1.Effects of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition Criteria Changes for Schizophrenia on Diagnoses of First-Episode Schizophrenia Spectrum Disorders
WooRi CHO ; Sung-Wan KIM ; Seung-Hee WON ; Bong-Ju LEE ; Naohisa TSUJINO ; Youji TAKUBO ; Taiju YAMAGUCHI ; Takahiro NEMOTO ; Ling LI ; Thi-Hung LE ; Fatima Zahra RAMI ; Young-Chul CHUNG
Psychiatry Investigation 2025;22(2):212-217
		                        		
		                        			 Objective:
		                        			Impact of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) changes on the criteria for schizophrenia (SZ) has been reported to be minimal in previous studies. However, this could be different in first-episode schizophrenia spectrum disorders (FE-SSDs). We investigated what proportion of patients with FE-SSDs was diagnosed based on the sole presence of bizarre delusions (BDs) or first rank auditory hallucinations (FRAHs). Their alternative diagnosis by the DSM-5 was established and diagnostic stability over 1-year was identified. 
		                        		
		                        			Methods:
		                        			This was a retrospective review study on the medical records, case report forms for the subjects with FE-SSDs (n=404) participated in the Korea Early Psychosis Study. The two Japanese sites reviewed retrospectively only medical records of the subjects with FE-SSDs (n=103). We used three different definitions of BDs (strict, narrow, and broad) and specified subtypes of Other Specified Schizophrenia spectrum and Other psychotic disorders (OSSOs). To ensure inter-rater reliability between the hospitals, regular zoom meetings were held. 
		                        		
		                        			Results:
		                        			Forty (7.89%) subjects out of 507 were found to be diagnosed as SSDs based on the sole presence of BDs or FRAHs. All these patients met the criteria of OSSOs and were classified as having pure delusion (n=22), delusion with attenuated auditory hallucinations (AHs) (n=5), pure AHs (n=3) and AHs with attenuated delusion (n=10). The patients with first and second subtypes (n=27) were found to have BDs. The BDs fulfilled mostly strict definitions or satisfied the next broadest definition. The diagnostic stability of FE-OSSOs and its subgroups (first and second subtypes) over 1-year was substantially high (70.27% and 84% respectively). 
		                        		
		                        			Conclusion
		                        			These findings suggest that more rigorous diagnostic assessment should be performed especially to differentiate OSSOs from SZ in patients with FE-SSDs and more refined classification of the subtypes for OSSOs considered in the next DSM revision. 
		                        		
		                        		
		                        		
		                        	
2.Effects of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition Criteria Changes for Schizophrenia on Diagnoses of First-Episode Schizophrenia Spectrum Disorders
WooRi CHO ; Sung-Wan KIM ; Seung-Hee WON ; Bong-Ju LEE ; Naohisa TSUJINO ; Youji TAKUBO ; Taiju YAMAGUCHI ; Takahiro NEMOTO ; Ling LI ; Thi-Hung LE ; Fatima Zahra RAMI ; Young-Chul CHUNG
Psychiatry Investigation 2025;22(2):212-217
		                        		
		                        			 Objective:
		                        			Impact of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) changes on the criteria for schizophrenia (SZ) has been reported to be minimal in previous studies. However, this could be different in first-episode schizophrenia spectrum disorders (FE-SSDs). We investigated what proportion of patients with FE-SSDs was diagnosed based on the sole presence of bizarre delusions (BDs) or first rank auditory hallucinations (FRAHs). Their alternative diagnosis by the DSM-5 was established and diagnostic stability over 1-year was identified. 
		                        		
		                        			Methods:
		                        			This was a retrospective review study on the medical records, case report forms for the subjects with FE-SSDs (n=404) participated in the Korea Early Psychosis Study. The two Japanese sites reviewed retrospectively only medical records of the subjects with FE-SSDs (n=103). We used three different definitions of BDs (strict, narrow, and broad) and specified subtypes of Other Specified Schizophrenia spectrum and Other psychotic disorders (OSSOs). To ensure inter-rater reliability between the hospitals, regular zoom meetings were held. 
		                        		
