RESUMO
PURPOSE: The study aimed to determine the typical clearance and volume of distribution values of tamsulosin in patients with benign prostatic hyperplasia (BPH), and to identify factors with a measurable impact on the drug's elimination. METHODS: This open-label, single-arm population pharmacokinetic study involved 65 adult men with BPH who had been on tamsulosin therapy for at least seven days. The steady-state serum concentrations of tamsulosin were measured using liquid chromatography-tandem quadrupole mass spectrometry. Population pharmacokinetic parameters, their variability, and influencing factors were estimated based on a two-compartment pharmacokinetic model using NONMEM software. RESULTS: The estimated tamsulosin clearance in BPH patients was 0.719 L/h, and the steady-state volume of distribution was 32 L. Neither renal nor liver function parameters had a statistically significant effect on tamsulosin clearance. However, a positive correlation was observed between hemoglobin levels and tamsulosin clearance in the BPH patient cohort. CONCLUSION: Our investigation reveals significant associations between tamsulosin pharmacokinetics and specific characteristics of patients with lower urinary tract symptoms (LUTS) due to BPH. The study highlights that tamsulosin clearance is associated with hemoglobin levels in patients with LUTS/BPH. This study underscores the importance of considering patient-specific factors when managing BPH treatment with tamsulosin, emphasizing associations rather than causative relationships.
Assuntos
Hiperplasia Prostática , Tansulosina , Humanos , Hiperplasia Prostática/tratamento farmacológico , Masculino , Tansulosina/farmacocinética , Tansulosina/uso terapêutico , Idoso , Pessoa de Meia-Idade , Antagonistas de Receptores Adrenérgicos alfa 1/farmacocinética , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Idoso de 80 Anos ou mais , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Sintomas do Trato Urinário Inferior/etiologiaAssuntos
Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Serenoa , Humanos , Hiperplasia Prostática/complicações , Hiperplasia Prostática/tratamento farmacológico , Masculino , Sintomas do Trato Urinário Inferior/etiologia , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Fitoterapia/métodos , Resultado do Tratamento , Pessoa de Meia-Idade , IdosoRESUMO
PURPOSE: To evaluate efficacy and safety of beta-3 adrenergic agonists in adults with neurogenic lower urinary tract dysfunction. MATERIALS AND METHODS: According to a protocol (CRD42022350079), we searched multiple data sources for published and unpublished randomized controlled trials (RCTs) up to 2nd August 2022. Two review authors independently screened studies and abstracted data from the included studies. We performed statistical analyses by using a random-effects model and interpreted them according to the Cochrane Handbook for Systematic Reviews of Interventions. We used GRADE guidance to rate the certainty of evidence (CoE). RESULTS: We found data to inform two comparisons: beta-3 adrenergic agonists versus placebo (4 RCTs) and anticholinergics (2 RCTs). Only mirabegron was used for intervention in all included studies. Compared to placebo, beta-3 adrenergic agonists may have a clinically unimportant effect on urinary symptoms score (mean difference [MD] -2.50, 95% confidence interval [CI] -4.78 to -0.22; I²=92%; 2 RCTs; 192 participants; low CoE) based on minimal clinically important difference of 3. We are very uncertain of the effects of beta-3 adrenergic agonists on quality of life (MD 10.86, 95% CI 1.21 to 20.50; I²=41%; 2 RCTs; 98 participants; very low CoE). Beta-3 adrenergic agonists may result in little to no difference in major adverse events (cardiovascular adverse events) (risk ratio 0.57, 95% CI 0.14 to 2.37; I²=0%; 4 RCTs; 310 participants; low CoE). Compared to anticholinergics, no study reported urinary symptom scores and quality of life. There were no major adverse events (cardiovascular adverse events) in either study group (1 study; 60 participants; very low CoE). CONCLUSIONS: Compared to placebo, beta-3 adrenergic agonists may have similar effects on urinary symptom scores and major adverse events. There were uncertainties about their effects on quality of life. Compared to anticholinergics, we are either very uncertain or have no evidence about urinary symptom scores, quality of life, and major adverse events.
Assuntos
Agonistas de Receptores Adrenérgicos beta 3 , Bexiga Urinaria Neurogênica , Humanos , Agonistas de Receptores Adrenérgicos beta 3/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 3/efeitos adversos , Bexiga Urinaria Neurogênica/tratamento farmacológico , Resultado do Tratamento , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
During the last two decades botulinum toxin has also conquered urology. Botulinum toxin reduces the contractility and sensitivity of the detrusor muscle and relieves pain. It is therefore a promising drug whose use in men also appears promising. The following article highlights the practical relevance of botulinum toxin for male lower urinary tract symptoms (LUTS). But first of all, a distinction must be made between use in male LUTS due to benign prostate syndrome (BPS) and use in cases of overactive bladder (OAB) alone. A differentiated diagnosis and treatment of male LUTS is therefore essential.
