics, and loop diuretics were at higher risk to develop HAP. The same association between ICU admission and pneumonia was found in a previous study [19].

Diuretic medications may theoretically improve respiratory health outcomes in chronic obstructive pulmonary disease (COPD) through a variety of pathways, but they may also cause respiratory injury by having the ability to raise serum bicarbonate and arterial pH, which can reduce peripheral and central chemoreceptor activity. As a result, hypercapnia is associated with increased risks of respiratory morbidity and mortality in older people according to previous research [20-22].

Age, malnutrition, steroid use, chronic renal failure, anemia, unconsciousness, comorbidity, recent hospitalization, and thoracic surgery are all risk factors for HAP in non-ICU patients [23-25].

In the current study, up to 7% of individuals with CVDs developed pneumonia in which 85.7% of them were diagnosed with HAP; the majority of them were hypertensive (80%). Furthermore, myocardial infarction was found to be significantly related to pneumonia (p = 0.04). On the other hand, heart failure and arrhythmia were discovered to be insignificantly associated with pneumonia. Comparing to a previous case-control study, 36 hospitalized patients with cardiovascular disease and pneumonia were matched with 36 controls who also had cardiovascular disease but did not have pneumonia. Only heart failure was found to be an independent risk factor for pneumonia among all cardiovascular disorders [26].

Patients with HAP were shown to have a history of ICU admission in previous investigations, and multilevel regression analysis revealed that the ICU department was substantially linked with the prevalence of HAP [27,28]. In Western countries, approximately 1.5% of all hospitalized patients developed HAP, while 8.3% of elderly hospitalized patients developed HAP [27].

A limitation of the present study could be the retrospective nature of the study design and the presence of incomplete medical records for some patients.

Conclusions

Our study evaluated the attributed factors of hospital-acquired pneumonia in cardiovascular disease patients. Pneumonia was found to be present in 7% of individuals with cardiac diseases, and it was shown that HAP was identified as relatively high in hospitalized patients, as well as several associated factors including gender, ICU admission, MI, exposure to immunosuppressives, and glucocorticoid use. Comprehensive, preventive, and intervention strategies are required to assess risk factors for pneumonia in hospitalized cardiac patients.

The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus.

The authors have declared that no competing interests exist.

Human Ethics

Consent was obtained or waived by all participants in this study. The Ethics Committee at King Abdulaziz University issued approval 484-21

Animal Ethics

Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue.

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