Incidence and Laboratory Predictors of Acute Ischemic Stroke in COVID-19: A Cross-Sectional Study

Articles in Press

Document Type : Original Article

Authors

Department of Emergency Medicine, Kerman University of Medical Sciences, Kerman, Iran

Abstract

Background: The possibility of central nervous system (CNS) involvement following Coronavirus Disease 2019 (COVID-19) is rare. Laboratory tests may play a predictive role in the occurrence of stroke.
 
Objective: The objectives of this study were twofold: first, to investigate the incidence of acute stroke, and second, to examine the role of laboratory tests in predicting the occurrence of these events following infection.
 
Methods: This cross-sectional study was conducted over one year. The inclusion criteria were as follows: patients over 18 years of age with a positive multiple polymerase chain reaction (RT-PCR) test result or typical lung CT findings of confirmed cases of pneumonia due to COVID-19 and who had undergone a brain CT scan due to suspicion of brain damage. The patients were divided into two groups, with and without brain damage, and compared with each other. The chi-square test was employed to evaluate the correlation between the qualitative variables, while the Mann-Whitney U test and the Student's t-test were applied to analyze the quantitative variables. Subsequently, logistic regression analysis was conducted to examine the association between patient outcomes and the pertinent variables. A p-value of less than 0.05 was established as indicative of statistical significance. Data analysis was conducted using SPSS.
 
Results: Among the 6604 patients, 98 underwent brain CT scans, of which 9.18% had stroke. Notably, 0.55% of all patients had acute ischemic stroke, a proportion that was significantly higher in women than in men. A statistically significant difference was observed in blood glucose (BG) and activated partial thromboplastin time (aPTT) levels among patients with ischemic stroke compared to those without stroke (p < 0.05). In both univariate and multivariate analyses with logistic regression, the three variables gender, blood glucose, and aPTT were significantly associated with the incidence of ischemic stroke. The Area Under the Curve (AUC) values for BG and aPTT were determined to be 0.66 and 0.67, respectively.
 
Conclusion: The incidence of acute stroke following COVID-19 infection is not common. In female patients, decreased blood glucose and decreased aPTT were associated with an increased incidence of ischemic stroke following infection.

Keywords

Acknowledgements: This study was supported by the Clinical Research Center of Afzalipour Academic Hospital, Kerman University of Medical Science, Kerman, Iran.

 

Availability of data and materials: The dataset presented in the study is available on request from the corresponding author during submission or after its publication.

 

Conflicts of interests: The authors declared no potential conflicts of interest.

 

Consent for publication: Not applicable.

 

Ethics approval and consent to participate: The Kerman University of Medical Sciences ethics committee approved the study protocol with the number of IR.KMU.AH.REC.1403.040, which complies with the declaration of Helsinki.

 

Financial disclosure: No funding.

 

Author contributions: Study concept, design, and supervision: M.T, S.AS, M.A. Acquisition of data: M.A. Analysis and interpretation of data: M.T. Drafting of the manuscript, technical and material support: M.T, S.AS, M.A.

 

Open Access Policy: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/

References

1. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet. 2020; 28;395(10229):1054-62.
https://doi.org/10.1016/S0140-6736(20)30566-3
PMid:32171076
 
2. Gąsecka A, Borovac JA, Guerreiro RA, Giustozzi M, Parker W, Caldeira D, Chiva-Blanch G. Thrombotic complications in patients with COVID-19: pathophysiological mechanisms, diagnosis, and treatment. Cardiovascular drugs and therapy. 2021;35:215-29.
https://doi.org/10.1007/s10557-020-07084-9
PMid:33074525 PMCid:PMC7569200  
 
3. Lodigiani C, Iapichino G, Carenzo L, Cecconi M, Ferrazzi P, Sebastian T, Kucher N, Studt JD, Sacco C, Bertuzzi A, Sandri MT. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thrombosis research. 2020; 1;191:9-14.
https://doi.org/10.1016/j.thromres.2020.04.024
PMid:32353746 PMCid:PMC7177070  
 
