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Do antibiotic use and underlying diseases increase the risk and mortality of multidrug-resistant community-acquired pneumonia?

Yıl 2022, Cilt: 15 Sayı: 2, 229 - 237, 01.04.2022
https://doi.org/10.31362/patd.967856

Öz

Purpose: Pneumonias, which are infections of the lung parenchyma, are divided into two groups as community
acquired pneumonia (CAP) and hospital acquired pneumonia. CAP is very common and CAP can be mortal.
Healthcare-Associated Pneumonia (HAP) is defined as pneumonia that develops in patients who have used
antibiotic or hospitalization in the past three months and who are fed by a nasogastric tube. In recent studies,
the term multidrug-resistant CAP has been used instead of HAP. In this study, it was aimed to compare the
laboratory results, causative bacterial pathogens and fatality rates of CAP and multidrug-resistant CAP patients
on the first day of hospitalization.
Material and method: Patients with CAP and multi-drug-resistant CAP who were admitted to the Infectious
Diseases and Clinical Microbiology Clinic between 09/01/2018-03/20/2020 were recruited.
Results: 129 patients with CAP and 64 patients with multidrug-resistant CAP were studied. Underlying disease
was found in 96.9% (62) patients in the multidrug-resistant CAP group and in 79.8% (103) patients in the
CAP group. A significant difference was found between the two groups (p=0.003). 79.7% (51) patients in the multidrug-resistant CAP group and 19.4% (25) patients in the CAP group used antibiotics in the last three
months. It was found to be significantly higher in the multidrug-resistant CAP group (p=0.000).
Conclusion: The underlying disease and the use of antibiotics in the last three months increase the risk of
developing multidrug-resistant CAP. Mortality rate was found to be higher in this patient group. In order to
encounter less multidrug-resistant CAP problem, it is necessary to pay attention to the rules of rational use of
antibiotics in medical practice.

