Proliferation of Mouse Prostate Cancer Cells Inflamed by Trichomonas vaginalis

Our objective was to investigate whether inflammatory microenvironment induced by Trichomonas vaginalis infection can stimulate proliferation of prostate cancer (PCa) cells in vitro and in vivo mouse experiments. The production of CXCL1 and CCL2 increased when cells of the mouse PCa cells (TRAMP-C2 cell line) were infected with live T. vaginalis. T. vaginalis-conditioned medium (TCM) prepared from co-culture of PCa cells and T. vaginalis increased PCa cells migration, proliferation and invasion. The cytokine receptors (CXCR2, CCR2, gp130) were expressed higher on the PCa cells treated with TCM. Pretreatment of PCa cells with antibodies to these cytokine receptors significantly reduced the proliferation, mobility and invasiveness of PCa cells, indicating that TCM has its effect through cytokine-cytokine receptor signaling. In C57BL/6 mice, the prostates injected with T. vaginalis mixed PCa cells were larger than those injected with PCa cells alone after 4 weeks. Expression of epithelial-mesenchymal transition markers and cyclin D1 in the prostate tissue injected with T. vaginalis mixed PCa cells increased than those of PCa cells alone. Collectively, it was suggested that inflammatory reactions by T. vaginalis-stimulated PCa cells increase the proliferation and invasion of PCa cells through cytokine-cytokine receptor signaling pathways.

Involvement of Macrophages in Proliferation of Prostate Cancer Cells Infected with Trichomonas vaginalis

Macrophages play a key role in chronic inflammation, and are the most abundant immune cells in the tumor microenvironment. We investigated whether an interaction between inflamed prostate cancer cells stimulated with Trichomonas vaginalis and macrophages stimulates the proliferation of the cancer cells. Conditioned medium was prepared from T. vaginalis-infected (TCM) and uninfected (CM) mouse prostate cancer (PCa) cell line (TRAMP-C2 cells). Thereafter conditioned medium was prepared from macrophages (J774A.1 cell line) after incubation with CM (MCM) or TCM (MTCM). When TRAMP-C2 cells were stimulated with T. vaginalis, protein and mRNA levels of CXCL1 and CCL2 increased, and migration of macrophages toward TCM was more extensive than towards CM. Macrophages stimulated with TCM produced higher levels of CCL2, IL-6, TNF-α, their mRNAs than macrophages stimulated with CM. MTCM stimulated the proliferation and invasiveness of TRAMP-C2 cells as well as the expression of cytokine receptors (CCR2, GP130, CXCR2). Importantly, blocking of each cytokine receptors with anti-cytokine receptor antibody significantly reduced the proliferation and invasiveness of TRAMP-C2 cells. We conclude that inflammatory mediators released by TRAMP-C2 cells in response to infection by T. vaginalis stimulate the migration and activation of macrophages and the activated macrophages stimulate the proliferation and invasiveness of the TRAMP-C2 cells via cytokine-cytokine receptor binding. Our results therefore suggested that macrophages contribute to the exacerbation of PCa due to inflammation of prostate cancer cells reacted with T. vaginalis.

Changes in Prevalence and Treatment Pattern of Benign Prostatic Hyperplasia in Korea / 대한배뇨장애요실금학회지

Purpose@#Benign prostatic hyperplasia (BPH) is associated with lower urinary tract symptoms and negatively affects the quality of life. We aimed to investigate the treatment pattern of BPH in South Korea. @*Methods@#Information on treatment modalities and diagnoses of BPH was obtained from the Health Insurance Review and Assessment Service-Aged Patient Sample. Data on BPH patients aged ≥60 years from 2012 to 2016 were obtained. We surveyed the treatment pattern of BPH, including the types of drugs used and surgeries performed, according to the type of institution. @*Results@#In this study, 18,260–24,657 BPH patients treated between 2012 and 2016 were included. The number of patients showed an increasing pattern, and drug therapy was the major treatment method used for BPH (98.77%). Moreover, the pattern of increased pharmacotherapy use for BPH was reinforced by the increasing number of patients. Prescription of α-blockers only was dominant in this cohort (45.7%). Transurethral resection of the prostate (TURP) was the most commonly used surgical treatment for BPH (53.6%), but it showed a decreasing pattern over time. In contrast, holmium laser enucleation of the prostate (HoLEP) showed an increase from 19.4% to 39.7%. @*Conclusions@#The most common treatment for BPH was drug therapy, predominantly only α-blocker therapy. The surgical treatment trend has changed from TURP to HoLEP.