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Sintomas do Trato Urinário Inferior , Bexiga Urinária Hiperativa , Humanos , Masculino , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Bexiga Urinária Hiperativa/tratamento farmacológico , Toxinas Botulínicas/uso terapêutico , Toxinas Botulínicas Tipo A/uso terapêutico , Toxinas Botulínicas Tipo A/administração & dosagem , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/complicações , Fármacos Neuromusculares/uso terapêutico , Fármacos Neuromusculares/farmacologiaRESUMO
Objectives: To examine time-dependent functional and structural changes of the lower urinary tract in streptozotocin-induced diabetic rats with or without low-dose insulin treatment and explore the pathophysiological characteristics of insulin therapy on lower urinary tract dysfunction (LUTD) caused by diabetes mellitus (DM). Methods: Female Sprague-Dawley rats were divided into five groups: normal control (NC) group, 4 weeks insulin-treated DM (4-DI) group, 4 weeks DM (4-DM) group, 8 weeks insulin-treated DM (8-DI) group and 8 weeks DM (8-DM) group. DM was initially induced by i.p. injection of streptozotocin (65 mg/kg), and then the DI groups received subcutaneous implantation of insulin pellets under the mid dorsal skin. Voiding behavior was evaluated in metabolic cages. The function of bladder and urethra in vivo were evaluated by simultaneous recordings of the cystometrogram and urethral perfusion pressure (UPP) under urethane anesthesia. The function of bladder and urethra in vitro were tested by organ bath techniques. The morphologic changes of the bladder and urethra were investigated using Hematoxylin-Eosin and Masson's staining. Results: Both 4-and 8-weeks diabetic rats have altered micturition patterns, including increased 12-h urine volume, urinary frequency/12 hours and voided volume. In-vivo urodynamics showed the EUS bursting activity duration is longer in 4-DM group and shorter in 8-DM group compared to NC group. UPP change in 8-DM were significantly lower than NC group. While none of these changes were found between DI and NC groups. Organ bath showed the response to Carbachol and EFS in bladder smooth muscle per tissue weights was decreased significantly in 4- and 8-weeks DM groups compared with insulin-treated DM or NC groups. In contrast, the contraction of urethral muscle and maximum urethral muscle contraction per gram of the tissue to EFS stimulation were significantly increased in 4- and 8-weeks DM groups. The thickness of bladder smooth muscle was time-dependently increased, but the thickness of the urethral muscle had no difference. Conclusions: DM-induced LUTD is characterized by time-dependent functional and structural remodeling in the bladder and urethra, which shows the hypertrophy of the bladder smooth muscle, reduced urethral smooth muscle relaxation and EUS dysfunction. Low-dose insulin can protect against diuresis-induced bladder over-distention, preserve urethral relaxation and protect EUS bursting activity, which would be helpful to study the slow-onset, time-dependent progress of DM-induced LUTD.
Assuntos
Diabetes Mellitus Experimental , Insulina , Ratos Sprague-Dawley , Uretra , Bexiga Urinária , Micção , Animais , Feminino , Ratos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/induzido quimicamente , Insulina/administração & dosagem , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Sintomas do Trato Urinário Inferior/etiologia , Sintomas do Trato Urinário Inferior/fisiopatologia , Estreptozocina/toxicidade , Fatores de Tempo , Uretra/efeitos dos fármacos , Uretra/fisiopatologia , Uretra/patologia , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/fisiopatologia , Bexiga Urinária/patologia , Micção/efeitos dos fármacosRESUMO
INTRODUCTION: Alpha-adrenergic antagonists are widely prescribed for lower urinary tract symptoms (LUTS), however there has been a report that their use is associated with dementia. Our objective was to investigate if new users of alpha-adrenergic antagonists with varying levels of cognitive impairment had an increased risk of cognitive decline compared to non-users. METHODS: This was a retrospective cohort study, utilizing data from the National Alzheimer's Coordinating Center (NACC) data set. After applying relevant exclusion criteria, 916 people who were newly using alpha-antagonist medications were matched with a propensity score to 916 who were not using these medications. The primary outcome was a clinically relevant cognitive decline measured by the Clinical Dementia Rating (CDR) Dementia Staging Instrument or the mini mental state examination (MMSE). Secondary outcomes included scores from other cognitive assessment tools. RESULTS: The matched cohorts did not differ significantly in baseline characteristics. There were no statistically significant differences in baseline or follow-up cognitive scores between those exposed and nonexposed to alpha-adrenergic antagonists. Clinically significant cognitive decline (as defined by the CDR) occurred in 9.72% of the exposed group and 8.19% of the nonexposed group. There was no observed effect of alpha-adrenergic antagonists on cognitive decline, as measured with the CDR (odds ratio [OR] 1.34, p = 0.14) or the MMSE (OR 0.98, p = 0.92). Stratified analyses by cognitive status and apolipoprotein E genotype interaction assessment also demonstrated no significant associations. CONCLUSION: Alpha-adrenergic antagonists for LUTS do not appear to increase the risk of cognitive decline, offering reassurance to clinicians and patients.
