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PURPOSE: Evaluate safety and efficacy of 0.75% phentolamine ophthalmic solution (POS), an alpha-1 antagonist, in reversal of pharmacologically induced mydriasis. DESIGN: Two Phase 3, multicenter, placebo-controlled, randomized, double-masked clinical trials in healthy subjects. SUBJECTS: 553 healthy 12 to 80 year old subjects were randomized 1:1 (MIRA-2) and 2:1 (MIRA-3) to receive either POS or placebo eye drops OU. METHODS: Subjects received POS or placebo administered 1 hour after mydriasis, induced by instillation of either 2.5% phenylephrine, 1% tropicamide, or Paremyd (1% hydroxyamphetamine / 0.25% tropicamide). MAIN OUTCOME MEASURES: Primary endpoint was percent of subjects returning to ≤0.2 mm greater than baseline pupil diameter in study eye at 90 minutes after POS administration. Safety measures included treatment-emergent adverse events (TEAEs) and tolerability measures, including conjunctival hyperemia. RESULTS: In MIRA-2, 185 subjects were randomized to treatment with placebo (94) or POS (91). In MIRA-3, 368 subjects were randomized to treatment with placebo (124) or POS (244). A statistically significant greater percentage of subjects treated with POS had study eyes that showed reversal of mydriasis at 90 minutes (primary endpoint) compared with the placebo treatment (48.9% vs 6.6% for MIRA-2; p<0.0001 and 58% VS 6% for MIRA-3; p<0.0001) and as early as 60 minutes (24.5% vs 5.5% for MIRA-2; p<0.0003 and 42% VS 2% for MIRA-3; p<0.0001). Between 28 to 34% of placebo-treated subjects had not returned to baseline PD at 24 hours following pharmacological dilation compared to 8 to 11% treated with POS (p<0.0001). CONCLUSION: POS treatment had a rapid onset in reducing PD within 60- to 90-minutes, with a statistically significant time savings of 3 to 4 hours to return to baseline PD compared to placebo. One or 2 drops of POS rapidly reversed mydriasis in all subjects regardless of mydriatic agent or iris color. More subjects receiving POS reported a perceived benefit in the resolution of visual symptoms caused by pharmacologically induced mydriasis compared to placebo, with statistically significant differences noted as early as 1 hour. The safety profile was favorable, with the most common adverse effects being mild transient conjunctival hyperemia (11.2%), instillation site discomfort (10.9%), and dysgeusia (3.6%).

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BACKGROUND: Tadalafil, commonly prescribed for benign prostatic hyperplasia (BPH), may benefit patients with Type 2 diabetes mellitus (T2DM) for glycemic markers and complications. However, the association between the long-term use of tadalafil and the incidence of T2DM has not been investigated. METHODS: We emulated a target trial of tadalafil use (5 mg/day) and the risk of T2DM using a population-based claims database in Japan. Patients who initiated tadalafil or alpha-blockers for BPH and had no history of diabetes diagnosis, no dispensing of glucose-lowering drugs, and no history of hemoglobin A1c levels of ≥6.5% (47-48 mmol/mol) were included. The primary outcome was the incidence of T2DM. Pooled logistic regression was used to estimate adjusted risk ratios (RRs) and 5-year cumulative incidence differences (CIDs). RESULTS: A total of 5180 participants initiated tadalafil treatment and were compared with 20,049 patients who initiated alpha-blockers. The median follow-up time for each arm was 27.2 months (interquartile range [IQR], 12.0-47.9) in tadalafil users and 31.3 months (IQR, 13.7-57.2) in alpha-blocker users. The incidence rates of T2DM in tadalafil and alpha-blocker users were 5.4 (95% confidence interval [CI], 4.0-7.2) and 8.8 (95% CI, 7.8-9.8) per 1000-person years, respectively. Initiation of tadalafil was associated with a reduced risk of T2DM (RR, 0.47; 95% CI, 0.39-0.62; 5-year CID, -0.031; 95% CI, -0.040 to -0.019). CONCLUSION: The incidence of T2DM was lower in men with BPH treated with tadalafil than in those treated with alpha-blockers. Thus, tadalafil may be more beneficial than alpha-blockers in preventing T2DM.