		                        			Results:
		                        			Forty (7.89%) subjects out of 507 were found to be diagnosed as SSDs based on the sole presence of BDs or FRAHs. All these patients met the criteria of OSSOs and were classified as having pure delusion (n=22), delusion with attenuated auditory hallucinations (AHs) (n=5), pure AHs (n=3) and AHs with attenuated delusion (n=10). The patients with first and second subtypes (n=27) were found to have BDs. The BDs fulfilled mostly strict definitions or satisfied the next broadest definition. The diagnostic stability of FE-OSSOs and its subgroups (first and second subtypes) over 1-year was substantially high (70.27% and 84% respectively). 
		                        		
		                        			Conclusion
		                        			These findings suggest that more rigorous diagnostic assessment should be performed especially to differentiate OSSOs from SZ in patients with FE-SSDs and more refined classification of the subtypes for OSSOs considered in the next DSM revision. 
		                        		
		                        		
		                        		
		                        	
3.Effects of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition Criteria Changes for Schizophrenia on Diagnoses of First-Episode Schizophrenia Spectrum Disorders
WooRi CHO ; Sung-Wan KIM ; Seung-Hee WON ; Bong-Ju LEE ; Naohisa TSUJINO ; Youji TAKUBO ; Taiju YAMAGUCHI ; Takahiro NEMOTO ; Ling LI ; Thi-Hung LE ; Fatima Zahra RAMI ; Young-Chul CHUNG
Psychiatry Investigation 2025;22(2):212-217
		                        		
		                        			 Objective:
		                        			Impact of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) changes on the criteria for schizophrenia (SZ) has been reported to be minimal in previous studies. However, this could be different in first-episode schizophrenia spectrum disorders (FE-SSDs). We investigated what proportion of patients with FE-SSDs was diagnosed based on the sole presence of bizarre delusions (BDs) or first rank auditory hallucinations (FRAHs). Their alternative diagnosis by the DSM-5 was established and diagnostic stability over 1-year was identified. 
		                        		
		                        			Methods:
		                        			This was a retrospective review study on the medical records, case report forms for the subjects with FE-SSDs (n=404) participated in the Korea Early Psychosis Study. The two Japanese sites reviewed retrospectively only medical records of the subjects with FE-SSDs (n=103). We used three different definitions of BDs (strict, narrow, and broad) and specified subtypes of Other Specified Schizophrenia spectrum and Other psychotic disorders (OSSOs). To ensure inter-rater reliability between the hospitals, regular zoom meetings were held. 
		                        		
		                        			Results:
		                        			Forty (7.89%) subjects out of 507 were found to be diagnosed as SSDs based on the sole presence of BDs or FRAHs. All these patients met the criteria of OSSOs and were classified as having pure delusion (n=22), delusion with attenuated auditory hallucinations (AHs) (n=5), pure AHs (n=3) and AHs with attenuated delusion (n=10). The patients with first and second subtypes (n=27) were found to have BDs. The BDs fulfilled mostly strict definitions or satisfied the next broadest definition. The diagnostic stability of FE-OSSOs and its subgroups (first and second subtypes) over 1-year was substantially high (70.27% and 84% respectively). 
		                        		
		                        			Conclusion
		                        			These findings suggest that more rigorous diagnostic assessment should be performed especially to differentiate OSSOs from SZ in patients with FE-SSDs and more refined classification of the subtypes for OSSOs considered in the next DSM revision. 
		                        		