Kaynakça

  • 1. Niederman MS, Mandell LA, Anzueto A, Bass JB, Broughton WA, Campbell GD, Dean N, File T, Fine MJ, Gross PA, Martinez F, Marrie TJ, Plouffe JF, Ramirez J, Sarosi GA, Torres A, Wilson R, Yu VL, American Thoracic Society Guidelines for the management of adults with community-acquired pneumonia. Diagnosis, assessment of severity, antimicrobial therapy, and prevention. Am J Respir Crit Care Med. 2001; 163(7): 1730-54.
  • 2. Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM Jr, Musher DM, Niederman MS, Torres A, Whitney CG, Infectious Diseases Society of America; American Thoracic Society. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007; 44 Suppl 2(Suppl 2):S27-72.
  • 3. File TM. Community-acquired pneumonia. Lancet 2003; 362(9400):1991-2001.
  • 4. Musher DM, Thorner AR. Community-acquired pneumonia. N Engl J Med. 2014; 371(17):1619-28.
  • 5. Wunderink RG, Waterer GW. Community-acquired pneumonia. N Engl J Med. 2014; 370(6):543-51.
  • 6. Gadsby NJ, Russell CD, McHugh MP, MarkH, Morris AC, Laurenson IF, Hill AT, Templeton KE. Comprehensive Molecular Testing for Respiratory Pathogens in Community-Acquired Pneumonia. Clin Infect Dis. 2016; 62(7):817-823.
  • 7. JainS, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM, Reed C, Grijalva CG, Anderson EJ, Courtney DM, Chappell JD, Qi C, for the CDC EPIC Study Team. Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults. N Engl J Med. 2015; 373(5):415-27.
  • 8. Erbey H, Kaptan Y, Aydemir Ş, ve ark. Risk factors for drug resistant community-acquired pneumonia. Am J Respir Crit Care Med. 2017;195:A3944.
  • 9. Türk Toraks Derneği Erişkinlerde Hastanede Gelişen Pnömoni Tanı ve Tedavi Uzlaşı Raporu. 2018; 1-16.
  • 10. Restrepo MI, Anzueto A. The role of gram-negative bacteria in healthcare-associated pneumonia. Semin Respir Crit Care Med. 2009; 30(1): 61-6.
  • 11. Lam AP, Wunderink RG. The role of MRSA in healthcare-associated pneumonia. Semin Respir Crit Care Med. 2009; 30(1): 52- 60.
  • 12. Marrie TJ, Huang JQ. Epidemiology of community-acquired pneumonia in Edmonton, Alberta: an emergency department-based study. Can Respir J. 2005; 12(3):139-42.
  • 13. Ramirez JA, Wiemken TL, Peyrani P, Arnold FW, Kelley R, Mattingly WA, Nakamatsu R, Pena S, Guinn BE, Furmanek SP, Persaud AK, Raghuram A, Fernandez F, Beavin L, Bosson R, Fernandez-Botran R, Cavallazzi R, Bordon J, Valdivieso C, Schulte J, Carrico RM, University of Louisville Pneumonia Study Group. Adults Hospitalized With Pneumonia in the United States: Incidence, Epidemiology, and Mortality. Clin Infect Dis. 2017; 65(11):1806-1812.
  • 14. Niederman MS, McCombs JS, Unger AN, Kumar A, Popovian R. The cost of treating community-acquired pneumonia. Clin Ther. 1998; 20(4):820-37.
  • 15. Medicare.gov–Hospital Compare. https://www.medicare.gov/hospital compare/search.html (Accessed on April 19, 2016).
  • 16. Chalmers JD, Rother C, Salih W, Ewig S. Healthcare-associated pneumonia does not accurately identify potentially resistant pathogens: a systematic review and meta-analysis. Clin Infect Dis. 2014; 58(3):330-9.
  • 17. Gross AE, Van Schooneveld TC, Olsen KM, Rupp ME, Bui TH, Forsung E, Kalil AC. Epidemiology and predictors of multi drug-resistant community-acquired and healthcare-associated pneumonia. Antimicrob Agents Chemother. 2014; 58(9):5262-8.
  • 18. Yap V, Datta D, Metersky ML. Is the present definition of healthcare-associated pneumonia the best way to define risk of infection with antibiotic-resistant pathogens? Infect Dis Clin North Am. 2013; 27(1):1-18.
  • 19. Lopez A, Amaro R, Polverino E. Does healthcare associated pneumonia really exist? Eur J Intern Med. 2012; 23(5):407-11.
  • 20. American Thoracic Society Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005; 171(4): 388-416.
  • 21. Bartlett JG. Diagnostic tests for agents of community-acquired pneumonia. Clin Infect Dis. 2011; 52 Suppl 4:S296-304.
  • 22. JainS, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM, Reed C, Grijalva CG, Anderson EJ, Courtney DM, Chappell JD, Qi C, Hart EM, Carroll F, Trabue C, Donnelly HK, Williams DJ, Zhu Y, Arnold SR, Ampofo K, Waterer GW, Levine M, Lindstrom S, Winchell JM, Katz JM, Erdman D, Schneider E, Hicks LA, McCullers JA, Pavia AT, Edwards KM, Finelli L, CDC EPIC Study Team Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults. N Engl J Med. 2015; 373(5):415-27.
  • 23. Carratalà J, Mykietiuk A, Fernández-Sabé N, Suárez C, Dorca J, Verdaguer R, Manresa F, Gudiol F. Healthcare-associated pneumonia requiring hospital admission: epidemiology, antibiotic therapy, and clinical outcomes. Arch Intern Med. 2007; 167(13): 1393-9.
  • 24. Kollef MH, Shorr A, Tabak YP, Gupta V, Liu LZ, Johannes RS. Epidemiology and outcomes of health-care-associated pneumonia: results from a large US database of culture-positive pneumonia. Chest. 2005; 128(6): 3854-62.
  • 25. Micek ST, Kollef KE, Reichley RM, Roubinian N, Kollef MH. Healthcare-associated pneumonia and community-acquired pneumonia: a single-center experience. Antimicrob Agents Chemother. 2007; 51(10): 3568-73.
  • 26. Taşbakan MS, Bacakoğlu F, Başoğlu ÖK, Gürgün A, Başarık B, Tuncel ŞT, Sayıner A. Sağlık bakımı ile ilişkili pnömoni ve toplum kökenli pnömoni tanıları ile hastanede yatan olguların karşılaştırılması. Tüberküloz ve Toraks Dergisi 2011; 59(4): 348-354.
  • 27. Flanders SA, Stein J, Shochat G, Sellers K, Holland M, Maselli J, Drew WL, Reingold AL, Gonzales R. Performance of a bedside C-reactive protein test in the diagnosis of community-acquired pneumonia in adults with acute cough. Am J Med. 2004; 116(8):529-35.
  • 28. Holm A, Nexoe J, Bistrup LA, Pedersen SS, Obel N, Nielsen LP, Pedersen C. Aetiology and prediction of pneumonia in lower respiratory tract infection in primary care. Br J Gen Pract. 2007; 57 (540):547-54.
  • 29. Almirall J, Bolíbar I, Toran P, Pera G, Boquet X, Balanzó X, Sauca G, Community-Acquired Pneumonia Maresme Study Group. Contribution of C-reactive protein to the diagnosis and assessment of severity of community-acquired pneumonia. Chest. 2004; 125(4):1335-42.
  • 30. Boussekey N, Leroy O, Alfandari S, Devos P, Georges H, GueryB. Procalcitonin kinetics in the prognosis of severe community-acquired pneumonia. Intensive Care Med. 2006; 32(3):469-72.