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Aneurysmal subarachnoid hemorrhage (aSAH) is characterized by high mortality and morbidity. This scoping review assesses the current evidence regarding the use of sedatives and analgesics in the acute intensive care unit management of aSAH. We conducted a systematic search of Ovid MEDLINE, Ovid Embase, Ovid EmCare, APA PsycInfo, CINAHL, and the Cochrane Database of Systematic Reviews from inception to June 2023. Studies were included if they enrolled intensive care unit patients aged 18 or older with a significant proportion (> 20%) who had aSAH and evaluated the impact of one or more commonly used analgosedatives on physiological parameters in the management of aSAH. The methodological quality of the studies was assessed using the Methodological Index for Nonrandomized Studies score. Of 2,583 articles, 11 met the inclusion criteria. The median sample size was 47 (interquartile range 10-127), and the median Methodological Index for Nonrandomized Studies score was 9.5 (interquartile range 8-11). The studies' publication years ranged from 1980 to 2023. Dexmedetomidine and ketamine showed potential benefits in reducing the incidence of cortical spreading depolarization and delayed cerebral ischemia. Propofol and opioids appeared safe but lacked robust evidence for efficacy. Benzodiazepines were associated with increased delayed cerebral ischemia-related cerebral infarctions and cortical spreading depolarization events. The evidence available to guide the use of analgosedative medications in aSAH is critically inadequate. Dexmedetomidine and ketamine warrant further exploration in large-scale prospective studies because of their potential benefits. Improved study designs with consistent definitions and a focus on patient-centered outcomes are necessary to inform clinical practice.

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BACKGROUND: Urinary dysfunction is an adverse event of low-dose-rate brachytherapy (LDR-BT) in patients with prostate cancer. We aimed to examine the time to α-1 adrenergic antagonist withdrawal after LDR-BT initiation. METHODS: We retrospectively evaluated 1663 patients who underwent LDR-BT at our hospital during 2004-2022. RESULTS: Overall, 1485/1663 (89.3%) patients were able to stop using α-1 adrenergic antagonists, 1111 (66.8%) of them within 1 year of LDR-BT. Risk factors for prolonged time to withdrawal were age ≥70 years, taking agents for lower urinary tract symptoms prior to LDR-BT, an International Prostate Symptom Score ≥8, an Overactive Bladder Symptom Score ≥3 and a residual urine volume ≥20 ml. Of the patients who were able to stop taking α-1 adrenergic antagonists, 357/1485 (24.0%) required resumption, 218 (61.1%) of whom did so between 1 and 3 years after LDR-BT. This period matched the period of transient worsening of the urinary symptom score. Finally, multivariable analysis identified supplemental external beam radiotherapy and an Overactive Bladder Symptom Score ≥3 as independent risk factors for α-1 adrenergic antagonist resumption. CONCLUSIONS: Withdrawal of α-1 adrenergic antagonists was possible in 66.8% of patients within 1 year of LDR-BT. Our results suggest that patients who are older or have pre-treatment LUTS may have prolonged deterioration of urinary dysfunction after treatment. Resumption of α-1 adrenergic antagonists 1-3 years after treatment may be associated with urinary symptom flares, and close attention is necessary for patients with supplemental external beam radiotherapy and a high pretreatment Overactive Bladder Symptom Score.