		                        		
		                        		
		                        	
4.Effects of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition Criteria Changes for Schizophrenia on Diagnoses of First-Episode Schizophrenia Spectrum Disorders
WooRi CHO ; Sung-Wan KIM ; Seung-Hee WON ; Bong-Ju LEE ; Naohisa TSUJINO ; Youji TAKUBO ; Taiju YAMAGUCHI ; Takahiro NEMOTO ; Ling LI ; Thi-Hung LE ; Fatima Zahra RAMI ; Young-Chul CHUNG
Psychiatry Investigation 2025;22(2):212-217
		                        		
		                        			 Objective:
		                        			Impact of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) changes on the criteria for schizophrenia (SZ) has been reported to be minimal in previous studies. However, this could be different in first-episode schizophrenia spectrum disorders (FE-SSDs). We investigated what proportion of patients with FE-SSDs was diagnosed based on the sole presence of bizarre delusions (BDs) or first rank auditory hallucinations (FRAHs). Their alternative diagnosis by the DSM-5 was established and diagnostic stability over 1-year was identified. 
		                        		
		                        			Methods:
		                        			This was a retrospective review study on the medical records, case report forms for the subjects with FE-SSDs (n=404) participated in the Korea Early Psychosis Study. The two Japanese sites reviewed retrospectively only medical records of the subjects with FE-SSDs (n=103). We used three different definitions of BDs (strict, narrow, and broad) and specified subtypes of Other Specified Schizophrenia spectrum and Other psychotic disorders (OSSOs). To ensure inter-rater reliability between the hospitals, regular zoom meetings were held. 
		                        		
		                        			Results:
		                        			Forty (7.89%) subjects out of 507 were found to be diagnosed as SSDs based on the sole presence of BDs or FRAHs. All these patients met the criteria of OSSOs and were classified as having pure delusion (n=22), delusion with attenuated auditory hallucinations (AHs) (n=5), pure AHs (n=3) and AHs with attenuated delusion (n=10). The patients with first and second subtypes (n=27) were found to have BDs. The BDs fulfilled mostly strict definitions or satisfied the next broadest definition. The diagnostic stability of FE-OSSOs and its subgroups (first and second subtypes) over 1-year was substantially high (70.27% and 84% respectively). 
		                        		
		                        			Conclusion
		                        			These findings suggest that more rigorous diagnostic assessment should be performed especially to differentiate OSSOs from SZ in patients with FE-SSDs and more refined classification of the subtypes for OSSOs considered in the next DSM revision. 
		                        		
		                        		
		                        		
		                        	
5.Effects of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition Criteria Changes for Schizophrenia on Diagnoses of First-Episode Schizophrenia Spectrum Disorders
WooRi CHO ; Sung-Wan KIM ; Seung-Hee WON ; Bong-Ju LEE ; Naohisa TSUJINO ; Youji TAKUBO ; Taiju YAMAGUCHI ; Takahiro NEMOTO ; Ling LI ; Thi-Hung LE ; Fatima Zahra RAMI ; Young-Chul CHUNG
Psychiatry Investigation 2025;22(2):212-217
		                        		
		                        			 Objective:
		                        			Impact of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) changes on the criteria for schizophrenia (SZ) has been reported to be minimal in previous studies. However, this could be different in first-episode schizophrenia spectrum disorders (FE-SSDs). We investigated what proportion of patients with FE-SSDs was diagnosed based on the sole presence of bizarre delusions (BDs) or first rank auditory hallucinations (FRAHs). Their alternative diagnosis by the DSM-5 was established and diagnostic stability over 1-year was identified. 
		                        		
		                        			Methods:
		                        			This was a retrospective review study on the medical records, case report forms for the subjects with FE-SSDs (n=404) participated in the Korea Early Psychosis Study. The two Japanese sites reviewed retrospectively only medical records of the subjects with FE-SSDs (n=103). We used three different definitions of BDs (strict, narrow, and broad) and specified subtypes of Other Specified Schizophrenia spectrum and Other psychotic disorders (OSSOs). To ensure inter-rater reliability between the hospitals, regular zoom meetings were held. 
		                        		