Assuntos
Antagonistas Adrenérgicos alfa , Cognição , Disfunção Cognitiva , Sintomas do Trato Urinário Inferior , Humanos , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Sintomas do Trato Urinário Inferior/fisiopatologia , Sintomas do Trato Urinário Inferior/diagnóstico , Masculino , Feminino , Idoso , Estudos Retrospectivos , Antagonistas Adrenérgicos alfa/efeitos adversos , Antagonistas Adrenérgicos alfa/farmacologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Cognição/efeitos dos fármacos , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Polypharmacy exacerbates lower urinary tract symptoms (LUTS). Japan exhibits a higher prevalence of concomitant medication use in drug therapy than other countries. Previous age- and sex-specific reports exist; however, none include patients of all ages. Therefore, this retrospective study determined the impact of polypharmacy and its associated risk factors on LUTS exacerbation in outpatients with urological conditions. We included patients receiving medication who visited the Department of Urology at the Gifu Municipal Hospital (Gifu, Japan) between January, 2018 and December, 2018. The association between LUTS and polypharmacy and the risk factors for LUTS exacerbation were investigated. Patients were categorized into two groups according to their polypharmacy status. We performed propensity score matching and compared the International Prostate Symptom Score (IPSS) between the groups using the unpaired t-test. Multiple logistic regression analysis was performed to examine the risk factors, including "polypharmacy" and "taking multiple anticholinergic medications" for LUTS exacerbation. When comparing the IPSS between the groups, the polypharmacy group was found to have significantly higher scores than the non-polypharmacy group in six items, including "total score" and "storage score." Multiple logistic regression analysis results showed high significance in three items, including "polypharmacy" (odds ratio (OR) = 1.67, 95% confidence interval (CI): 1.03-2.71) and "taking multiple anticholinergic medications" (OR = 8.68, 95% CI: 1.05-71.7). In conclusion, this study revealed that "polypharmacy" and "taking multiple anticholinergic medications" were risk factors for LUTS. Particularly, "polypharmacy" is associated with storage symptom exacerbation. Therefore, eliminating "polypharmacy" and "taking multiple anticholinergic medications" is expected to improve LUTS.
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Sintomas do Trato Urinário Inferior , Polimedicação , Masculino , Feminino , Humanos , Estudos Retrospectivos , Japão/epidemiologia , Hospitais Municipais , Fatores de Risco , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Sintomas do Trato Urinário Inferior/epidemiologia , Sintomas do Trato Urinário Inferior/diagnóstico , Antagonistas Colinérgicos/efeitos adversosRESUMO
AIM: The aim of the observational cohort study is to study and evaluate the efficiency of the drug Adenoprosin in combination with other drugs in comparison with monotherapy. MATERIALS AND METHODS: Data from 6,442 patients at 221 medical institutions in 39 cities from November 2020 to December 2022 were analyzed. The drug Adenoprosin in the form of rectal suppositories was prescribed as monotherapy in group I, while patients in group II received Adenoprosin in a combination with other drugs. The efficacy of treatment was assessed using uroflowmetry data, prostate volume, postvoid residual volume and validated scales (NIH-CPSI, IIEF-5, IPSS, QoL). RESULTS: The diagnosis was validated in 6375 cases, including BPH (n=1498), chronic prostatitis (CP; n=3060), and in combination of both disorders (n=1817). A total of 3580 patients received Adenoprosin as monotherapy, while 2761 received combination therapy. In most cases, a combination therapy was prescribed in case of more severe disease. In patients with BPH, positive changes after treatment were noted in favor of group I according to change in postvoid residual volume (p<0.001) and prostate volume (p<0.001). Combination therapy demonstrated significant positive changes compared with monotherapy when assessing NIH-CPSI scores (p=0.005), IPSS scores (p<0.001) and the mean maximum urine flow rate (Qmax; p<0.001). Qmax increased significantly in both groups (from 14 ml/s to 17 ml/s in group I and from 12 ml/s to 14 ml/s in group II). CONCLUSION: Treatment of BPH, CP and their combination is a complex clinical task. The multiple nature of complaints often dictates the need for simultaneous administration of two or more drugs. Combination therapy involves the use of multiple therapeutic strategies to treat different aspects of BPH and CP. In patients with BPH, a combination therapy has been shown to be more effective than monotherapy with either class of drugs, as it reduces the risk of disease progression, acute urinary retention, and the need for surgery. However, combination therapy should be considered on an individual basis, taking into account symptoms, prostate size and overall health. There is no universal treatment method for BPH suitable for any patient. The treatment strategy should be chosen individually, considering all medical and social factors. All of the above applies to a large extent to the treatment of CP and CP + BPH. According to our results, Adenoprosin demonstrated efficacy both as monotherapy and in combination with other traditional drugs in the treatment of men with lower urinary tract symptoms.