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OBJECTIVE: To determine a conversion factor for use when switching from dexmedetomidine infusion to enteral clonidine in critically ill neonates. METHODS: This was an observational, retrospective review of conversions from dexmedetomidine to -clonidine, performed in a neonatal intensive care unit (NICU) between January 2020 and December 2021. Both initial conversion factors and those resulting after a 48-hour titration period were examined. Sedation and withdrawal scores were measured, and doses were titrated based on a standardized practice within the unit. RESULTS: A total of 43 dexmedetomidine to clonidine conversions were included. The median (IQR) dexmedetomidine dose prior to conversion was 17.4 (11.3-24.0) mcg/kg/day (0.7 mcg/kg/hr) and the median (IQR) enteral clonidine dose post titration was 7.8 (4.7-9.3) mcg/kg/day (2 mcg/kg every 6 hours). This equated to a post-titration conversion factor of approximately 0.42. All neonates had also received opioid infusions while on dexmedetomidine and 60% were on concurrent opioids at the time of the clonidine conversion. CONCLUSIONS: Neonatal clinicians may find the conversion factor identified in this study a useful starting point when converting from dexmedetomidine infusion to enteral clonidine in practice and should be -reminded of the most important steps in conversions (monitoring and follow-up) owing to the variability in this patient group. More studies are needed to elucidate the impact of patient-specific factors on this -conversion process.

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PURPOSE: This study investigated the effect of administering tamsulosin before surgery on the successful insertion of a 12/14 French (F) ureteral access sheath (UAS) during the procedure, as well as the impact of preoperative and postoperative tamsulosin use on symptoms related to the ureteral stent. MATERIALS AND METHODS: This study was a randomized, single-center, double-blinded, placebo-controlled trial involving 200 patients who underwent unilateral retrograde intrarenal surgery. Patients received either tamsulosin (0.4 mg) or placebo 1 week before surgery until stent removal. Patients were randomly assigned to one of four groups. Group 1 received tamsulosin throughout the study period. Group 2 received tamsulosin before surgery and placebo after surgery. Group 3 received placebo before surgery and tamsulosin after surgery. Group 4 received placebo before and after surgery. The USSQ (Ureteral Stent Symptom Questionnaire) was completed between postoperative days 7 and 14 immediately before stent removal. RESULTS: A total of 160 patients were included in this analysis. Their mean age was 55.0±11.0 years, and 48 patients (30.0%) were female. In the group that received preoperative tamsulosin, the success rate of 12/14F UAS deployment was significantly higher than that of the preoperative placebo group (88.0 vs. 75.3%, p=0.038). Preoperative and postoperative tamsulosin did not significantly alleviate symptoms related to the ureteral stent. CONCLUSIONS: Our results revealed that preoperative administration of tamsulosin improved the success of larger-sized UAS, whereas preoperative and postoperative tamsulosin use did not significantly alleviate symptoms related to ureteral stents.

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BACKGROUND: Dexmedetomidine, a highly selective alpha-2 adrenoceptor agonist with sedative and analgesic effects, has been suggested in recent studies to possess renoprotective properties. Dexmedetomidine may reduce the incidence of delayed graft function and contribute to effective pain control post-renal transplantation. The primary objective of this systematic review was to assess whether dexmedetomidine decreases the occurrence of delayed graft function in renal transplant patients. METHODS: Databases including MEDLINE, EMBASE, and CENTRAL were comprehensively searched from their inception until March 2023. The inclusion criteria covered all Randomized Clinical Trials (RCTs) and observational studies comparing dexmedetomidine to control in adult patients undergoing renal transplant surgery. Exclusions comprised case series and case reports. RESULTS: Ten RCTs involving a total of 1358 patients met the eligibility criteria for data synthesis. Compared to the control group, the dexmedetomidine group demonstrated a significantly lower incidence of delayed graft function (OR = 0.71, 95% CI 0.52-0.97, p = 0.03, GRADE: Very low, I2 = 0%). Dexmedetomidine also significantly prolonged time to initiation of rescue analgesia (MD = 6.73, 95% CI 2.32-11.14, p = 0.003, GRADE: Very low, I2 = 93%) and reduced overall morphine consumption after renal transplant (MD = -5.43, 95% CI -7.95 to -2.91, p < 0.0001, GRADE: Very low, I2 = 0%). The dexmedetomidine group exhibited a significant decrease in heart rate (MD = -8.15, 95% CI -11.45 to -4.86, p < 0.00001, GRADE: Very low, I2 = 84%) and mean arterial pressure compared to the control group (MD = -6.66, 95% CI -11.27 to -2.04, p = 0.005, GRADE: Very low, I2 = 87%). CONCLUSIONS: This meta-analysis suggests that dexmedetomidine may potentially reduce the incidence of delayed graft function and offers a superior analgesia profile as compared to control in adults undergoing renal transplants. However, the high degree of heterogeneity and inadequate sample size underscore the need for future adequately powered trials to confirm these findings.