Catheter-Related Bladder Discomfort: How Can We Manage It? / 대한배뇨장애요실금학회지

The urethral catheter is used in various clinical situations such as diagnosing urologic disease, urine drainage in patients after surgery, and for patients who cannot urinate voluntarily. However, catheters can cause numerous adverse effects, such as catheter-associated infection, obstruction, bladder stones, urethral injury, and catheter-related bladder discomfort (CRBD). CRBD symptoms vary among patients from burning sensation and pain in the suprapubic and penile areas to urinary urgency. CRBD significantly reduces patient quality of life and can lead to several complications. CRBD is caused by catheter-induced bladder irritation due to muscarinic receptor-mediated involuntary contractions of bladder smooth muscle and also can be caused by mechanical stimulus of the urethral catheter. Various pharmacologic studies for managing CRBD, including antimuscarinic and antiepileptic agents and botulinum toxin injections have been reported. If urologists can reduce patients’ CRBD, their quality of life and recovery can improve.

Catheter-Related Bladder Discomfort: How Can We Manage It? / 대한배뇨장애요실금학회지

The urethral catheter is used in various clinical situations such as diagnosing urologic disease, urine drainage in patients after surgery, and for patients who cannot urinate voluntarily. However, catheters can cause numerous adverse effects, such as catheter-associated infection, obstruction, bladder stones, urethral injury, and catheter-related bladder discomfort (CRBD). CRBD symptoms vary among patients from burning sensation and pain in the suprapubic and penile areas to urinary urgency. CRBD significantly reduces patient quality of life and can lead to several complications. CRBD is caused by catheter-induced bladder irritation due to muscarinic receptor-mediated involuntary contractions of bladder smooth muscle and also can be caused by mechanical stimulus of the urethral catheter. Various pharmacologic studies for managing CRBD, including antimuscarinic and antiepileptic agents and botulinum toxin injections have been reported. If urologists can reduce patients’ CRBD, their quality of life and recovery can improve.

Do Lifestyle Factors Affect Lower Urinary Tract Symptoms? Results from the Korean Community Health Survey / 대한배뇨장애요실금학회지

PURPOSE: To evaluate the relationships between lower urinary tract symptoms (LUTS) and lifestyle factors (physical activity, smoking, alcohol consumption, body mass index, and stress) in Korean men. METHODS: We analyzed the survey results of South Korean men (n=64,439) who were 40 years of age or older among whom interviews were conducted using questionnaires. Trained interviewers performed face-to-face surveys using computer-assisted personal interviewing, the International Prostate Symptom Score (IPSS), and standard questions. We assessed the relationships of lifestyle factors (physical activity, cigarette smoking, alcohol intake, height, weight, and stress) with LUTS. RESULTS: We observed higher IPSS scores in participants who engaged in no exercise (n=46,008 [71.7%], IPSS=3.19±5.36) than in those who engaged in vigorous physical activity (n=10,657 [17.6%], IPSS=2.28±4.15). Former smokers showed higher total, storage, and voiding symptom IPSS scores than current smokers and nonsmokers. Nondrinkers had higher IPSS scores than current alcohol drinkers. In multivariable logistic regression analysis, we detected no relationship between LUTS and current alcohol drinking in the moderate and severe LUTS groups, using the mild LUTS group as a reference (moderate: 0.91; 95% confidence interval [CI], 0.91–0.91; P<0.001, severe: 0.78; 95% CI, 0.78–0.78; P<0.001). Participants with moderate to severe stress showed higher total IPSS scores than those with no or mild stress (3.38±5.77 vs. 2.88±4.90), with significant relationships between stress and LUTS found in the moderate and severe LUTS groups. In logistic regression analysis, stronger relationships were found for storage and voiding symptoms in the moderate and severe stress groups compared to the mild stress group. CONCLUSIONS: A history of smoking, low levels of physical activity, low body mass index, and moderate to severe stress were associated with a greater severity of LUTS. Moderate to severe stress was also related to voiding symptoms. However, there was no association between alcohol intake and LUTS severity.