Assuntos
Quimioterapia Combinada , Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Humanos , Masculino , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/complicações , Pessoa de Meia-Idade , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Sintomas do Trato Urinário Inferior/fisiopatologia , Idoso , Prostatite/tratamento farmacológico , Estudos de Coortes , Resultado do TratamentoRESUMO
INTRODUCTION AND HYPOTHESIS: Phosphodiesterase enzymes are widely distributed in female urogenital tissues. Yet, the understanding of their physiological roles and the impact of phosphodiesterase inhibitors on lower urinary tract symptoms in women remains limited. Current hypotheses are conflicting: one suggests that vasodilation might expand the periurethral vascular plexus, leading to increased urethral pressure, whereas the other proposes a relaxation of urethral musculature, resulting in decreased pressure. To further clarify this, we investigated the effect of tadalafil on the opening urethral pressure and voiding function in healthy women. METHODS: We conducted a randomized, double-blind, placebo-controlled crossover trial involving 24 healthy women. Participants were randomly assigned to receive a single dose of tadalafil (40 mg) or placebo during their initial visit and then switched to the alternative treatment during their second visit. Opening urethral pressure was measured with urethral pressure reflectometry during both resting and squeezing conditions of the pelvic floor. Subsequently, voiding parameters were recorded. RESULTS: Compared with placebo, a single dose of tadalafil significantly reduced opening urethral pressure during both resting (-6.8 cmH20; 95% confidence interval [CI], -11.8 to -1.9; p = 0.009) and squeezing conditions (-8.8 cmH20; 95% CI, -14.6 to -3.1; p = 0.005). Voiding parameters did not show significant differences (average flow rate: -0.8 ml/s [95% CI, -2.0 to 0.4; p = 0.2]; maximum flow rate: -1.7 ml/s [95% CI, -4.8 to 1.5; p = 0.3]). CONCLUSIONS: A single dose of 40 mg tadalafil moderately reduced urethral pressure in healthy women, without affecting voiding parameters. The clinical implications of this are yet to be determined.
Assuntos
Sintomas do Trato Urinário Inferior , Uretra , Feminino , Humanos , Tadalafila/farmacologia , Tadalafila/uso terapêutico , Estudos Cross-Over , Micção , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Método Duplo-Cego , Carbolinas/farmacologia , Carbolinas/uso terapêuticoRESUMO
AIMS: Activation of the endocannabinoid system by monoacylglycerol lipase (MAGL) blockade may affect the lower urinary tract function. We investigated the effect of an MAGL inhibitor, MJN110, on neurogenic lower urinary tract dysfunction (LUTD) in the mouse model of spinal cord injury (SCI). METHODS: Female C57BL/6 mice that underwent spinal cord transection at T8-10 level were divided into three groups consisting of (1) vehicle-treated SCI mice, (2) 5 mg/kg, or (3) 10 mg/kg of MJN110-treated SCI mice. MJN110 and vehicle were administered intraperitoneally for 7 days from 4 weeks after spinal cord transection. We then conducted awake cystometrograms and compared urodynamic parameters between three groups. The expression of cannabinoid (CB) receptors, TRP receptors, and inflammatory cytokines in L6-S1 dorsal root ganglia (DRG) or the bladder mucosa were evaluated and compared among three groups. Changes in the level of serum 2-arachidonoylglycerol (2-AG) and bladder MAGL were also evaluated. RESULTS: In the cystometrogram, detrusor overactivity (DO) parameters, such as the number of nonvoiding contraction (NVC), a ratio of time to the 1st NVC to intercontraction interval (ICI), and NVC integrals were improved by MJN110 treatment, and some effects were dose dependent. Although MJN110 did not improve voiding efficiency, it decreased bladder capacity, ICI, and residual urine volume compared to vehicle injection. MJN110 treatment groups had lower CB2, TRPV1, TRPA1, and inflammatory cytokines mRNA levels in DRG and bladder mucosa. Serum 2-AG was increased, and bladder MAGL was decreased after MAGL inhibitor treatment. CONCLUSIONS: MAGL inhibition improved LUTD including attenuation of DO after SCI. Thus, MAGL can be a therapeutic target for neurogenic LUTD after SCI.