		                        			Results:
		                        			Forty (7.89%) subjects out of 507 were found to be diagnosed as SSDs based on the sole presence of BDs or FRAHs. All these patients met the criteria of OSSOs and were classified as having pure delusion (n=22), delusion with attenuated auditory hallucinations (AHs) (n=5), pure AHs (n=3) and AHs with attenuated delusion (n=10). The patients with first and second subtypes (n=27) were found to have BDs. The BDs fulfilled mostly strict definitions or satisfied the next broadest definition. The diagnostic stability of FE-OSSOs and its subgroups (first and second subtypes) over 1-year was substantially high (70.27% and 84% respectively). 
		                        		
		                        			Conclusion
		                        			These findings suggest that more rigorous diagnostic assessment should be performed especially to differentiate OSSOs from SZ in patients with FE-SSDs and more refined classification of the subtypes for OSSOs considered in the next DSM revision. 
		                        		
		                        		
		                        		
		                        	
6.Study Design and Protocol for a Randomized Controlled Trial to Assess Long-Term Efficacy and Safety of a Triple Combination of Ezetimibe, Fenofibrate, and Moderate-Intensity Statin in Patients with Type 2 Diabetes and Modifiable Cardiovascular Risk Factors (ENSEMBLE)
Nam Hoon KIM ; Juneyoung LEE ; Suk CHON ; Jae Myung YU ; In-Kyung JEONG ; Soo LIM ; Won Jun KIM ; Keeho SONG ; Ho Chan CHO ; Hea Min YU ; Kyoung-Ah KIM ; Sang Soo KIM ; Soon Hee LEE ; Chong Hwa KIM ; Soo Heon KWAK ; Yong‐ho LEE ; Choon Hee CHUNG ; Sihoon LEE ; Heung Yong JIN ; Jae Hyuk LEE ; Gwanpyo KOH ; Sang-Yong KIM ; Jaetaek KIM ; Ju Hee LEE ; Tae Nyun KIM ; Hyun Jeong JEON ; Ji Hyun LEE ; Jae-Han JEON ; Hye Jin YOO ; Hee Kyung KIM ; Hyeong-Kyu PARK ; Il Seong NAM-GOONG ; Seongbin HONG ; Chul Woo AHN ; Ji Hee YU ; Jong Heon PARK ; Keun-Gyu PARK ; Chan Ho PARK ; Kyong Hye JOUNG ; Ohk-Hyun RYU ; Keun Yong PARK ; Eun-Gyoung HONG ; Bong-Soo CHA ; Kyu Chang WON ; Yoon-Sok CHUNG ; Sin Gon KIM
Endocrinology and Metabolism 2024;39(5):722-731
		                        		
		                        			 Background:
		                        			Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. 
		                        		
		                        			Methods:
		                        			This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. 
		                        		
		                        			Conclusion
		                        			This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D. 
		                        		
		                        		
		                        		
		                        	
7.Efficacy and Safety of Lurasidone vs. Quetiapine XR in Acutely Psychotic Patients With Schizophrenia in Korea: A Randomized, Double-Blind, Active-Controlled Trial
Se Hyun KIM ; Do-Un JUNG ; Do Hoon KIM ; Jung Sik LEE ; Kyoung-Uk LEE ; Seunghee WON ; Bong Ju LEE ; Sung-Gon KIM ; Sungwon ROH ; Jong-Ik PARK ; Minah KIM ; Sung Won JUNG ; Hong Seok OH ; Han-yong JUNG ; Sang Hoon KIM ; Hyun Seung CHEE ; Jong-Woo PAIK ; Kyu Young LEE ; Soo In KIM ; Seung-Hwan LEE ; Eun-Jin CHEON ; Hye-Geum KIM ; Heon-Jeong LEE ; In Won CHUNG ; Joonho CHOI ; Min-Hyuk KIM ; Seong-Jin CHO ; HyunChul YOUN ; Jhin-Goo CHANG ; Hoo Rim SONG ; Euitae KIM ; Won-Hyoung KIM ; Chul Eung KIM ; Doo-Heum PARK ; Byung-Ook LEE ; Jungsun LEE ; Seung-Yup LEE ; Nuree KANG ; Hee Yeon JUNG
Psychiatry Investigation 2024;21(7):762-771
		                        		
		                        			 Objective:
		                        			This study was performed to evaluate the efficacy and safety of lurasidone (160 mg/day) compared to quetiapine XR (QXR; 600 mg/day) in the treatment of acutely psychotic patients with schizophrenia. 
		                        		