Antibiyotik kullanımı ve altta yatan hastalıklar çoklu ilaca dirençli toplum kökenli pnömoni riskini ve mortaliteyi artırıyor mu?

Yıl 2022, Cilt: 15 Sayı: 2, 229 - 237, 01.04.2022
https://doi.org/10.31362/patd.967856

Öz

Amaç: Akciğer parankiminin enfeksiyonu olan pnömoniler, toplum kökenli pnömoni (TKP) ve hastane kökenli
pnömoni olarak iki gruba ayrılmaktadır. TKP oldukça sık görülür ve mortal seyredebilir. Sağlık Hizmeti İlişkili
Pnömoni (SHİP), son üç ay içinde antibiyotik kullanımı ya da hastaneye yatışı olan ve nazogastrik sonda ile
beslenen hastalarda gelişen pnömoniler olarak tanımlanmıştır. Son yapılan çalışmalarda, SHİP yerine çok ilaca
dirençli TKP terimi kullanılmaya başlanmıştır. Bu çalışmada TKP ve çok ilaca dirençli TKP hastalarının yatışlarının
ilk günü alınan laboratuvar sonuçları, etken bakteriyel patojenleri ve fatalite oranlarının karşılaştırılması
amaçlanmıştır.
Gereç ve yöntem: Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Kliniği’ne 01/09/2018-20/03/2020 tarihleri
arasında yatırılan TKP ve çok ilaca dirençli TKP hastaları alınmıştır.
Bulgular: TKP 129 hasta ve çok ilaca dirençli TKP 64 hasta incelenmiştir. Çok ilaca dirençli TKP grubunda
%96,9 (62) hastada, TKP grubunda %79,8 (103) hastada altta yatan hastalık bulunmuştur. İki grup arasında
anlamlı bir fark saptanmıştır (p=0,003). Çok ilaca dirençli TKP grubunda %79,7 (51) hasta, TKP grubunda ise
%19,4 (25) hasta son üç ay içinde antibiyotik kullanmıştır. Çok ilaca dirençli TKP grubunda anlamlı oranda
yüksek bulunmuştur (p=0,000).
Sonuç: Altta yatan hastalık ve son üç ay içinde antibiyotik kullanımı çok ilaca dirençli TKP gelişme riskini
artırmaktadır. Bu hasta grubunda mortalite oranın daha yüksek olduğu saptanmıştır. Çok ilaca dirençli TKP
sorunuyla daha az karşılaşmak için pratik hekimlik uygulamalarında akılcı antibiyotik kullanım kurallarına özen
gösterilmesi gerekmektedir.