Assuntos
Camundongos Endogâmicos C57BL , Monoacilglicerol Lipases , Traumatismos da Medula Espinal , Bexiga Urinária , Urodinâmica , Animais , Monoacilglicerol Lipases/antagonistas & inibidores , Monoacilglicerol Lipases/metabolismo , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/metabolismo , Feminino , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/fisiopatologia , Urodinâmica/efeitos dos fármacos , Camundongos , Modelos Animais de Doenças , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Gânglios Espinais/fisiopatologia , Receptores de Canabinoides/metabolismo , Receptores de Canabinoides/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Endocanabinoides/metabolismo , Citocinas/metabolismo , Bexiga Urinaria Neurogênica/tratamento farmacológico , Bexiga Urinaria Neurogênica/fisiopatologia , Bexiga Urinaria Neurogênica/etiologia , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Sintomas do Trato Urinário Inferior/fisiopatologia , Sintomas do Trato Urinário Inferior/etiologia , Carbamatos , SuccinimidasRESUMO
PURPOSE: Although it is known that alpha-adrenergic receptor antagonists have positive effects on metabolic parameters such as glucose metabolism, lipid profile, and insulin sensitivity, it is unclear whether this is a class effect. Tamsulosin is reported to have adverse effects on glucose metabolism and insulin resistance, and this may be because of its lack of glycolysis-enhancing effect compared with other alpha-adrenergic receptor antagonists with glycolysis-enhancing effects such as doxazosin, terazosin, and alfuzosin. The aim of this study was to compare the effect of tamsulosin on metabolic parameters with another alpha-1 adrenergic receptor antagonist, doxazosin. METHODS: In this prospective, observational, controlled, 12-week clinical study, a total of 60 male patients aged ≥ 40 years who were first started on tamsulosin (n = 30; 0.4 mg/day, oral; mean age, 59.20 ± 8.97 years) or doxazosin (n = 30; 4 or 8 mg/day, oral; mean age, 58.50 ± 8.93 years) for benign prostatic hyperplasia (BPH) or lower urinary tract symptoms (LUTS) were enrolled. The groups were compared according to the changes in anthropometric and biochemical parameters (glycemia, lipid profile, and insulin sensitivity) at the end of treatment. RESULTS: In intragroup analyses, systolic blood pressure, diastolic blood pressure, total cholesterol, and HbA1c levels decreased significantly in the doxazosin group compared with baseline (p < 0.05 for all), while no significant change was observed in the tamsulosin group. In comparisons between groups, systolic blood pressure, total cholesterol, and low-density lipoprotein cholesterol levels showed a significant decrease in the doxazosin group compared with the tamsulosin group (percent change: - 6.68 ± 13.08 vs. 0.53 ± 11.02, p = 0.025; - 3.63 ± 9.56 vs. 4.02 ± 10.86, p = 0.005; and - 5.62 ± 18.18 vs. 5.24 ± 15.42, p = 0.015, respectively). CONCLUSION: Although these results do not support previous findings that tamsulosin has adverse effects on metabolic parameters, they suggest that doxazosin treatment may be a reason for preference in patients with BPH or LUTS accompanied by metabolic disorder.