4. Ahmad I, Rathore FA. Neurological manifestations and complications of COVID-19: A literature review. Journal of Clinical Neuroscience. 2020; 1;77:8-12.
https://doi.org/10.1016/j.jocn.2020.05.017
PMid:32409215 PMCid:PMC7200361  
 
5. Al-Ani F, Chehade S, Lazo-Langner A. Thrombosis risk associated with COVID-19 infection. A scoping review. Thrombosis research. 2020; 1;192:152-60.
https://doi.org/10.1016/j.thromres.2020.05.039
PMid:32485418 PMCid:PMC7255332  
 
6. Antunez Muinos PJ, Lopez Otero D, Amat-Santos IJ, Lopez Pais J, Aparisi A, Cacho Antonio CE, Catalá P, Gonzalez Ferrero T, Cabezón G, Otero Garcia O, Gil JF. The COVID-19 lab score: an accurate dynamic tool to predict in-hospital outcomes in COVID-19 patients. Scientific Reports. 2021; 30;11(1):9361.
https://doi.org/10.1038/s41598-021-88679-6
PMid:33931677 PMCid:PMC8087839  
 
7. Xie J, Hungerford D, Chen H, Abrams ST, Li S, Wang G, Wang Y, Kang H, Bonnett L, Zheng R, Li X. Development and external validation of a prognostic multivariable model on admission for hospitalized patients with COVID-19. MedRxiv. 2020, 30:2020-03.
https://doi.org/10.1101/2020.03.28.20045997  
 
8. Lu J, Hu S, Fan R, Liu Z, Yin X, Wang Q, Lv Q, Cai Z, Li H, Hu Y, Han Y. ACP risk grade: a simple mortality index for patients with confirmed or suspected severe acute respiratory syndrome coronavirus 2 disease (COVID-19) during the early stage of outbreak in Wuhan, China. MedRxiv. 2020; 23:2020-02.
https://doi.org/10.2139/ssrn.3543603
https://doi.org/10.1101/2020.02.20.20025510  
 
9. Zhang S, Guo M, Duan L, Wu F, Hu G, Wang Z, Huang Q, Liao T, Xu J, Ma Y, Lv Z. Development and validation of a risk factor-based system to predict short-term survival in adult hospitalized patients with COVID-19: a multi-center, retrospective, cohort study. Critical Care. 2020 ;24:1-3.
https://doi.org/10.1186/s13054-020-03123-x
PMid:32678040 PMCid:PMC7364297  
 
10. Macias-Muñoz L, Wijngaard R, González-de la Presa B, Bedini JL, Morales-Ruiz M, Jiménez W. Value of clinical laboratory test for early prediction of mortality in patients with COVID-19: the BGM score. Journal of circulating biomarkers. 2021;10:1.
https://doi.org/10.33393/jcb.2021.2194
PMid:33717357 PMCid:PMC7890680  
 
11. Norouzi-Barough L, Asgari Khosroshahi A, Gorji A, Zafari F, Shahverdi Shahraki M, Shirian S. COVID-19-induced stroke and the potential of using mesenchymal stem cells-derived extracellular vesicles in the regulation of neuroinflammation. Cellular and Molecular Neurobiology. 2023;43(1):37-46.
https://doi.org/10.1007/s10571-021-01169-1
PMid:35025001 PMCid:PMC8755896  
 
12. Sadeghmousavi S, Rezaei N. COVID-19 infection and stroke risk. Reviews in the Neurosciences. 2021;32(3):341-9.
https://doi.org/10.1515/revneuro-2020-0066
PMid:33580645  
 
13. Wang W, Sun Q, Bao Y, Liang M, Meng Q, Chen H, Li J, Wang H, Li H, Shi Y, Li Z. Analysis of risk factors for thromboembolic events in 88 patients with COVID-19 pneumonia in Wuhan, China: a retrospective descriptive report. Medical science monitor: international medical journal of experimental and clinical research. 2021;27:e929708-1.
https://doi.org/10.12659/MSM.929708  
 
14. Han H, Yang L, Liu R, Liu F, Wu KL, Li J, Liu XH, Zhu CL. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clinical Chemistry and Laboratory Medicine (CCLM). 2020;58(7):1116-20.
https://doi.org/10.1515/cclm-2020-0188
PMid:32172226  
 