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Background: Impaired glucose and energy metabolism has been suggested as a pathogenic mechanism underlying Parkinson's disease (PD). In recent cohorts, phosphoglycerate kinase 1 activators (PGK1a) have been associated with a lower incidence of PD when compared with other antiprostatic agents that do not activate PGK1. Objective: We aimed to perform a systematic review and meta-analysis comparing the incidence of PD in patients taking PGK1a versus tamsulosin. Methods: We searched PubMed, Embase, and Cochrane Library for studies comparing PGK1a vs. tamsulosin in adults and elderly. The primary outcome was the incidence of PD. We computed hazard ratios (HR) for binary endpoints, with 95% confidence intervals (CIs). Statistical analysis was performed using Review Manager 5.4 and R (version 4.3.1). Results: A total of 678,433 participants from four cohort studies were included, of whom 287,080 (42.3%) received PGK1a. Mean age ranged from 62 to 74.7 years and nearly all patients were male. Patients taking PGK1a had a lower incidence of PD (PGK1a 1.04% vs. tamsulosin 1.31%; HR 0.80; 95% CI 0.71-0.90; p < 0.01). This result remained consistent in a sensitivity analysis excluding patients of age 60 years old or younger (PGK1a 1.21% vs. tamsulosin 1.42%; HR 0.82; 95% CI 0.71-0.95; p < 0.01). Conclusions: Glycolysis-enhancing drugs are associated with a lower incidence of PD when compared with tamsulosin in adults and elderly individuals with prostatic disease in use of alpha-blockers. Our findings support the notion of glycolysis as a potential neuroprotective mechanism in PD. Future investigations with randomized controlled trials are needed.

It has been suggested that impairment in glucose and energy metabolism is one of the mechanisms underlying the development of Parkinson's disease. In recent studies, medications traditionally prescribed for prostate diseases, called phosphoglycerate kinase 1 activators (PGK1a), have been associated with a lower incidence of Parkinson's disease when compared to other medications for the same purpose that do not activate the same energetic pathway. Therefore, we thoroughly reviewed the literature and combined the results of studies that compared both medications (PGK1a versus another medication  that  does not activate this energetic pathway, called tamsulosin), evaluating the incidence of Parkinson's disease in both groups. We included a total of 678,433 individuals, of whom 42.3% received PGK1a and 57.7% received tamsulosin. In our analysis, patients taking PGK1a had a lower incidence of Parkinson's disease when compared to the other group, even when we excluded patients younger than 60 years of age. As a result, our findings support the notion that the increase of energy metabolism is a potential neuroprotective mechanism in Parkinson's disease and future investigations are needed.

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INTRODUCTION: The objectives of the study were to examine the opinions of urology specialists on whether there are actual differences in efficacy among α1-blockers and to identify the factors that should be considered when prescribing these medications according to age. METHODS: We surveyed 50 South Korean urology specialists with over 3 years of clinical experience in secondary or tertiary hospitals in July-August 2021. The survey covered urologists' demographics, awareness of α1-blocker prescription differences, and key factors in α1-blocker selection based on LUTS severity and patient age. RESULTS: Overall, 82% of the respondents believed that there were differences in the efficacy of α1-blockers in actual practice according to age. Over 90% of the respondents agreed on the need for head-to-head comparison studies to compare the effects of different α1-blockers. Regardless of the severity of LUTS, urologists prioritize cardiovascular side effects when prescribing α1-blockers to patients aged ≥70 years. Further, 19% of the urologists prioritized ejaculatory side effects for mild-to-moderate LUTS and 9% for severe LUTS (p < 0.001). CONCLUSIONS: This study shows that head-to-head studies comparing the efficacy of different α1-blockers are highly valuable for the real-world clinical application of α1-blockers. Notably, urologists prioritize cardiovascular and ejaculatory side effects in older and younger patients while prescribing α1-blockers, respectively.

