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Rheumatoid Arthritis – Is There a Role for Apitherapy? Analysis of Books Written by Apitherapists Shows that Most Recommendations are Not Evidence-Based

Yıl 2022, , 103 - 118, 31.12.2022
https://doi.org/10.35206/jan.1045529

Öz

Apitherapy is a therapeutic approach based on the use of beehive products. It is frequently suggested for the treatment of rheumatoid arthritis. This study was to assess the recommendations of apitherapists regarding the treatment of rheumatoid arthritis. 129 books written by apitherapists were reviewed regarding their recommendations for rheumatoid arthritis. These recommendations were compared to the findings of preclinical and clinical studies on the subject. Sixty-eight (52.7%) of the books mention the topic of rheumatoid arthritis and there were 44 different recommendations. They include all bee products (honey, pollen, propolis, etc.) but mainly bee venom (15 times) and royal jelly (5 times). Bee venom acupuncture (apipuncture) is mentioned only once. Compared to analyses from the scientific literature, only bee venom but mainly apipuncture are supported. This analysis shows that the majority of apitherapeutic books do not provide adequate information. However, some reports supported the scientific evidence that bee venom and apipuncture could be an interesting means of treatment of rheumatoid arthritis but more and higher quality clinical investigations are necessary.

Destekleyen Kurum

none

Proje Numarası

-

Teşekkür

-

Kaynakça

  • Abdel-Rahman, M., Elebiary, A. S., Hafez, S. S., Mohammed, H. E., Abdel –Moneim, A. E (2013). Therapeutic activity of BEE-stings therapy in rheumatoid arthritis causes inflammation and oxidative stress in female patients. International Journal of Research in Ayurveda and Pharmacy, 4, 316-321.
  • Abdulsalam, M. A., Ebrahim, B. E., & Abdulsalam, A. J. (2016). Immune thrombocytopenia after bee venom therapy: a case report. BMC Complementary and Alternative Medicine, 6, 107.
  • Aletaha, D., Neogi, T., Silman, A. J., Funovits, J., Felson, D. T., Bingham, C. O., ……………….& Hawker, G. (2010). Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis & Rheumatology, 62, 2569-2581.
  • Alqutub, A. N., Masoodi, I., Alsayari, K., & Alomair, A. (2011). Bee sting therapy-induced hepatotoxicity: a case report. World Journal of Hepatology, 3, 268-270.
  • Bhalerao, M. S., Bolshete, P. M., Swar, B. D., Bangera, T. A., Kolhe, V. R., Tambe, M. J., Wade, M. P., Bhowate, S. D., Sonje, U. B., Gogtay, N. J., & Thatte, U. M. (2013). Use of and satisfaction with complementary and alternative medicine in four chronic diseases: a cross-sectional study from India. National Medical Journal of India, 26, 75-78.
  • Cao, H., Yang, G., Wang, Y., Liu, J. P., Smith, C. A., Luo, H., & Liu, Y. (2005). Complementary therapies for acne vulgaris. Cochrane Database of Systematic Reviews, 1, CD009436. Chen, J., & Lariviere, W. R. (2010). The nociceptive and anti-nociceptive effects of bee venom injection and therapy: a double-edged sword. Progress in Neurobiology, 92, 151-183.
  • Chen, S. Y., Zhou, P., & Qin, Y. (2018). Treatment of rheumatoid arthritis by bee-venom acupuncture. Zhen Ci Yan Jiu, 43: 251-254.
  • Fernández-Llanio Comella, N., Fernández Matilla, M., & Castellano Cuesta, J. A. (2016) Have complementary therapies demonstrated effectiveness in rheumatoid arthritis? Reumatología Clínica, 12, 151-157.
  • Fiehn, C., Holle, J., Iking-Konert, C., Leipe, J., Weseloh, C., Frerix, M., Alten, R., Behrens, F., Baerwald, C., Braun, J., Burkhardt, H., Burmester, G., Detert, J., Gaubitz, M., Gause, A., Gromnica-Ihle, E., Kellner, H., Krause, A., Kuipers, J. 0., …….. & Krüger, K. (2018) S2e-Leitlinie: Therapie der rheumatoiden Arthritis mit krankheitsmodifizierenden Medikamenten. [S2e guideline: treatment of rheumatoid arthritis with disease-modifying drugs]. Zeitschrift für Rheumatologie, 77(Suppl 2), 35-53.
  • Hainbuch, F. (2016). Bienengiftbuch – Akupunktur mit Bienengift und Bienenstichen Leipzig. (Einbuch).
  • Institute for Quality and Efficiency in Health Care. Systematic guideline search and appraisal, as well as extraction of relevant recommendations, for a DMP "Chronic Back Pain" [Internet]. Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG); 2015 Nov. Extract of Final Report No. V14-04.
  • Jagua-Gualdrón, A., Peña-Latorre, J. A., & Fernadez-Bernal, R. E. (2020). Apitherapy for osteoarthritis: perspectives from basic research. Complementary Medicine Research, 27, 184-192.