Kaynakça

  • 1. Niederman MS, Mandell LA, Anzueto A, Bass JB, Broughton WA, Campbell GD, Dean N, File T, Fine MJ, Gross PA, Martinez F, Marrie TJ, Plouffe JF, Ramirez J, Sarosi GA, Torres A, Wilson R, Yu VL, American Thoracic Society Guidelines for the management of adults with community-acquired pneumonia. Diagnosis, assessment of severity, antimicrobial therapy, and prevention. Am J Respir Crit Care Med. 2001; 163(7): 1730-54.
  • 2. Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM Jr, Musher DM, Niederman MS, Torres A, Whitney CG, Infectious Diseases Society of America; American Thoracic Society. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007; 44 Suppl 2(Suppl 2):S27-72.
  • 3. File TM. Community-acquired pneumonia. Lancet 2003; 362(9400):1991-2001.
  • 4. Musher DM, Thorner AR. Community-acquired pneumonia. N Engl J Med. 2014; 371(17):1619-28.
  • 5. Wunderink RG, Waterer GW. Community-acquired pneumonia. N Engl J Med. 2014; 370(6):543-51.
  • 6. Gadsby NJ, Russell CD, McHugh MP, MarkH, Morris AC, Laurenson IF, Hill AT, Templeton KE. Comprehensive Molecular Testing for Respiratory Pathogens in Community-Acquired Pneumonia. Clin Infect Dis. 2016; 62(7):817-823.
  • 7. JainS, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM, Reed C, Grijalva CG, Anderson EJ, Courtney DM, Chappell JD, Qi C, for the CDC EPIC Study Team. Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults. N Engl J Med. 2015; 373(5):415-27.
  • 8. Erbey H, Kaptan Y, Aydemir Ş, ve ark. Risk factors for drug resistant community-acquired pneumonia. Am J Respir Crit Care Med. 2017;195:A3944.
  • 9. Türk Toraks Derneği Erişkinlerde Hastanede Gelişen Pnömoni Tanı ve Tedavi Uzlaşı Raporu. 2018; 1-16.
  • 10. Restrepo MI, Anzueto A. The role of gram-negative bacteria in healthcare-associated pneumonia. Semin Respir Crit Care Med. 2009; 30(1): 61-6.
  • 11. Lam AP, Wunderink RG. The role of MRSA in healthcare-associated pneumonia. Semin Respir Crit Care Med. 2009; 30(1): 52- 60.
  • 12. Marrie TJ, Huang JQ. Epidemiology of community-acquired pneumonia in Edmonton, Alberta: an emergency department-based study. Can Respir J. 2005; 12(3):139-42.
  • 13. Ramirez JA, Wiemken TL, Peyrani P, Arnold FW, Kelley R, Mattingly WA, Nakamatsu R, Pena S, Guinn BE, Furmanek SP, Persaud AK, Raghuram A, Fernandez F, Beavin L, Bosson R, Fernandez-Botran R, Cavallazzi R, Bordon J, Valdivieso C, Schulte J, Carrico RM, University of Louisville Pneumonia Study Group. Adults Hospitalized With Pneumonia in the United States: Incidence, Epidemiology, and Mortality. Clin Infect Dis. 2017; 65(11):1806-1812.
  • 14. Niederman MS, McCombs JS, Unger AN, Kumar A, Popovian R. The cost of treating community-acquired pneumonia. Clin Ther. 1998; 20(4):820-37.
  • 15. Medicare.gov–Hospital Compare. https://www.medicare.gov/hospital compare/search.html (Accessed on April 19, 2016).
  • 16. Chalmers JD, Rother C, Salih W, Ewig S. Healthcare-associated pneumonia does not accurately identify potentially resistant pathogens: a systematic review and meta-analysis. Clin Infect Dis. 2014; 58(3):330-9.