Comparison of Seropositivity to Trichomonas vaginalis between Men with Prostatic Tumor and Normal Men

Trichomoniasis is the most common curable sexually-transmitted infection. Most Trichomonas vaginalis-infected men are asymptomatic and can remain undiagnosed and untreated, and this has been thought to result in chronic persistent prostatic infection. Chronic inflammation is regarded as the major factor in the pathogenesis and progression of benign prostatic hyperplasia (BPH) and prostatic cancer (PCa). The aim of this study is to identify seropositivity to T. vaginalis in men with prostate tumors (BPH or PCa) visited to Hanyang University Hospital. A total of 183 men were enrolled between October 2013 and November 2014. They consisted of 139 with BPH (mean age: 64.0±0.07) and 44 with prostate cancer (mean age: 73.3±0.18). We carried out ELISA to identify the seropositivity to T. vaginalis. Mixed lysate antigen extracted from 8 strains of T. vaginalis was used in the ELISA. Also 58 male outpatients visited to Health Promotion Center in Hanyang University Hospital were evaluated for comparing group. As a results, seropositivity to T. vaginalis in patients with prostatic diseases was 19.7% (BPH: 18.7%, PCa: 22.7%) and it was significantly higher than the 1.7% of the comparing healthy group (P=0.001). Therefore, prostatic tumor showed higher seropositivity against T. vaginalis than normal men. As far as we know, this is the first report about seroprevalence in prostatic tumor in Korea.

Safety and Efficacy of the Coadministration of Sildenafil and Finasteride

PURPOSE: The 5-alpha reductase inhibitors (5ARI) are one of the most commonly used medications for the treatment of benign prostatic hyperplasia (BPH). Phosphodiesterase type-5 inhibitors are also used to treat BPH. 5ARI is a drug with adverse effects of sexual dysfunction. In this study, we investigated the safety and efficacy of coadministration of finasteride and sildenafil on sexual function and lower urinary symptoms in patients with BPH. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients who were receiving finasteride and sildenafil daily regimens for treatment of BPH in 2 university hospitals. Patients with adverse effects, vital sign, physical exam, laboratory test, 5-item version of the international index of erectile function (IIEF-5), International Prostate Symptom Score (IPSS), quality of life (QoL) were analyzed. RESULTS: The number of patients analyzed in this study was 218. The mean age of the patients was 62.63±8.37 years and the mean duration of medication was 18.23±10.97 weeks. Significant changes were not observed in the vital signs measured before and after the drug administration. Compared with before treatment, improvement of lower urinary tract symptom (IPSS: 17.56±4.21 vs. 11.64±5.33, p < 0.001) was observed and improvement of sexual function (IIEF-5: 9.44±5.21 vs. 12.73±6.81, p < 0.001) was also confirmed. CONCLUSIONS: Daily coadministration of finasteride and sildenafil for the treatment of BPH could be used safely, and improvement of lower urinary tract symptom as well as improvement of sexual function could be expected.

Sociodemographic Factors Related to Lower Urinary Tract Symptoms in Men: A Korean Community Health Survey / 대한배뇨장애요실금학회지

PURPOSE: This study estimated the prevalence of lower urinary tract symptoms (LUTS) in Korean men and the conditions for being diagnosed with or treated for LUTS/benign prostatic hyperplasia (BPH). METHODS: We analyzed cross-sectional data collected from 69,851 Korean men who were 40 years of age or older and had participated in the Korean Community Health Survey performed in 2011. Interviewers performed face-to-face surveys that included sociodemographic questions, the International Prostate Symptom Score (IPSS), and questions regarding whether the subjects had been diagnosed with or treated for LUTS/BPH. We estimated the prevalence of LUTS and assessed whether the subjects had been diagnosed with or treated for LUTS/BPH. RESULTS: Moderate to severe LUTS, storage symptoms, and voiding symptoms increased with age. The IPSS quality of life score was 1.5±0.004 in the mild LUTS group (n=57,701), 3.3±0.01 in the moderate LUTS group (n=9,203), and 4.3±0.02 in the severe LUTS group (n=2,947) (P<0.0001). The prevalence of moderate to severe LUTS in those who had not been diagnosed with LUTS/BPH was 64.5% (7,847 of 12,150), and the prevalence of moderate to severe LUTS in those who had been diagnosed with LUTS/BPH but had not been treated was 23.5% (2,853 of 12,150). CONCLUSIONS: The severity of LUTS in Korean men increased with age, and the IPSS quality of life score increased with the severity of LUTS. Many Korean men with moderate to severe LUTS had not been diagnosed or treated for LUTS/BPH. Socioeconomic conditions played an important role in health-seeking behavior among patients with LUTS/BPH.