  • Jo, N., & Roh, J. (2015). Systemic immediate hypersensitive reactions after treatment with sweet bee venom: a case report. Journal of Pharmacopuncture, 18, 59-62. Kumar, G., Srivastava, A., Sharma, S. K., Rao, T. D., & Gupta, Y. K. (2015). Efficacy & safety evaluation of Ayurvedic treatment (Ashwagandha powder & Sidh Makardhwaj) in rheumatoid arthritis patients: a pilot prospective study. Indian Journal of Medical Research, 141, 100-106.
  • Lee, H. J., Park, I. S., Lee, J. I., & Kim, J. S. (2015). Guillain-Barré syndrome following bee venom acupuncture. Internal Medicine, 54, 975-978.
  • Lee, J. A., Son, M. J., Choi, J., Jun, J. H., Kim, J. I., & Lee, M. S. (2014). Bee venom acupuncture for rheumatoid arthritis: a systematic review of randomised clinical trials. BMJ Open, 4, e006140.
  • Lee, M. S., Lee, M. S., Yang, C. Y., Lee, S. I., Joo, M. C., Shin, B. C., Yoo, W. H., & Shin, Y. I. (2008). Use of complementary and alternative medicine by rheumatoid arthritis patients in Korea. Clinical Rheumatology, 27, 29-33.
  • Lee, M. S., Pittler, M. H., Shin, B. C., Kong, J. C., & Ernst, E. (2008). Bee venom acupuncture for musculoskeletal pain: a review. Journal of Pain, 8, 289-297.
  • Lim, S. M., & Lee, S. H. (2015). Effectiveness of bee venom acupuncture in alleviating post-stroke shoulder pain: a systematic review and meta-analysis. Journal of Integrative Medicine, 13(4), 241-247.
  • Littlejohn, E. A., & Monrad, S. U. (2018). Early diagnosis and treatment of rheumatoid arthritis. Primary Care, 45, 237-255.
  • Liu, X. D., Zhang, J. L., Zheng, H. G., Liu, F. Y., & Chen, Y. (2008). Clinical randomized study of bee-sting therapy for rheumatoid arthritis. Zhen Ci Yan Jiu, 33(3), 197-200.
  • Lopes-Júnior, C. L., Cruz, L. A., Leopoldo, V. C., Campos, F. R., Almeida, A. M., & Silveira, R. C. (2016). Effectiveness of Traditional Chinese Acupuncture versus sham acupuncture: a systematic review. Revista Latino-Americana de Enfermagem, 24, e2762.
  • Park, J. H., Yim, B. K., Lee, J. H., Lee, S., & Kim, T. H. (2015). Risk associated with bee venom therapy: a systematic review and meta-analysis. PLoS One, 10, e0126971.
  • Park, J. S., Park, Y. G., Jang, C. H., Cho, Y. N., & Park, J. H. (2017). Severe ulnar nerve injury after bee venom acupuncture at a Traditional Korean Medicine clinic: a case report. Annals of Rehabilitation Medicine, 41, 483-487.
  • Phang, J. K., Kwan, Y. H., Goh, H., Tan, V. I. C., Thumboo, J., Østbye, T., & Fong, W. (2018) Complementary and alternative medicine for rheumatic diseases: A systematic review of randomized controlled trials. Complementary Therapies in Medicine, 37, 143-157.
  • Shin, B.-C., Kong, J. C., Park, T. Y., Yang, C. Y., Kang, K. W., Choi, S. (2014). Bee venom acupuncture for chronic low back pain: A randomised, sham-controlled, triple-blind clinical trial. European Journal of Integrative Medicine, 4, e271-e280.
  • Steigerwaldt, F., Mathies, H., & Damrau, F. (1966) Standardized bee venom (SBV) therapy of arthritis. Controlled study of 50 cases with 84 percent benefit. Industrial Medicine and Surgery, 35, 1045-1049.
  • Tekeoglu, I., Akdogan, M., & Kaleli, S. (2016). Bee venom apipuncture; a successful therapy for myofascial pain. A case based review. Journal of Apitherapy, 1,20-22.
  • Terč, F. (1888). Ueber eine merkwuerdige Beziehung des Bienenstiches zum Rheumatismus. Wiener medizinische Presse, 35, 1261-1264.
  • Tertsch, R. (1912). Das Bienengift im Dienste der Medizin. Wien (Österreichischer Reichsverein für Bienenzucht - independently published).
  • Tokem, Y., Parlar Kilic, S., Ozer, S., Nakas, D., & Argon, G. (2014). A multicenter analysis of the use of complementary and alternative medicine in Turkish patients with rheumatoid arthritis: holistic nursing practice review copy. Holistic Nursing Practice, 28, 98-105.
  • Yamasaki, S. C., Mendes, M. T., Alponti, R. F., & Silveira, P. F. (2015). Efficacy of parenteral administration of bee venom in experimental arthritis in the rat: a comparison with methotrexate. Toxicon, 98, 75-88.
  • Zhang, S., Liu, Y., Ye, Y., Wang, X. R., Lin, L. T., Xiao, L. Y., Zhou, P., Shi, G.X., & Liu, C. Z. (2018). Bee venom therapy: potential mechanisms and therapeutic applications. Toxicon, 148, 64-73.
  • Zhang, L. L., Chu, Q., Wang, S., Lai, H., & Xie, B. B. (2016). Is sham acupuncture as effective as traditional Chinese acupuncture? It's too early to say. Chinese Journal of Integrative Medicine, 22, 483-489.
  • Zhao, M., Bai, J., Lu, Y., Du, S., Shang, K., Li, P., Yang, L., Dong, B., & Tan, N. (2016). Anti-arthritic effects of microneedling with bee venom gel. Journal of Traditional Chinese Medical Sciences, 3, 256e262.