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Antagonistas de Receptores Adrenérgicos alfa 1 , Doxazossina , Hiperplasia Prostática , Tansulosina , Humanos , Masculino , Doxazossina/uso terapêutico , Tansulosina/uso terapêutico , Pessoa de Meia-Idade , Estudos Prospectivos , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Hiperplasia Prostática/tratamento farmacológico , Idoso , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Glicemia/metabolismo , Glicemia/efeitos dos fármacos , Resistência à Insulina , Hemoglobinas Glicadas/metabolismo , Sulfonamidas/uso terapêuticoRESUMO
PURPOSE: Patients with suspected UTIs are categorized into 3 clinical phenotypes based on current guidelines: no UTI, asymptomatic bacteriuria (ASB), or UTI. However, all patients may not fit neatly into these groups. Our objective was to characterize clinical presentations of patients who receive urine tests using the "continuum of UTI" approach. MATERIALS AND METHODS: This was a retrospective cohort study of a random sample of adult noncatheterized inpatient and emergency department encounters with paired urinalysis and urine cultures from 5 hospitals in 3 states between January 01, 2017, and December 31, 2019. Trained abstractors collected clinical (eg, symptom) and demographic data. A focus group discussion with multidisciplinary experts was conducted to define the continuum of UTI, a 5-level classification scheme that includes 2 new categories: lower urinary tract symptoms/other urologic symptoms and bacteriuria of unclear significance. The newly defined continuum of UTI categories were compared to the current UTI classification scheme. RESULTS: Of 220,531 encounters, 3392 randomly selected encounters were reviewed. Based on the current classification scheme, 32.1% (n = 704) had ASB and 53% (n = 1614) did not have a UTI. When applying the continuum of UTI categories, 68% of patients (n = 478) with ASB were reclassified as bacteriuria of unclear significance and 29% of patients (n = 467) with "no UTI" were reclassified to lower urinary tract symptoms/other urologic symptoms. CONCLUSIONS: Our data suggest the need to reframe our conceptual model of UTI vs ASB to reflect the full spectrum of clinical presentations, acknowledge the diagnostic uncertainty faced by frontline clinicians, and promote a nuanced approach to diagnosis and management of UTIs.
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Bacteriúria , Sintomas do Trato Urinário Inferior , Infecções Urinárias , Adulto , Humanos , Bacteriúria/diagnóstico , Bacteriúria/tratamento farmacológico , Estudos Retrospectivos , Infecções Urinárias/diagnóstico , Infecções Urinárias/tratamento farmacológico , Urinálise , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Antibacterianos/uso terapêuticoRESUMO
INTRODUCTION: Benign prostatic hyperplasia (BPH), as a clinical entity that affects many people, has always been in the forefront of interest among researchers, pharmaceutical companies, and physicians. Patients with BPH exhibit a diverse range of symptoms, while current treatment options can occasionally cause adverse events. All the aforementioned have led to an increased demand for more effective treatment options. AREAS COVERED: This review summarizes the outcomes of new medications used in a pre-clinical and clinical setting for the management of male lower urinary tract symptoms (LUTS)/BPH and provides information about ongoing trials and future directions in the management of this condition. More specifically, sheds light upon drug categories, such as reductaseadrenoceptor antagonists, drugs interfering with the nitric oxide (NO)/cyclic guanosine monophosphate (GMP) signaling pathway, onabotulinumtoxinA, vitamin D3 (calcitriol) analogues, selective cannabinoid (CB) receptor agonists, talaporfin sodium, inhibitor of transforming growth factor beta 1 (TGF-ß1), drugs targeting the hormonal control of the prostate, phytotherapy, and many more. EXPERT OPINION: Clinical trials are being conducted on a number of new medications that may emerge as effective therapeutic alternatives in the coming years.
Assuntos
Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Humanos , Masculino , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/complicações , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Resultado do TratamentoRESUMO
PURPOSE: To evaluate the efficacy of a single perioperative dose of dexamethasone in reducing postembolization syndrome following prostatic artery embolization. MATERIALS AND METHODS: We conducted a single-center double-blind randomized controlled trial from March 2021 to May 2022 (NCT04588857). Participants were randomized to receive either i.v. 24 mg dexamethasone or saline. The primary outcome measures were temperature, pain, and quality of life in the first 5 days following prostatic artery embolization. Sample size of 60 patients was needed for the assessment of primary outcomes. Participants were followed for 6 months and assessed for a variety of secondary outcome measures including inflammatory markers and lower urinary tract symptoms severity. RESULTS: Due to lack of clinical effect and mild symptoms in the control group, the trial was terminated early. 31 participants (16 dexamethasone vs. 15 control) were enrolled and analyzed. A difference in mean temperature was observed on day 1 (37.23 ± 0.64 °C control vs 36.74 ± 0.41 °C dexamethasone, p = 0.02, 95% CI 0.09-0.89). Difference in pain (score out of 10) was seen only on day 5 (1.48 ± 1.2 control vs. 2.9 ± 2.24 dexamethasone, p = 0.04, 95% CI - 2.78-- 0.04). A difference in C-reactive protein values was observed on day 2 (108 [54-161] mg/l control vs 10 [5-33] mg/l dexamethasone, p < 0.01). No significant differences in other outcomes were observed. No side effects were recorded. CONCLUSIONS: Twenty-four milligrams of dexamethasone bolus is safe but does not reduce postembolization syndrome following prostatic artery embolization.