		                        			Methods:
		                        			Patients were randomly assigned to 6 weeks of double-blind treatment with lurasidone 160 mg/day (n=105) or QXR 600 mg/day (n=105). Primary efficacy measure was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions severity (CGI-S) score. Adverse events, body measurements, and laboratory parameters were assessed. 
		                        		
		                        			Results:
		                        			Lurasidone demonstrated non-inferiority to QXR on the PANSS total score. Adjusted mean±standard error change at week 6 on the PANSS total score was -26.42±2.02 and -27.33±2.01 in the lurasidone and QXR group, respectively. The mean difference score was -0.91 (95% confidence interval -6.35–4.53). The lurasidone group showed a greater reduction in PANSS total and negative subscale on week 1 and a greater reduction in end-point CGI-S score compared to the QXR group. Body weight, body mass index, and waist circumference in the lurasidone group were reduced, with significantly lower mean change compared to QXR. Endpoint changes in glucose, cholesterol, triglycerides, and low-density lipoprotein levels were also significantly lower. The most common adverse drug reactions with lurasidone were akathisia and nausea. 
		                        		
		                        			Conclusion
		                        			Lurasidone 160 mg/day was found to be non-inferior to QXR 600 mg/day in the treatment of schizophrenia with comparable efficacy and tolerability. Adverse effects of lurasidone were generally tolerable, and beneficial effects on metabolic parameters can be expected. 
		                        		
		                        		
		                        		
		                        	
8.Effectiveness of Switching to Long-acting Injectable Aripiprazole in Patients with Recent-onset and Chronic Schizophrenia
Sung-Wan KIM ; Bong-Ju LEE ; Eun-Jin CHEON ; Seung-Hee WON ; Anna JO ; Jae-Min KIM ; Young-Chul CHUNG
Clinical Psychopharmacology and Neuroscience 2023;21(1):57-67
		                        		
		                        			 Objective:
		                        			This study investigated the effectiveness of switching to once-monthly long-acting injectable (LAI) aripiprazole from other second-generation antipsychotics including LAI paliperidone palmitate in both recent-onset and chronic schizophrenia patients. 
		                        		
		                        			Methods:
		                        			This was a 24-week prospective, open-label, flexible dose-switching study in patients with schizophrenia.  Scores on the Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance (PSP) scale, Clinical Global Impression (CGI), Subjective Well-being Under Neuroleptics−Short Form (SWN-K), and a computerized emotional recognition test (ERT) were evaluated. Subjects were divided into two groups (recent onset and chronic) based on 5 years’ duration of the illness. 
		                        		
		                        			Results:
		                        			Among the 82 patients participating, 67 (81.7%) completed the 24-week study. The discontinuation rate after switching to LAI aripiprazole did not differ according to clinical characteristics including type of previous antipsychotics. Scores on the PANSS, PSP, SWN-K, CGI, and ERT were significantly improved after a switch to LAI aripiprazole without exacerbation of metabolic parameters and bodyweight. The improvements in the PANSS, PSP, and CGI scores were significantly greater in patients with recent-onset than in those with chronic schizophrenia; the improvement in metabolic parameters was significantly greater in the latter group. 
		                        		
		                        			Conclusion
		                        			High rates of successful switching to LAI aripiprazole from other antipsychotics suggest its good tolerability and effectiveness. Improvements in psychopathology and social functioning were more evident in patients with recent-onset schizophrenia, and improvements in metabolic abnormalities were more prominent in patients with chronic schizophrenia. 
		                        		