Romatoid Artrit – Apiterapinin Rolü Var mı? Apiterapistler Tarafından Yazılmış Kitapların Analizi, Önerilerin Çoğunun Kanıta Dayalı Olmadığını Gösteriyor

Yıl 2022, , 103 - 118, 31.12.2022
https://doi.org/10.35206/jan.1045529

Öz

Apiterapi, arı kovanı ürünlerinin kullanımına dayalı bir tedavi yaklaşımıdır. Romatoid artrit tedavisi için sıklıkla önerilmektedir. Bu çalışma, apiterapistlerin romatoid artrit tedavisine ilişkin önerilerini değerlendirmek amacıyla yapılmıştır. Apiterapistler tarafından yazılan 129 kitap, romatoid artrit önerileri açısından gözden geçirilmiştir. Bu öneriler, konuyla ilgili klinik öncesi ve klinik çalışmaların bulgularıyla karşılaştırılmıştır. Kitapların 68'i (%52.7) romatoid artrit konusuna değinmektedir ve 44 farklı öneri bulunmaktadır. Bu öneriler tüm arı ürünlerini (bal, polen, propolis vb.) içermekle birlikte başlıca arı zehiri (15 kez) ve arı sütüne (5 kez) değinilmiştir. Arı zehri akupunkturundan (apipunktur) sadece bir kez bahsedilmiştir. Bilimsel literatürdeki analizlerle karşılaştırıldığında, sadece arı zehri ancak ağırlıklı olarak apipunktur desteklenmektedir. Bu analiz, apiterapötik kitapların çoğunun yeterli bilgi sağlamadığını göstermektedir. Bazı araştırmalar arı zehri ve apipunkturun romatoid artrit tedavisine yönelik farklı bir tedavi yaklaşımı olabileceğine yönelik bilimsel kanıtları desteklemekte olup bununla birlikte bu konuda daha fazla ve daha kaliteli klinik araştırmalara ihiyaç vardır.