  • 17. Gross AE, Van Schooneveld TC, Olsen KM, Rupp ME, Bui TH, Forsung E, Kalil AC. Epidemiology and predictors of multi drug-resistant community-acquired and healthcare-associated pneumonia. Antimicrob Agents Chemother. 2014; 58(9):5262-8.
  • 18. Yap V, Datta D, Metersky ML. Is the present definition of healthcare-associated pneumonia the best way to define risk of infection with antibiotic-resistant pathogens? Infect Dis Clin North Am. 2013; 27(1):1-18.
  • 19. Lopez A, Amaro R, Polverino E. Does healthcare associated pneumonia really exist? Eur J Intern Med. 2012; 23(5):407-11.
  • 20. American Thoracic Society Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005; 171(4): 388-416.
  • 21. Bartlett JG. Diagnostic tests for agents of community-acquired pneumonia. Clin Infect Dis. 2011; 52 Suppl 4:S296-304.
  • 22. JainS, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM, Reed C, Grijalva CG, Anderson EJ, Courtney DM, Chappell JD, Qi C, Hart EM, Carroll F, Trabue C, Donnelly HK, Williams DJ, Zhu Y, Arnold SR, Ampofo K, Waterer GW, Levine M, Lindstrom S, Winchell JM, Katz JM, Erdman D, Schneider E, Hicks LA, McCullers JA, Pavia AT, Edwards KM, Finelli L, CDC EPIC Study Team Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults. N Engl J Med. 2015; 373(5):415-27.
  • 23. Carratalà J, Mykietiuk A, Fernández-Sabé N, Suárez C, Dorca J, Verdaguer R, Manresa F, Gudiol F. Healthcare-associated pneumonia requiring hospital admission: epidemiology, antibiotic therapy, and clinical outcomes. Arch Intern Med. 2007; 167(13): 1393-9.
  • 24. Kollef MH, Shorr A, Tabak YP, Gupta V, Liu LZ, Johannes RS. Epidemiology and outcomes of health-care-associated pneumonia: results from a large US database of culture-positive pneumonia. Chest. 2005; 128(6): 3854-62.
  • 25. Micek ST, Kollef KE, Reichley RM, Roubinian N, Kollef MH. Healthcare-associated pneumonia and community-acquired pneumonia: a single-center experience. Antimicrob Agents Chemother. 2007; 51(10): 3568-73.
  • 26. Taşbakan MS, Bacakoğlu F, Başoğlu ÖK, Gürgün A, Başarık B, Tuncel ŞT, Sayıner A. Sağlık bakımı ile ilişkili pnömoni ve toplum kökenli pnömoni tanıları ile hastanede yatan olguların karşılaştırılması. Tüberküloz ve Toraks Dergisi 2011; 59(4): 348-354.
  • 27. Flanders SA, Stein J, Shochat G, Sellers K, Holland M, Maselli J, Drew WL, Reingold AL, Gonzales R. Performance of a bedside C-reactive protein test in the diagnosis of community-acquired pneumonia in adults with acute cough. Am J Med. 2004; 116(8):529-35.
  • 28. Holm A, Nexoe J, Bistrup LA, Pedersen SS, Obel N, Nielsen LP, Pedersen C. Aetiology and prediction of pneumonia in lower respiratory tract infection in primary care. Br J Gen Pract. 2007; 57 (540):547-54.
  • 29. Almirall J, Bolíbar I, Toran P, Pera G, Boquet X, Balanzó X, Sauca G, Community-Acquired Pneumonia Maresme Study Group. Contribution of C-reactive protein to the diagnosis and assessment of severity of community-acquired pneumonia. Chest. 2004; 125(4):1335-42.
  • 30. Boussekey N, Leroy O, Alfandari S, Devos P, Georges H, GueryB. Procalcitonin kinetics in the prognosis of severe community-acquired pneumonia. Intensive Care Med. 2006; 32(3):469-72.
Toplam 30 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Bulaşıcı Hastalıklar
Bölüm Araştırma Makalesi
Yazarlar