Antimuscarinic Agent Treatment Affecting Patient-Reported Outcomes in Overactive Bladder Syndrome With Depressive Symptoms / 대한배뇨장애요실금학회지

PURPOSE: We investigated improvements in overactive bladder symptoms and depressive symptoms after solifenacin treatment in overactive bladder patients with or without depressive symptoms. METHODS: We performed a prospective study of patients who had been diagnosed with overactive bladder from July 2013 to June 2014. Based on the Beck Depression Inventory questionnaire, the test subjects were divided into group 1, without depressive symptoms (0–9 points), and group 2, with depressive symptoms (10 or more points). The patients were administered 5 mg of solifenacin for 3 months. The following outcomes were analyzed at the first visit, 4 weeks, and 12 weeks: the overactive bladder symptom score (OABSS), International Prostate Symptom Score (IPSS), patients’ perceptions of their bladder condition, and the Beck Depression Inventory. RESULTS: A total of 72 patients participated, and 52 patients completed the study. Most outcome measures showed improvements in both groups at weeks 4 and 12. Especially in group 2, the questionnaires showed significant improvements from baseline to week 12, indicating that solifenacin was effective at treating overactive bladder symptoms (group 1 vs. group 2: OABSS, −2.67±0.80 vs. −3.00±0.77; P<0.01; IPSS-total, −2.14±2.15 vs. −4.94±1.70; P<0.01). Statistically significant decreases in the Beck Depression Inventory score from baseline to weeks 4 and 12 were observed in group 2 (group 1 vs. group 2: 1.43±0.74 vs. −2.68±4.05 at week 4, P<0.001; 0.10±3.37 vs. −5.52±5.82 at week 12, P<0.001). CONCLUSIONS: In overactive bladder patients with depressive symptoms, solifenacin can help improve quality of life and depressive symptoms at the same time.

The Effect of Two Weeks of Treatment with Dutasteride on Bleeding after Transurethral Resection of the Prostate

PURPOSE: Dutasteride affects the prostate by reducing intraprostatic dihydrotestosterone and prostate tissue vascularity. We evaluated the effect of pretreatment with dutasteride for two weeks on perioperative and postoperative bleeding during transurethral resection of the prostate (TURP). MATERIALS AND METHODS: Eighty-three patients who had benign prostatic hyperplasia together with the criteria for eligibility for TURP were included. The dutasteride group consisted of 40 patients who were treated with dutasteride (0.5 mg/d) for two weeks before surgery, and the control group consisted of 43 patients who did not receive dutasteride. Blood loss was evaluated in terms of reduction in serum hemoglobin (Hb) and hematocrit (Hct) levels, which were measured before, immediately after, and 24 hours after surgery. We also measured the durations of indwelling urethral catheter use, continuous saline bladder irrigation, and hospitalization. RESULTS: Lower mean blood loss was observed in the dutasteride group than the control group immediately after and 24 hours after surgery (DeltaHb=0.65+/-1.27 g/dL vs. 1.16+/-0.73 g/dL, 1.30+/-1.00 g/dL vs. 1.86+/-1.05 g/dL respectively, p=0.019, p=0.011; DeltaHct=1.89%+/-3.83% vs. 3.47%+/-2.09%, 3.69%+/-2.95% vs. 5.39%+/-3.23% respectively, p=0.016, p=0.011). In addition, there were fewer days of indwelling urethral catheter use (2.95+/-1.02 d vs. 3.92+/-1.14 d, p=0.000), continuous saline bladder irrigation (1.81+/-1.08 d vs. 2.36+/-1.06 d, p=0.016), and hospitalization after TURP (3.95+/-1.09 d vs. 4.76+/-1.19 d, p=0.001) in the dutasteride group. CONCLUSIONS: Preoperative treatment with dutasteride for two weeks before TURP reduces surgical bleeding and length of hospitalization after TURP. This pretreatment can be used to decrease surgical bleeding associated with TURP.