Proje Numarası

-

Kaynakça

  • Abdel-Rahman, M., Elebiary, A. S., Hafez, S. S., Mohammed, H. E., Abdel –Moneim, A. E (2013). Therapeutic activity of BEE-stings therapy in rheumatoid arthritis causes inflammation and oxidative stress in female patients. International Journal of Research in Ayurveda and Pharmacy, 4, 316-321.
  • Abdulsalam, M. A., Ebrahim, B. E., & Abdulsalam, A. J. (2016). Immune thrombocytopenia after bee venom therapy: a case report. BMC Complementary and Alternative Medicine, 6, 107.
  • Aletaha, D., Neogi, T., Silman, A. J., Funovits, J., Felson, D. T., Bingham, C. O., ……………….& Hawker, G. (2010). Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis & Rheumatology, 62, 2569-2581.
  • Alqutub, A. N., Masoodi, I., Alsayari, K., & Alomair, A. (2011). Bee sting therapy-induced hepatotoxicity: a case report. World Journal of Hepatology, 3, 268-270.
  • Bhalerao, M. S., Bolshete, P. M., Swar, B. D., Bangera, T. A., Kolhe, V. R., Tambe, M. J., Wade, M. P., Bhowate, S. D., Sonje, U. B., Gogtay, N. J., & Thatte, U. M. (2013). Use of and satisfaction with complementary and alternative medicine in four chronic diseases: a cross-sectional study from India. National Medical Journal of India, 26, 75-78.
  • Cao, H., Yang, G., Wang, Y., Liu, J. P., Smith, C. A., Luo, H., & Liu, Y. (2005). Complementary therapies for acne vulgaris. Cochrane Database of Systematic Reviews, 1, CD009436. Chen, J., & Lariviere, W. R. (2010). The nociceptive and anti-nociceptive effects of bee venom injection and therapy: a double-edged sword. Progress in Neurobiology, 92, 151-183.
  • Chen, S. Y., Zhou, P., & Qin, Y. (2018). Treatment of rheumatoid arthritis by bee-venom acupuncture. Zhen Ci Yan Jiu, 43: 251-254.
  • Fernández-Llanio Comella, N., Fernández Matilla, M., & Castellano Cuesta, J. A. (2016) Have complementary therapies demonstrated effectiveness in rheumatoid arthritis? Reumatología Clínica, 12, 151-157.
  • Fiehn, C., Holle, J., Iking-Konert, C., Leipe, J., Weseloh, C., Frerix, M., Alten, R., Behrens, F., Baerwald, C., Braun, J., Burkhardt, H., Burmester, G., Detert, J., Gaubitz, M., Gause, A., Gromnica-Ihle, E., Kellner, H., Krause, A., Kuipers, J. 0., …….. & Krüger, K. (2018) S2e-Leitlinie: Therapie der rheumatoiden Arthritis mit krankheitsmodifizierenden Medikamenten. [S2e guideline: treatment of rheumatoid arthritis with disease-modifying drugs]. Zeitschrift für Rheumatologie, 77(Suppl 2), 35-53.
  • Hainbuch, F. (2016). Bienengiftbuch – Akupunktur mit Bienengift und Bienenstichen Leipzig. (Einbuch).
  • Institute for Quality and Efficiency in Health Care. Systematic guideline search and appraisal, as well as extraction of relevant recommendations, for a DMP "Chronic Back Pain" [Internet]. Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG); 2015 Nov. Extract of Final Report No. V14-04.
  • Jagua-Gualdrón, A., Peña-Latorre, J. A., & Fernadez-Bernal, R. E. (2020). Apitherapy for osteoarthritis: perspectives from basic research. Complementary Medicine Research, 27, 184-192.
  • Jo, N., & Roh, J. (2015). Systemic immediate hypersensitive reactions after treatment with sweet bee venom: a case report. Journal of Pharmacopuncture, 18, 59-62. Kumar, G., Srivastava, A., Sharma, S. K., Rao, T. D., & Gupta, Y. K. (2015). Efficacy & safety evaluation of Ayurvedic treatment (Ashwagandha powder & Sidh Makardhwaj) in rheumatoid arthritis patients: a pilot prospective study. Indian Journal of Medical Research, 141, 100-106.
  • Lee, H. J., Park, I. S., Lee, J. I., & Kim, J. S. (2015). Guillain-Barré syndrome following bee venom acupuncture. Internal Medicine, 54, 975-978.
  • Lee, J. A., Son, M. J., Choi, J., Jun, J. H., Kim, J. I., & Lee, M. S. (2014). Bee venom acupuncture for rheumatoid arthritis: a systematic review of randomised clinical trials. BMJ Open, 4, e006140.