15. Zhang Y, Xiao M, Zhang S, Xia P, Cao W, Jiang W, Chen H, Ding X, Zhao H, Zhang H, Wang C. Coagulopathy and antiphospholipid antibodies in patients with Covid-19. New England Journal of Medicine. 2020;382(17):e38.
https://doi.org/10.1056/NEJMc2007575
PMCid:PMC7161262  
 
16. Pranata R, Huang I, Lim MA, Wahjoepramono EJ, July J. Impact of cerebrovascular and cardiovascular diseases on mortality and severity of COVID-19-systematic review, meta-analysis, and meta-regression. Journal of stroke and cerebrovascular diseases. 2020 ; 29(8):104949.
https://doi.org/10.1016/j.jstrokecerebrovasdis.2020.104949
PMCid:PMC7221373  
 
17. Gupta N, Zhao YY, Evans CE. The stimulation of thrombosis by hypoxia. Thrombosis research. 2019;181:77-83.
https://doi.org/10.1016/j.thromres.2019.07.013
PMid:31376606  
 
18. Qin C, Zhou L, Hu Z, Yang S, Zhang S, Chen M, Yu H, Tian DS, Wang W. Clinical characteristics and outcomes of COVID-19 patients with a history of stroke in Wuhan, China. Stroke. 2020;51(7):2219-23.
https://doi.org/10.1161/STROKEAHA.120.030365
PMid:32466735 PMCid:PMC7282412  
 
19. Ji XY, Ma Y, Shi NN, Liang N, Chen RB, Liu SH, Shi S, Wu GH, Li JK, Chen H, Wang JW. Clinical characteristics and treatment outcome of COVID-19 patients with stroke in China: A multi-center retrospective study. Phytomedicine. 2021;81:153433.
https://doi.org/10.1016/j.phymed.2020.153433
PMid:33373925 PMCid:PMC7836955  
 
20. Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?. The Lancet respiratory medicine. 2020;8(4):e21.
https://doi.org/10.1016/S2213-2600(20)30116-8
PMid:32171062  
 
21. Kreutz R, Algharably EA, Azizi M, Dobrowolski P, Guzik T, Januszewicz A, Persu A, Prejbisz A, Riemer TG, Wang JG, Burnier M. Hypertension, the renin-angiotensin system, and the risk of lower respiratory tract infections and lung injury: implications for COVID-19: European Society of Hypertension COVID-19 Task Force Review of Evidence. Cardiovascular research. 2020;116(10):1688-99.
https://doi.org/10.1093/cvr/cvaa097
PMid:32293003 PMCid:PMC7184480  
 
22. Lippi G, Wong J, Henry BM. Hypertension and its severity or mortality in Coronavirus Disease 2019 (COVID-19): a pooled analysis. Pol Arch Intern Med. 2020;130(4):304-9.
https://doi.org/10.20452/pamw.15272
PMid:32231171  
 
23. Luo W, Liu X, Bao K, Huang C. Ischemic stroke associated with COVID-19: a systematic review and meta-analysis. Journal of Neurology. 2022:1-0.  
 
24. Avula A, Nalleballe K, Narula N, Sapozhnikov S, Dandu V, Toom S, Glaser A, Elsayegh D. COVID-19 presenting as stroke. Brain, behavior, and immunity. 2020;87:115-9.
https://doi.org/10.1016/j.bbi.2020.04.077
PMid:32360439 PMCid:PMC7187846  
 
25. Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, Chang J, Hong C, Zhou Y, Wang D, Miao X. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA neurology. 2020;77(6):683-90.
https://doi.org/10.1001/jamaneurol.2020.1127
PMid:32275288 PMCid:PMC7149362  
 
26. Li Y, Li M, Wang M, Zhou Y, Chang J, Xian Y, Wang D, Mao L, Jin H, Hu B. Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study. Stroke and vascular neurology. 2020;5(3).
https://doi.org/10.1136/svn-2020-000431
PMid:32616524 PMCid:PMC7371480  
 