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Clinical studies have shown that α1-adrenergic receptor antagonists (α-blockers) are associated with increased heart failure risk. The mechanism underlying that hazard and whether it arises from direct inhibition of cardiomyocyte α1-ARs or from systemic effects remain unclear. To address these issues, we created a mouse with cardiomyocyte-specific deletion of the α1A-AR subtype and found that it experienced 70% mortality within 7 days of myocardial infarction driven, in part, by excessive activation of necroptosis. We also found that patients taking α-blockers at our center were at increased risk of death after myocardial infarction, providing clinical correlation for our translational animal models.

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BACKGROUND: Although brimonidine is currently used in the clinical treatment of glaucoma and rosacea, research of the deep sedative effect on animals after systemic administration is reported firstly and has shown promising results. METHODS: The median effective dose (ED50 ), the median lethal dose (LD50 ), and the therapeutic index of brimonidine for deep sedation and formalin stimulation assay were determined by various animal experiments. The effect of synergistic anesthesia in rabbits with brimonidine and chloral hydrate was preliminarily evaluated. RESULTS: The ED50 of brimonidine for highly effective sedation by intraperitoneal injection in rats was calculated to be 2.05 mg kg-1 with a 95% confidence interval (CI) of 1.87 to 2.25 mg kg-1 . The ED50 of brimonidine for deep sedation by intravenous and intrarectal injection in rabbits was calculated to be 0.087 mg kg-1 with a 95% CI of 0.084 to 0.091 mg kg-1 and 1.65 mg kg-1 with a 95% CI of 1.43 to 1.91 mg kg-1 , respectively. The LD50 of intraperitoneal brimonidine injection in rats was calculated to be 468 mg kg-1 with a 95% CI of 441 to 497 mg kg-1 and a therapeutic index of 228. Brimonidine has a certain analgesic and heart rate lowering effects. CONCLUSION: The results confirmed that brimonidine has deep sedation and analgesic effects after systemic administration and has high safety. It can be used in combination with other types of sedative drugs to achieve better effects.

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BACKGROUND: It is uncertain how long combination therapy should be continued in patients with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). We investigated the withdrawal effects of α1-adrenergic receptor blocker (AB) or 5α-reductase inhibitor (5ARI) following successful combination therapy. METHODS: This prospective, randomized, open-label, parallel trial enrolled 222 patients with BPH/LUTS who showed at least a seven-point improvement in International Prostate Symptom Score-total (IPSS-T) and a ≥ 20% reduction in prostate volume (PV) following the initiation of combination therapy. Patients were randomized in a 1:1:1 ratio into continued-combination, AB-withdrawal, and 5ARI-withdrawal groups. IPSS, overactive bladder symptom score, EuroQol-five-dimensional questionnaire (EQ-5D-5L), EuroQol-visual analog scale (EQ-VAS), prostate volume (PV), maximal flow rate, postvoid residual urine (PVR), and prostate-specific antigen level were assessed every 6 months for 24 months. The predictors of IPSS-T deterioration were evaluated. RESULTS: At Month 24, IPSS-T deterioration (≥2 point) was observed in 20/72 (27.8%) and 19/72 (26.4%) patients in the AB- and 5ARI-withdrawal groups, respectively. Among them, 4/72 (5.6%) and 4/70 (5.7%) patients required readdition of the withdrawn drug (p = 0.868). In the continued combination group, EQ-VAS improved at Month 24 compared to baseline (p = 0.028). At Month 24, the AB-withdrawal group showed improvements in EQ-5D-5L, EQ-VAS, and PVR (all p < 0.005), while the 5ARI-withdrawal group showed improvement in IPSS-S (p = 0.011). Diabetes mellitus was associated with IPSS-T deterioration at Month 24 (p = 0.020). CONCLUSIONS: In patients with BPH/LUTS who are reluctant to continue combination therapy, AB or 5ARI withdrawal may be offered in men with improvement in IPSS-T by at least seven points and reduction in PV by at least 20%.