Duygu Mert 0000-0002-6810-2199

Hasan Öksüzoğlu 0000-0002-9627-8765

Gülşen İskender 0000-0001-7619-1366

Göknur Yapar Toros 0000-0001-8256-0666

Ayla Yenigün 0000-0002-7519-313X

Mustafa Ertek 0000-0002-9397-8432

Yayımlanma Tarihi 1 Nisan 2022
Gönderilme Tarihi 8 Temmuz 2021
Kabul Tarihi 20 Ekim 2021
Yayımlandığı Sayı Yıl 2022 Cilt: 15 Sayı: 2

Kaynak Göster

APA Mert, D., Öksüzoğlu, H., İskender, G., Yapar Toros, G., vd. (2022). Antibiyotik kullanımı ve altta yatan hastalıklar çoklu ilaca dirençli toplum kökenli pnömoni riskini ve mortaliteyi artırıyor mu?. Pamukkale Medical Journal, 15(2), 229-237. https://doi.org/10.31362/patd.967856
AMA Mert D, Öksüzoğlu H, İskender G, Yapar Toros G, Yenigün A, Ertek M. Antibiyotik kullanımı ve altta yatan hastalıklar çoklu ilaca dirençli toplum kökenli pnömoni riskini ve mortaliteyi artırıyor mu?. Pam Tıp Derg. Nisan 2022;15(2):229-237. doi:10.31362/patd.967856
Chicago Mert, Duygu, Hasan Öksüzoğlu, Gülşen İskender, Göknur Yapar Toros, Ayla Yenigün, ve Mustafa Ertek. “Antibiyotik kullanımı Ve Altta Yatan hastalıklar çoklu Ilaca dirençli Toplum kökenli pnömoni Riskini Ve Mortaliteyi artırıyor Mu?”. Pamukkale Medical Journal 15, sy. 2 (Nisan 2022): 229-37. https://doi.org/10.31362/patd.967856.
EndNote Mert D, Öksüzoğlu H, İskender G, Yapar Toros G, Yenigün A, Ertek M (01 Nisan 2022) Antibiyotik kullanımı ve altta yatan hastalıklar çoklu ilaca dirençli toplum kökenli pnömoni riskini ve mortaliteyi artırıyor mu?. Pamukkale Medical Journal 15 2 229–237.
IEEE D. Mert, H. Öksüzoğlu, G. İskender, G. Yapar Toros, A. Yenigün, ve M. Ertek, “Antibiyotik kullanımı ve altta yatan hastalıklar çoklu ilaca dirençli toplum kökenli pnömoni riskini ve mortaliteyi artırıyor mu?”, Pam Tıp Derg, c. 15, sy. 2, ss. 229–237, 2022, doi: 10.31362/patd.967856.
ISNAD Mert, Duygu vd. “Antibiyotik kullanımı Ve Altta Yatan hastalıklar çoklu Ilaca dirençli Toplum kökenli pnömoni Riskini Ve Mortaliteyi artırıyor Mu?”. Pamukkale Medical Journal 15/2 (Nisan 2022), 229-237. https://doi.org/10.31362/patd.967856.
JAMA Mert D, Öksüzoğlu H, İskender G, Yapar Toros G, Yenigün A, Ertek M. Antibiyotik kullanımı ve altta yatan hastalıklar çoklu ilaca dirençli toplum kökenli pnömoni riskini ve mortaliteyi artırıyor mu?. Pam Tıp Derg. 2022;15:229–237.
MLA Mert, Duygu vd. “Antibiyotik kullanımı Ve Altta Yatan hastalıklar çoklu Ilaca dirençli Toplum kökenli pnömoni Riskini Ve Mortaliteyi artırıyor Mu?”. Pamukkale Medical Journal, c. 15, sy. 2, 2022, ss. 229-37, doi:10.31362/patd.967856.
Vancouver Mert D, Öksüzoğlu H, İskender G, Yapar Toros G, Yenigün A, Ertek M. Antibiyotik kullanımı ve altta yatan hastalıklar çoklu ilaca dirençli toplum kökenli pnömoni riskini ve mortaliteyi artırıyor mu?. Pam Tıp Derg. 2022;15(2):229-37.
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