		                        		
		                        		
		                        	
9.KAAACI Allergic Rhinitis Guidelines: Part 2. Update in nonpharmacotherapy
Sang Chul PARK ; Soo Jie CHUNG ; Jeong-Hee CHOI ; Yong Ju LEE ; Hyeon-Jong YANG ; Do-Yang PARK ; Dong-Kyu KIM ; Il Hwan LEE ; Soo Whan KIM ; Do Hyun KIM ; Young Joon JUN ; Song-I YANG ; Minji KIM ; Gwanghui RYU ; Sung-Yoon KANG ; Sang Min LEE ; Mi-Ae KIM ; Hyun-Jung KIM ; Gil-Soon CHOI ; Hyun Jong LEE ; Hyo-Bin KIM ; Bong-Seong KIM
Allergy, Asthma & Respiratory Disease 2023;11(3):126-134
		                        		
		                        			
		                        			 Allergic rhinitis is the most common chronic disease worldwide. Various upper airway symptoms lower quality of life, and due to the recurrent symptoms, multiple treatments are usually attempted rather than one definitive treatment. There are alternatives to medical (medication-based) and nonmedical treatments. A guideline is needed to understand allergic rhinitis and develop an appropriate treatment plan. We have developed guidelines for medical treatment based on previous reports. The current guidelines herein are associated with the “KAAACI Evidence-Based Guidelines for Allergic Rhinitis in Korea, Part 1: Update in pharmacotherapy” in which we aimed to provide evidence-based recommendations for the medical treatment of allergic rhinitis. Part 2 focuses on nonpharmacological management, including allergen-specific immunotherapy, subcutaneous or sublingual immunotherapy, nasal saline irrigation, environmental management strategies, companion animal management, and nasal turbinate surgery. The evidence to support the treatment efficacy, safety, and selection has been systematically reviewed. However, larger controlled studies are needed to elevate the level of evidence to select rational non-medical therapeutic options for patients with allergic rhinitis. 
		                        		
		                        		
		                        		
		                        	
10.KAAACI Allergic Rhinitis Guidelines: Part 1. Update in pharmacotherapy
Minji KIM ; Sung-Yoon KANG ; Song-I YANG ; Il Hwan LEE ; Gwanghui RYU ; Mi-Ae KIM ; Sang Min LEE ; Hyun-Jung KIM ; Do-Yang PARK ; Yong Ju LEE ; Dong-Kyu KIM ; Do Hyun KIM ; Young Joon JUN ; Sang Chul PARK ; Bong-Seong KIM ; Soojie CHUNG ; Hyun Jong LEE ; Hyo-Bin KIM ; Jeong-Hee CHOI ; Gil-Soon CHOI ; Hyeon-Jong YANG ; Soo Whan KIM
Allergy, Asthma & Respiratory Disease 2023;11(3):117-125
		                        		
		                        			
		                        			 The prevalence of allergic rhinitis (AR) and the socioeconomic burden associated with the medical cost and quality of life of AR have progressively increased. Therefore, practical guidelines for the appropriate management of AR need to be developed based on scientific evidence considering the real-world environment, values, and preferences of patients and physicians. The Korean Academy of Asthma, Allergy and Clinical Immunology revised clinical guidelines for AR to address key clinical questions of the management of AR. Part 1 of the revised guideline covers the pharmacological management of patients with AR in Korea. Through a meta-analysis and a systematic review, we made 4 recommendations for AR pharmacotherapy, including intranasal corticosteroid (INCS)/intranasal antihistamine combination therapy, oral antihistamine/INCS combination therapy, leukotriene receptor antagonist treatment in AR patients with asthma, and prophylactic treatment for patients with pollen-induced AR. However, all recommendations are conditional because of the low or very low evidence of certainty. Well-designed and strictly executed randomized controlled trials are needed to measure and report appropriate outcomes. 
		                        		
		                        		
		                        		
		                        	
            
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