  • Lee, M. S., Lee, M. S., Yang, C. Y., Lee, S. I., Joo, M. C., Shin, B. C., Yoo, W. H., & Shin, Y. I. (2008). Use of complementary and alternative medicine by rheumatoid arthritis patients in Korea. Clinical Rheumatology, 27, 29-33.
  • Lee, M. S., Pittler, M. H., Shin, B. C., Kong, J. C., & Ernst, E. (2008). Bee venom acupuncture for musculoskeletal pain: a review. Journal of Pain, 8, 289-297.
  • Lim, S. M., & Lee, S. H. (2015). Effectiveness of bee venom acupuncture in alleviating post-stroke shoulder pain: a systematic review and meta-analysis. Journal of Integrative Medicine, 13(4), 241-247.
  • Littlejohn, E. A., & Monrad, S. U. (2018). Early diagnosis and treatment of rheumatoid arthritis. Primary Care, 45, 237-255.
  • Liu, X. D., Zhang, J. L., Zheng, H. G., Liu, F. Y., & Chen, Y. (2008). Clinical randomized study of bee-sting therapy for rheumatoid arthritis. Zhen Ci Yan Jiu, 33(3), 197-200.
  • Lopes-Júnior, C. L., Cruz, L. A., Leopoldo, V. C., Campos, F. R., Almeida, A. M., & Silveira, R. C. (2016). Effectiveness of Traditional Chinese Acupuncture versus sham acupuncture: a systematic review. Revista Latino-Americana de Enfermagem, 24, e2762.
  • Park, J. H., Yim, B. K., Lee, J. H., Lee, S., & Kim, T. H. (2015). Risk associated with bee venom therapy: a systematic review and meta-analysis. PLoS One, 10, e0126971.
  • Park, J. S., Park, Y. G., Jang, C. H., Cho, Y. N., & Park, J. H. (2017). Severe ulnar nerve injury after bee venom acupuncture at a Traditional Korean Medicine clinic: a case report. Annals of Rehabilitation Medicine, 41, 483-487.
  • Phang, J. K., Kwan, Y. H., Goh, H., Tan, V. I. C., Thumboo, J., Østbye, T., & Fong, W. (2018) Complementary and alternative medicine for rheumatic diseases: A systematic review of randomized controlled trials. Complementary Therapies in Medicine, 37, 143-157.
  • Shin, B.-C., Kong, J. C., Park, T. Y., Yang, C. Y., Kang, K. W., Choi, S. (2014). Bee venom acupuncture for chronic low back pain: A randomised, sham-controlled, triple-blind clinical trial. European Journal of Integrative Medicine, 4, e271-e280.
  • Steigerwaldt, F., Mathies, H., & Damrau, F. (1966) Standardized bee venom (SBV) therapy of arthritis. Controlled study of 50 cases with 84 percent benefit. Industrial Medicine and Surgery, 35, 1045-1049.
  • Tekeoglu, I., Akdogan, M., & Kaleli, S. (2016). Bee venom apipuncture; a successful therapy for myofascial pain. A case based review. Journal of Apitherapy, 1,20-22.
  • Terč, F. (1888). Ueber eine merkwuerdige Beziehung des Bienenstiches zum Rheumatismus. Wiener medizinische Presse, 35, 1261-1264.
  • Tertsch, R. (1912). Das Bienengift im Dienste der Medizin. Wien (Österreichischer Reichsverein für Bienenzucht - independently published).
  • Tokem, Y., Parlar Kilic, S., Ozer, S., Nakas, D., & Argon, G. (2014). A multicenter analysis of the use of complementary and alternative medicine in Turkish patients with rheumatoid arthritis: holistic nursing practice review copy. Holistic Nursing Practice, 28, 98-105.
  • Yamasaki, S. C., Mendes, M. T., Alponti, R. F., & Silveira, P. F. (2015). Efficacy of parenteral administration of bee venom in experimental arthritis in the rat: a comparison with methotrexate. Toxicon, 98, 75-88.
  • Zhang, S., Liu, Y., Ye, Y., Wang, X. R., Lin, L. T., Xiao, L. Y., Zhou, P., Shi, G.X., & Liu, C. Z. (2018). Bee venom therapy: potential mechanisms and therapeutic applications. Toxicon, 148, 64-73.
  • Zhang, L. L., Chu, Q., Wang, S., Lai, H., & Xie, B. B. (2016). Is sham acupuncture as effective as traditional Chinese acupuncture? It's too early to say. Chinese Journal of Integrative Medicine, 22, 483-489.
  • Zhao, M., Bai, J., Lu, Y., Du, S., Shang, K., Li, P., Yang, L., Dong, B., & Tan, N. (2016). Anti-arthritic effects of microneedling with bee venom gel. Journal of Traditional Chinese Medical Sciences, 3, 256e262.
Toplam 34 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Bölüm Derleme Makaleleri
Yazarlar