Comparison of Erectile Dysfunction Treatment Efficacy of Mirodenalfil 50mg Once Daily and 100mg On-Demand in Patients with Benign Prostatic Hyperplasia and Erectile Dysfunction: Multicenter, Randomized

PURPOSE: To Compare the improvement of erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) as well as the efficacy of mirodenalfil 50mg once daily and 100mg on-demand in patients with benign prostatic hyperplasia (BPH) and erectile dysfunction (ED). MATERIALS AND METHODS: Prospective study was done with 220 patients who had BPH and ED from June 2013 to October 2014. Out of 220 individuals, 260 met inclusion criteria and 204 finished the research. Patients were divided into two groups. Group 1 had mirodenafil 50mg once daily and Group 2 had mirodenafil 100mg on-demand. The five-item version of the International Index of Erectile Function (IIEF-5), International Prostate Symptom Score (IPSS), Qmax, and residual urine volume(PVR) were assessed immediately before initiation of treatment (V1) and after four (V2) and twelve weeks of treatment (V3). RESULTS: No difference of IIEF-5, IPSS, Qmax, and PVR between two groups in V1. At V3, both groups had improvements of IPSS and group 1 had better improvements (-5.1+/-4.4 vs. -3.1+/-3.9 p<0.001). And Group 1 had larger improvements than Group 2 in Qmax significantly. No difference in PVR in both groups comparing V1 vs. V2 and V1 vs V3. Group 1 had better improved IIEF-5 than Group 2 (V1 vs. V3: 4.8+/-5.8 vs. 4.4+/-5.1; p=0.032). There was no drop out patients due to cardiovascular problems. CONCLUSIONS: Once daily mirodenafil 50mg was more efficacious in treating both ED and LUTS than on-demand dosing mirodenafil 100mg without any complication of cardiovascular problems.

Men With Severe Lower Urinary Tract Symptoms Are at Increased Risk of Depression / 대한배뇨장애요실금학회지

PURPOSE: Lower urinary tract symptoms (LUTS) comprise a set of common, bothersome symptoms in middle-aged and elderly men. Recent research suggests that depressive symptoms may influence the symptoms of benign prostatic hyperplasia (BPH). We performed a community-based cross-sectional study to evaluate the correlation between LUTS and depression. METHODS: The survey was conducted in a rural community during four periods in August 2009, 2010, 2011, and 2012. Two validated questionnaires were used to examine LUTS and depressive symptoms. These included the International Prostate Symptom Score/quality of life (IPSS/QoL) and the Korean version of the Center for Epidemiological Studies-Depression scale (CES-D-K). Patients were categorized in the depressive symptom group if their CES-D-K score was >16 points. RESULTS: A total of 711 men were included in this study. Thirty-five participants (4.92%) were found to have depressive symptoms. There was a positive correlation between depressive symptoms and LUTS severity (P<0.001). As compared to the mild LUTS group, the odds ratio (OR) of depression was 2.868 (95% confidence interval [CI], 1.293-6.362; P for trend<0.001) in the moderate LUTS group, and 4.133 (95% CI, 1.510-11.313; P for trend<0.001) in the severe LUTS group. In a model considering multiple variables such as age, education level, smoking, and exercise, the OR in the moderate LUTS group was 2.534 (1.125-5.708, 95% CI, P for trend=0.005), while that in the severe LUTS group was 3.910 (95% CI, 5.708-11.154; P for trend=0.005). In addition, depression was related to voiding symptoms. CONCLUSIONS: Men with severe LUTS are at higher risk of depression than those with less severe urinary symptoms. The severity of voiding symptoms worsens depression. More aggressive urological diagnosis and treatment is needed in patients with severe LUTS, due to the impact on depressive symptoms and QoL.