27. Oxley TJ, Mocco J, Majidi S, Kellner CP, Shoirah H, Singh IP, De Leacy RA, Shigematsu T, Ladner TR, Yaeger KA, Skliut M. Large-vessel stroke as a presenting feature of Covid-19 in the young. New England Journal of Medicine. 2020;382(20):e60.
https://doi.org/10.1056/NEJMc2009787
PMid:32343504 PMCid:PMC7207073  
 
28. Beyrouti R, Adams ME, Benjamin L, Cohen H, Farmer SF, Goh YY, Humphries F, Jäger HR, Losseff NA, Perry RJ, Shah S. Characteristics of ischaemic stroke associated with COVID-19. Journal of Neurology, Neurosurgery & Psychiatry. 2020;91(8):889-91.
https://doi.org/10.1136/jnnp-2020-323586
PMid:32354768 PMCid:PMC7231545  
 
29. Janes F, Sozio E, Gigli GL, Ripoli A, Sbrana F, Kuris F, Nesi L, Semenzin T, Bertolino G, Deana C, Bagatto D. Ischemic strokes in COVID-19: risk factors, obesity paradox, and distinction between trigger and causal association. Frontiers in Neurology. 2023;14:1222009.
https://doi.org/10.3389/fneur.2023.1222009
PMid:37592943 PMCid:PMC10428626  
 
30. Guo J, Guan TJ, Liu YL, Chao BH, Wang LD. Gender-specific factors of ischemic stroke among atrial fibrillation patients. Zhonghua yu Fang yi xue za zhi [Chinese Journal of Preventive Medicine]. 2019;53(11):1136-40.  
 
31. Hu J, Lin JH, Jiménez MC, Manson JE, Hankinson SE, Rexrode KM. Plasma estradiol and testosterone levels and ischemic stroke in postmenopausal women. Stroke. 2020;51(4):1297- 300.
https://doi.org/10.1161/STROKEAHA.119.028588
PMid:32078496 PMCid:PMC7159036  
 
32. Magdy Beshbishy A, Oti VB, Hussein DE, Rehan IF, Adeyemi OS, Rivero-Perez N, Zaragoza-Bastida A, Shah MA, Abouelezz K, Hetta HF, Cruz-Martins N. Factors behind the higher COVID-19 risk in diabetes: a critical review. Frontiers in Public Health. 2021;9:591982.
https://doi.org/10.3389/fpubh.2021.591982
PMid:34307267 PMCid:PMC8292635  
 
33. Aziz F, Aberer F, Bräuer A, Ciardi C, Clodi M, Fasching P, Karolyi M, Kautzky-Willer A, Klammer C, Malle O, Pawelka E. COVID-19 in-hospital mortality in people with diabetes is driven by comorbidities and age-propensity score-matched analysis of Austrian national public health institute data. Viruses. 2021;13(12):2401.
https://doi.org/10.3390/v13122401
PMid:34960670 PMCid:PMC8705658  
 
34. Gogu AE, Motoc AG, Stroe AZ, Docu Axelerad A, Docu Axelerad D, Pârv F, Munteanu G, Dan F, Jianu DC. Clinical spectrum and neuroimagistic features in hospitalized patients with neurological disorders and concomitant coronavirus-19 infection. Brain Sciences. 2021; 11(9):1138.
https://doi.org/10.3390/brainsci11091138
PMid:34573160 PMCid:PMC8466125  
 
35. Gupta RD, Atri A, Mondal S, Bhattacharjee A, Garai R, Hazra AK, Choudhury B, Dutta DS, Lodh M, Ganguly A. Characterizing progressive beta-cell recovery after new-onset DKA in COVID-19 provoked A-β+ KPD (ketosis-prone diabetes): A prospective study from Eastern India. Journal of Diabetes and its Complications. 2022;36(3):108100.
https://doi.org/10.1016/j.jdiacomp.2021.108100
PMid:34916147 PMCid:PMC8656268  
 
36. Mondal S, DasGupta R, Lodh M, Gorai R, Choudhury B, Hazra AK, Ganguly A. Predictors of new-onset diabetic ketoacidosis in patients with moderate to severe COVID-19 receiving parenteral glucocorticoids: A prospective single-center study among Indian type 2 diabetes patients. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2021;15(3):795-801.
https://doi.org/10.1016/j.dsx.2021.03.022
PMid:33839639 PMCid:PMC8004476  
 