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ABSTRACT Purpose: Medical expulsive therapy (MET) is recommended for distal ureteral stones from 5 to 10 mm. The best drug for MET is still uncertain. In this review, we aim to compare the effectiveness of tadalafil and tamsulosin for distal ureteral stones from 5 to 10 mm in terms of stone expulsion rate (SER), stone expulsion time (SET) and the side effect profile. Materials and methods: A comprehensive literature search was conducted on MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Scopus and Web of Science, from inception until April 2023. Only randomized controlled trials were included in the analysis. Results: Eleven publications with 1,330 patients were included. We observed that tadalafil has a higher SER (OR 0.55, CI 95% 0.38;0.80, p=0.02, I2=52%) and the same efficacy in SET (MD 1.07, CI 95% -0.25; 2.39, p=0.11, I2=84%). No differences were found when comparing side effects as headache, backache, dizziness, and orthostatic hypotension. Conclusion: Tadalafil has a higher stone expulsion rate than tamsulosin as a medical expulsive therapy for patients with distal stones from 5 to 10 mm without differences in side effects.

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Depressive disorders (DD) are common, and their prevalence is expected to rise over the next decade. Depressive disorders are linked to significant morbidity and mortality. The clinical conundrum of depressive disorders lies in the heterogeneity of their phenomenology and etiology. Further, the currently available antidepressants have several limitations, including a delayed onset of action, limited efficacy, and an unfavorable side effect profile. In this review, Dexmedetomidine (DEX), a highly selective and potent α2-adrenergic receptor (α2-AR) agonist, is proposed as a potentially novel antidepressant with multiple mechanisms of action targeting various depression pathophysiological processes. These mechanisms include modulation of the noradrenergic system, regulation of neuroinflammation and oxidative stress, influence on the Brain-Derived Neurotrophic Factor (BDNF) levels, and modulation of neurotransmitter systems, such as glutamate. The review begins with an introduction before moving on to a discussion of DEX's pharmacological features. The pathophysiological and phenomenological targets of DD are also explored, along with the review of the existing preclinical and clinical evidence for DEX's putative anti-depressant effects. Finally, the review ends by presenting the pertinent conclusions and future directions.

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PURPOSE: Medical expulsive therapy (MET) is recommended for distal ureteral stones from 5 to 10 mm. The best drug for MET is still uncertain. In this review, we aim to compare the effectiveness of tadalafil and tamsulosin for distal ureteral stones from 5 to 10 mm in terms of stone expulsion rate (SER), stone expulsion time (SET) and the side effect profile. MATERIALS AND METHODS: A comprehensive literature search was conducted on MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Scopus and Web of Science, from inception until April 2023. Only randomized controlled trials were included in the analysis. RESULTS: Eleven publications with 1,330 patients were included. We observed that tadalafil has a higher SER (OR 0.55, CI 95% 0.38;0.80, p=0.02, I2=52%) and the same efficacy in SET (MD 1.07, CI 95% -0.25; 2.39, p=0.11, I2=84%). No differences were found when comparing side effects as headache, backache, dizziness, and orthostatic hypotension. CONCLUSION: Tadalafil has a higher stone expulsion rate than tamsulosin as a medical expulsive therapy for patients with distal stones from 5 to 10 mm without differences in side effects.