Symptom and Differences in Medication Adherence in Method of Administration of Tamsulosin, Finasteride Combination Therapy in Benign Prostatic Hyperplasia

PURPOSE: It has been reported in several for factors on the drug compliance of patients, number of drug being taken, symptom, and pharmaceutical dosage form. However, Studies of drug compliance by dosing methodologies of tamsulosin, finasteride combination therapy and symptom relief for benign prostatic hyperplasia has not been performed. Therefore, we studied for symptom and differences in medication adherence in method of administration of tamsulosin, finasteride combination therapy. MATERIALS AND METHODS: The groups were consisted in need of combination therapy of tamsulosin, finasteride on benign prostatic hyperplasia, one had packaged both drugs together (Group A, n=30) and the other were individually packaged both agents (Group B, n=30). International Prostatic Symptom Score (IPSS) were checked on first, 4weeks, and 8weeks. The evaluation was carried out of medicine compliance by checking the number of drugs 4weeks-interval. which was every 4weeks during 8weeks. RESULTS: The properties other than the PSA in both groups, there was no statistically significant differences between patients. In first 4weeks, drug compliance of each Group A and B had tamsulosin 82.6%, 93.3% (p=0.033), finasteride 80.1%, 93.3% (p=0.042), and last 4weeks tamsulosin 80.6%, 93.7% (p=0.013), finasteride 79.5%, 93.7% (p=0.002) were checked. Group C, D had 81.4%, 96.4% (p=0.021) on 4weeks, 80.6%, 97.2% (p=0.011) on 8weeks. CONCLUSIONS: For co-administration of finasteride and tamsulosin are required in patients with benign prostatic hyperplasia, in order to enhance drug compliance, both tablets have to prescript together in one package to be taken at one time is useful.

The Effect of Terpene Combination on Ureter Calculus Expulsion After Extracorporeal Shock Wave Lithotripsy

PURPOSE: Terpene combination (Rowatinex) is known to help with the expulsion of urinary stones. The aim of this study was to determine how Rowatinex affects the expulsion of remnant stones after shock wave lithotripsy (SWL). MATERIALS AND METHODS: Clinical data were collected retrospectively from 499 patients with a diagnosis of ureteral stones who underwent SWL from January 2009 to August 2012. Ureteral stones were diagnosed in all patients by kidney, ureter, and bladder x-ray and abdominal computed tomography (CT). The progress of patients was documented every 2 weeks to confirm remnant stones after SWL. The patients with remnant stones underwent SWL again. Group 1 consisted of patients who were prescribed an analgesic, Tamsulosin 0.2 mg, and Rowatinex. Group 2 consisted of patients who were prescribed only an analgesic and Tamsulosin 0.2 mg. The expulsion rate of urinary stones was compared between groups. RESULTS: The expulsion rate of urinary stones was not significantly different between the two groups after 2 weeks. However, after 4 weeks, group 1 had a significantly higher expulsion rate (72.2% compared with 61.1%, p=0.022). Fifteen patients (10.2%) in group 1 and 40 (11.4%) in group 2 had to undergo ureteroscopic removal of the stone (p=0.756). Acute pyelonephritis occurred in one patient (0.7%) in group 1 and in one patient (0.3%) in group 2 (p=0.503). CONCLUSIONS: The long-term administration of Rowatinex for 4 weeks increased the expulsion rate of urinary stones after SWL.

A Quality Analysis of Randomized Controlled Trials about Erectile Dysfunction

PURPOSE: A low quality clinical trial could produce errors, and these errors could, in turn, distort the results of the clinical trial. To avoid applying distorted results of trials clinically, a quality analysis of clinical trials is needed. MATERIALS AND METHODS: We selected randomized controlled trials (RCTs) about erectile dysfunction (ED) conducted in Korea using Medline and KoreaMed. Quality assessment of selected RCTs was performed using three assessment tools (Jadad scales, van Tulder scale, Cochrane Collaboration Risk of Bias Tool [CCRBT]). RESULTS: The first RCT about ED conducted in Korea was published in 2002. Since 2002, a total of 20 RCTs have been published in medical journals. Among the 20 articles, only 1 article was found to have a low risk of bias according to the CCRBT. On the Jadad scale, there were 17 high quality articles, while 19 articles were assessed as high quality by the VTS. Only 2 RCTs described the randomization method adequately. Only 1 RCT presented allocation concealment. CONCLUSIONS: A low quality clinical trial could produce errors, and these errors could, in turn, distort the results of the clinical trial. To avoid applying distorted results of trials clinically, a quality analysis of clinical trials is needed. The quality of RCTs was found to be high because almost all of the selected RCTs were double blinded studies. However, the quality of RCTs was inadequate with regard to the lack of randomization and absence of allocation concealment. Therefore, performing adequate randomization and adding a description of the appropriate concealment of allocation may improve the quality of RCTs.