Assuntos
Dexametasona , Embolização Terapêutica , Próstata , Humanos , Masculino , Método Duplo-Cego , Embolização Terapêutica/métodos , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Próstata/irrigação sanguínea , Idoso , Pessoa de Meia-Idade , Síndrome , Resultado do Tratamento , Sintomas do Trato Urinário Inferior/etiologia , Sintomas do Trato Urinário Inferior/terapia , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Qualidade de Vida , Hiperplasia Prostática/terapia , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêuticoRESUMO
AIMS: This International Consultation on Incontinence-Research Society report aims to summarize the evidence and uncertainties regarding the use of hormone replacement therapy by any route in the management of lower urinary tract symptoms (LUTS) including recurrent urinary tract infections (rUTI), with a review of special considerations for the elderly. Research question proposals to further this field have been highlighted. METHODS: An overview of the existing evidence, guidelines, and consensus regarding the use of topical or systemic estrogens in the management of LUTS. RESULTS: There are currently evidence and recommendations to offer topical estrogens to postmenopausal women with overactive bladder symptoms as well as postmenopausal women with rUTIs. Systemic estrogens however have been shown in a meta-analysis to have a negative effect on LUTS and, therefore are not currently recommended. CONCLUSIONS: Although available evidence and recommendations exist for the use of topical estrogens, few women are commenced on these in primary care. There remain large gaps still within our knowledge of the use of estrogens within the management of LUTS, particularly on when it should be commenced, the length of time treatment should be continued for, and barriers to prescribing.
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Terapia de Reposição de Estrogênios , Sintomas do Trato Urinário Inferior , Pós-Menopausa , Humanos , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Sintomas do Trato Urinário Inferior/fisiopatologia , Feminino , Estrogênios/administração & dosagem , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/diagnósticoAssuntos
Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Masculino , Humanos , Tadalafila/uso terapêutico , Hiperplasia Prostática/complicações , Hiperplasia Prostática/tratamento farmacológico , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Sintomas do Trato Urinário Inferior/etiologia , Sintomas do Trato Urinário Inferior/diagnóstico , Resultado do Tratamento , Método Duplo-CegoRESUMO
BACKGROUND: Clinical practice guidelines recommend testosterone replacement therapy (TRT) for men with sexual dysfunction and testosterone deficiency. However, TRT is commonly promoted in men without testosterone deficiency and existing trials often do not clearly report participants' testosterone levels or testosterone-related symptoms. This review assesses the potential benefits and harms of TRT in men presenting with complaints of sexual dysfunction. OBJECTIVES: To assess the effects of testosterone replacement therapy compared to placebo or other medical treatments in men with sexual dysfunction. SEARCH METHODS: We performed a comprehensive search of CENTRAL (the Cochrane Library), MEDLINE, EMBASE, and the trials registries ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform, with no restrictions on language of publication or publication status, up to 29 August 2023. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in men (40 years or over) with sexual dysfunction. We excluded men with primary or secondary hypogonadism. We compared testosterone or testosterone with phosphodiesterase-5 inhibitors (PDEI5I) to placebo or PDE5I alone. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the literature, assessed the risk of bias, extracted data, and rated the certainty of evidence (CoE) according to GRADE using a minimally contextualized approach. We performed statistical analyses using a random-effects model and interpreted them according to standard Cochrane methodology. Predefined primary outcomes were self-reported erectile dysfunction assessed by a validated instrument, sexual quality of life assessed by a validated instrument, and cardiovascular mortality. Secondary outcomes were treatment withdrawal due to adverse events, prostate-related events, and lower urinary tract symptoms (LUTS). We distinguished between short-term (up to 12 months) and long-term (> 12 months) outcomes. MAIN RESULTS: We identified 43 studies with 11,419 randomized participants across three comparisons: testosterone versus placebo, testosterone versus PDE5I, and testosterone with PDE5I versus PDE5I alone. This abstract focuses on the most relevant comparison of testosterone versus placebo. Testosterone versus placebo (up to 12 months) Based on a predefined sensitivity analysis of studies at low risk of bias, and an analysis combing data from the similar International Index of Erectile Function (IIEF-EF) and IIEF-5 