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BACKGROUND: An association between adrenergic alpha-1 receptor antagonists and delirium has been suggested, but the details are unclear. AIM: This study investigated the association between adrenergic alpha-1 receptor antagonists and delirium in patients with benign prostatic hyperplasia using the Japanese Adverse Drug Event Report database. METHOD: First, disproportionality analysis compared the frequency of delirium in the adrenergic alpha-1 receptor antagonists silodosin, tamsulosin, and naftopidil. Next, multivariate logistic analysis was performed to examine the association between delirium and adrenergic alpha-1 receptor antagonists where disproportionality was detected. RESULTS: A disproportionality in delirium was observed in patients receiving tamsulosin (reporting odds ratio [ROR] 1.85, 95% confidence interval [CI] 1.38-2.44, P < 0.01) compared with those who did not, and also in patients receiving naftopidil (ROR 2.23, 95% CI 1.45-3.28, P < 0.01) compared with those who did not. Multivariate logistic analysis revealed that in addition to previously reported risk factors for delirium, delirium in patients receiving tamsulosin was significantly increased with concomitant use of anticholinergics (odds ratio 2.73, 95% CI 1.41-5.29, P < 0.01) and delirium in patients receiving naftopidil was significantly increased with concomitant use of beta3-adrenergic receptor agonists (odds ratio 4.19, 95% CI 1.66-10.6, P < 0.01). CONCLUSION: Anticholinergics or beta3-adrenergic receptor agonists to treat overactive bladder in patients receiving tamsulosin and naftopidil was strongly associated with delirium. Confirming the medical history and concomitant medications of patients receiving tamsulosin or naftopidil may contribute to preventing delirium in patients with benign prostatic hyperplasia and to improving their outcomes.

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Background: The pharmacological treatment of urinary incontinence (UI) may involve bladder antimuscarinics, which can generate risks in the elderly. Objective: The aim was to determine the treatment patterns of a group of patients with UI and possible potentially inappropriate prescriptions. Design and methods: This was a cross-sectional study that identified prescription patterns of medications for outpatient use in patients with UI between December 2020 and November 2021 based on a population database of members of the Colombian Health System. Patients were identified based on the codes of the international classification of diseases, version-10. Sociodemographic and pharmacological variables were considered. Results: A total of 9855 patients with UI were identified, with a median age of 72 years, and 74.6% were women. Unspecified UI was the most frequent form (83.2%), followed by specified UI (7.9%), stress UI (6.7%), and UI associated with an overactive bladder (2.2%). A total of 37.2% received pharmacological treatment, mainly with bladder antimuscarinics (22.6%), mirabegron (15.6%), and topical estrogens (7.9%). Pharmacological management predominated in UI associated with overactive bladder, in women and in patients between 50 and 79 years of age. Of the patients who received bladder antimuscarinics, 54.5% were 65 years old or older, and 21.5% also had benign prostatic hyperplasia, sicca syndrome, glaucoma, constipation, or dementia. A total of 2.0% of women had been prescribed systemic estrogens and 1.7% had been prescribed peripheral α-adrenergic antagonists. Conclusion: Differences in the prescriptions were found according to the type of UI, sex, and age group. Potentially inappropriate or risky prescriptions were common.

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This meta-analysis investigated the efficacy and adverse drug reactions (ADRs) of three different adrenergic alpha-antagonists during the treatment of pediatric ureteral stones. Studies were retrieved from MEDLINE, EMBASE, and the Cochrane Controlled Trial Registry until January 2022. We identified 7 articles, including six RCTs and one cohort study. 610 children received either adrenergic alpha-antagonists or placebo. The results confirmed that the three different adrenergic alpha-antagonists could significantly increase the ureteral calculi expulsive rate and shorten the ureteral calculi expulsive time, regardless of the size of the stone "<5 mm" or "5-10 mm". Subgroup analysis suggested that all three adrenergic alpha-antagonists increased the ureteral calculi expulsive rate. Tamsulosin and silodosin also have the effect of shortening ureteral calculi expulsive time, while doxazosin has an insignificant effect on ureteral calculi expulsive time. Besides, tamsulosin and silodosin obviously reduced the number of pain episodes caused by ureteral calculi in children. We analyzed the treatment-emergent adverse events (TEAEs) caused by the treatment of three different adrenergic alpha-antagonists to explore their ADRs. The probability of ADRs was increased after treatment with adrenergic alpha-antagonists. Further subgroup analysis revealed the application of tamsulosin was positively correlated with ADRs in children with ureteral calculi, while the application of doxazosin and silodosin had no statistically significant effect on the probability of TEAEs. In a conclusion, this article systematically analyzed the efficacy and ADRs of three different adrenergic alpha-antagonists, and provided reference and guidance for the application of adrenergic alpha-antagonists to treat children ureteral calculi.