37. Jacobi J, Bircher N, Krinsley J, Agus M, Braithwaite SS, Deutschman C, Freire AX, Geehan D, Kohl B, Nasraway SA, Rigby M. Guidelines for the use of an insulin infusion for the management of hyperglycemia in critically ill patients. Critical care medicine. 2012 ; 40(12):3251-76.
https://doi.org/10.1097/CCM.0b013e3182653269
PMid:23164767  
 
38. Wang S, Ma P, Zhang S, Song S, Wang Z, Ma Y, Xu J, Wu F, Duan L, Yin Z, Luo H. Fasting blood glucose at admission is an independent predictor for 28-day mortality in patients with COVID-19 without previous diagnosis of diabetes: a multi-center retrospective study. Diabetologia. 2020;63(10):2102-11.
https://doi.org/10.1007/s00125-020-05209-1
PMid:32647915 PMCid:PMC7347402  
 
39. Fadini GP, Morieri ML, Boscari F, Fioretto P, Maran A, Busetto L, Bonora BM, Selmin E, Arcidiacono G, Pinelli S, Farnia F. Newly-diagnosed diabetes and admission hyperglycemia predict COVID-19 severity by aggravating respiratory deterioration. Diabetes research and clinical practice. 2020;168:108374.
https://doi.org/10.1016/j.diabres.2020.108374
PMid:32805345 PMCid:PMC7428425  
 
40. Mondal S, DasGupta R, Lodh M, Garai R, Choudhury B, Hazra AK, Mondal A, Ganguly A. Stress hyperglycemia ratio, rather than admission blood glucose, predicts in-hospital mortality and adverse outcomes in moderate-to-severe COVID-19 patients, irrespective of pre-existing glycemic status. Diabetes Research and Clinical Practice. 2022;190:109974.
https://doi.org/10.1016/j.diabres.2022.109974
PMid:35809688 PMCid:PMC9259189  
 
41. Wang J, Chen J. Infection with COVID-19 is a risk factor for poor prognosis in patients with intracranial hemorrhage: a prospective observational cohort study. Medicine. 2023; 102(45):e35716.
https://doi.org/10.1097/MD.0000000000035716
PMid:37960736 PMCid:PMC10637543  
 
42. Shi Y, Zheng Z, Wang P, Wu Y, Liu Y, Liu J. Development and validation of a predicted nomogram for mortality of COVID-19: a multi-center retrospective cohort study of 4,711 cases in multiethnic. Frontiers in Medicine. 2023;10:1136129.
https://doi.org/10.3389/fmed.2023.1136129
PMid:37724179 PMCid:PMC10505438  
 
43. Borzì V, Frasson S, Gussoni G, Di Lillo M, Gerloni R, Augello G, Gulli G, Ceriello A, Solerte B, Bonizzoni E, Fontanella A. Risk factors for hypoglycemia in patients with type 2 diabetes, hospitalized in internal medicine wards: findings from the FADOI-DIAMOND study. Diabetes Research and Clinical Practice. 2016;115:24-30.
https://doi.org/10.1016/j.diabres.2016.01.020
PMid:27242119  
 
44. Norris T, Razieh C, Yates T, Zaccardi F, Gillies CL, Chudasama YV, Rowlands A, Davies MJ, McCann GP, Banerjee A, Docherty AB. Admission blood glucose level and its association with cardiovascular and renal complications in patients hospitalized with COVID-19. Diabetes Care. 2022;45(5):1132-40.
https://doi.org/10.2337/dc21-1709
PMid:35275994 PMCid:PMC9174963  
 
45. Yu TM, Lin CL, Chang SN, Sung FC, Kao CH. Increased risk of stroke in patients with chronic kidney disease after recurrent hypoglycemia. Neurology. 2014;83(8):686-94.
https://doi.org/10.1212/WNL.0000000000000711
PMid:25031280  
 