Karsten Münstedt 0000-0003-4273-5964

Proje Numarası -
Yayımlanma Tarihi 31 Aralık 2022
Yayımlandığı Sayı Yıl 2022

Kaynak Göster

APA Münstedt, K. (2022). Rheumatoid Arthritis – Is There a Role for Apitherapy? Analysis of Books Written by Apitherapists Shows that Most Recommendations are Not Evidence-Based. Journal of Apitherapy and Nature, 5(2), 103-118. https://doi.org/10.35206/jan.1045529
AMA Münstedt K. Rheumatoid Arthritis – Is There a Role for Apitherapy? Analysis of Books Written by Apitherapists Shows that Most Recommendations are Not Evidence-Based. J.Apit.Nat. Aralık 2022;5(2):103-118. doi:10.35206/jan.1045529
Chicago Münstedt, Karsten. “Rheumatoid Arthritis – Is There a Role for Apitherapy? Analysis of Books Written by Apitherapists Shows That Most Recommendations Are Not Evidence-Based”. Journal of Apitherapy and Nature 5, sy. 2 (Aralık 2022): 103-18. https://doi.org/10.35206/jan.1045529.
EndNote Münstedt K (01 Aralık 2022) Rheumatoid Arthritis – Is There a Role for Apitherapy? Analysis of Books Written by Apitherapists Shows that Most Recommendations are Not Evidence-Based. Journal of Apitherapy and Nature 5 2 103–118.
IEEE K. Münstedt, “Rheumatoid Arthritis – Is There a Role for Apitherapy? Analysis of Books Written by Apitherapists Shows that Most Recommendations are Not Evidence-Based”, J.Apit.Nat., c. 5, sy. 2, ss. 103–118, 2022, doi: 10.35206/jan.1045529.
ISNAD Münstedt, Karsten. “Rheumatoid Arthritis – Is There a Role for Apitherapy? Analysis of Books Written by Apitherapists Shows That Most Recommendations Are Not Evidence-Based”. Journal of Apitherapy and Nature 5/2 (Aralık 2022), 103-118. https://doi.org/10.35206/jan.1045529.
JAMA Münstedt K. Rheumatoid Arthritis – Is There a Role for Apitherapy? Analysis of Books Written by Apitherapists Shows that Most Recommendations are Not Evidence-Based. J.Apit.Nat. 2022;5:103–118.
MLA Münstedt, Karsten. “Rheumatoid Arthritis – Is There a Role for Apitherapy? Analysis of Books Written by Apitherapists Shows That Most Recommendations Are Not Evidence-Based”. Journal of Apitherapy and Nature, c. 5, sy. 2, 2022, ss. 103-18, doi:10.35206/jan.1045529.
Vancouver Münstedt K. Rheumatoid Arthritis – Is There a Role for Apitherapy? Analysis of Books Written by Apitherapists Shows that Most Recommendations are Not Evidence-Based. J.Apit.Nat. 2022;5(2):103-18.
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