46. Katz JM, Libman RB, Wang JJ, Filippi CG, Sanelli P, Zlochower A, Gribko M, Pacia SV, Kuzniecky RI, Najjar S, Azhar S. COVID-19 severity and stroke: correlation of imaging and laboratory markers. American Journal of Neuroradiology. 2021;42(2):257-61.
https://doi.org/10.3174/ajnr.A6920
PMid:33122216 PMCid:PMC7872163  
 
47. Moin AS, Al-Qaissi A, Sathyapalan T, Atkin SL, Butler AE. Platelet protein-related abnormalities in response to acute hypoglycemia in type 2 diabetes. Frontiers in Endocrinology. 2021;12:651009.
https://doi.org/10.3389/fendo.2021.651009
PMid:33859620 PMCid:PMC8043308  
 
48. Akirov A, Amitai O, Masri-Iraqi H, Diker-Cohen T, Shochat T, Eizenberg Y, Shimon I. Predictors of hypoglycemia in hospitalized patients with diabetes mellitus. Internal and emergency medicine. 2018;13:343-50.
https://doi.org/10.1007/s11739-018-1787-0
PMid:29340912  
 
49. Lee AK, Lee CJ, Huang ES, Sharrett AR, Coresh J, Selvin E. Risk factors for severe hypoglycemia in black and white adults with diabetes: the Atherosclerosis Risk in Communities (ARIC) study. Diabetes Care. 2017;40(12):1661-7.
https://doi.org/10.2337/dc17-0819
PMid:28928117 PMCid:PMC5711330  
 
50. Kapoor R, Timsina LR, Gupta N, Kaur H, Vidger AJ, Pollander AM, Jacobi J, Khare S, Rahman O. Maintaining blood glucose levels in range (70-150 mg/dL) is difficult in COVID-19 compared to non-COVID-19 ICU patients-a retrospective analysis. Journal of Clinical Medicine. 2020 ;9(11):3635.
https://doi.org/10.3390/jcm9113635
PMid:33198177 PMCid:PMC7697842  
 
51. Klok FA, Kruip MJ, Van der Meer NJ, Arbous MS, Gommers DA, Kant KM, Kaptein FH, van Paassen J, Stals MA, Huisman MV, Endeman H. Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: an updated analysis. Thrombosis research. 2020 July 1;191:148-50.
https://doi.org/10.1016/j.thromres.2020.04.041
PMid:32381264 PMCid:PMC7192101  
 
52. Qiu F, Wu Y, Zhang A, Xie G, Cao H, Du M, Jiang H, Li S, Ding M. Changes of coagulation function and risk of stroke in patients with COVID‐19. Brain and Behavior. 2021;11(6):e02185.
https://doi.org/10.1002/brb3.2185
PMid:33998177 PMCid:PMC8209810  
 
53. Warkentin TE, Kaatz S. COVID-19 versus HIT hypercoagulability. Thrombosis research. 2020;196:38-51.
https://doi.org/10.1016/j.thromres.2020.08.017
PMid:32841919 PMCid:PMC7416717  
 
54. Cui S, Chen S, Li X, Liu S, Wang F. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. Journal of Thrombosis and Haemostasis. 2020;18(6):1421-4.
https://doi.org/10.1111/jth.14830
PMid:32271988 PMCid:PMC7262324  
 
55. Fraissé M, Logre E, Pajot O, Mentec H, Plantefève G, Contou D. Thrombotic and hemorrhagic events in critically ill COVID-19 patients: a French monocenter retrospective study. Critical Care. 2020;24:1-4.
https://doi.org/10.1186/s13054-020-03361-z
https://doi.org/10.1186/s13054-020-03025-y
PMid:32487122 PMCid:PMC7265664  
 
56. Statsenko Y, Al Zahmi F, Habuza T, Neidl-Van Gorkom K, Zaki N. Prediction of COVID-19 severity using laboratory findings on admission: informative values, thresholds, ML model performance. BMJ open. 2021; 1;11(2):e044500.
https://doi.org/10.1136/bmjopen-2020-044500
PMid:33637550 PMCid:PMC7918887  
Razavi International Journal of Medicine

Articles in Press, Accepted Manuscript
Available Online from 01 June 2025

Files

Share

How to cite

Statistics