instruments, TRT likely results in little to no difference in erectile function assessed with the IIEF-EF (mean difference (MD) 2.37, 95% confidence interval (CI) 1.67 to 3.08; I² = 0%; 6 RCTs, 2016 participants; moderate CoE) on a scale from 6 to 30 with larger values reflecting better erectile function. We assumed a minimal clinically important difference (MCID) of greater than or equal to 4. TRT likely results in little to no change in sexual quality of life assessed with the Aging Males' Symptoms scale (MD -2.31, 95% CI -3.63 to -1.00; I² = 0%; 5 RCTs, 1030 participants; moderate CoE) on a scale from 17 to 85 with larger values reflecting worse sexual quality of life. We assumed a MCID of greater than or equal to 10. TRT also likely results in little to no difference in cardiovascular mortality (risk ratio (RR) 0.83, 95% CI 0.21 to 3.26; I² = 0%; 10 RCTs, 3525 participants; moderate CoE). Based on two cardiovascular deaths in the placebo group and an assumed MCID of 3%, this would correspond to no additional deaths per 1000 men (95% CI 1 fewer to 4 more). TRT also likely results in little to no difference in treatment withdrawal due to adverse events, prostate-related events, or LUTS. Testosterone versus placebo (later than 12 months) We are very uncertain about the longer-term effects of TRT on erectile dysfunction assessed with the IIEF-EF (MD 4.20, 95% CI -2.03 to 10.43; 1 study, 42 participants; very low CoE). We did not find studies reporting on sexual quality of life or cardiovascular mortality. We are very uncertain about the effect of testosterone on treatment withdrawal due to adverse events. We found no studies reporting on prostate-related events or LUTS. AUTHORS' CONCLUSIONS: In the short term, TRT probably has little to no effect on erectile function, sexual quality of life, or cardiovascular mortality compared to a placebo. It likely results in little to no difference in treatment withdrawals due to adverse events, prostate-related events, or LUTS. In the long term, we are very uncertain about the effects of TRT on erectile function when compared to placebo; we did not find data on its effects on sexual quality of life or cardiovascular mortality. The certainty of evidence ranged from moderate (signaling that we are confident that the reported effect size is likely to be close to the true effect) to very low (indicating that the true effect is likely to be substantially different). The findings of this review should help to inform future guidelines and clinical decision-making at the point of care.
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Doenças Cardiovasculares , Disfunção Erétil , Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Masculino , Humanos , Disfunção Erétil/tratamento farmacológico , Hiperplasia Prostática/complicações , Testosterona/efeitos adversos , Próstata , Sintomas do Trato Urinário Inferior/tratamento farmacológicoRESUMO
AIM: Antimuscarinics and the ß3-adrenoreceptor agonist, mirabegron, are commonly used for treating patients with overactive bladder (OAB) and α1 -adrenoreceptor antagonists (α1 -blockers) are the main pharmacological agents used for treating lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). As these conditions commonly occur together, the aim of this systematic review was to identify publications that compared the use of an α1 -blocker plus mirabegron with an α1 -blocker plus antimuscarinic in men with LUTS secondary to BPH and OAB. A meta-analysis was subsequently conducted to explore the safety and efficacy of these combinations. METHODS: Included records had to be from a parallel-group, randomized clinical trial that was ≥8 weeks in duration. Participants were male with LUTS secondary to BPH and OAB. The indirect analyses that were identified compared an α1 -blocker plus OAB agent with an α1 -blocker plus placebo. The PubMed/Medical Literature Analysis and Retrieval System Online, the Excerpta Medica Database, the Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov registry were searched for relevant records up until March 5, 2020. Safety outcomes included incidences of overall treatment-emergent adverse events (TEAEs) and urinary retention, postvoid residual volume, and maximum urinary flow (Qmax ). Primary efficacy outcomes were micturitions/day, incontinence episodes/day, and urgency episodes/day, and secondary outcomes were Overactive Bladder Symptom Score and International Prostate Symptom Score. A Bayesian network meta-analysis approach was used for the meta-analysis. RESULTS: Out of a total of 1039 records identified, 24 were eligible for inclusion in the meta-analysis. There were no statistically significant differences between the α1 -blocker plus mirabegron and α1 -blocker plus antimuscarinic groups in terms of the comparisons identified for all the safety and efficacy analyses conducted. Numerically superior results were frequently observed for the α1 -blocker plus mirabegron group compared with the α1 -blocker plus antimuscarinic group for the safety parameters, including TEAEs, urinary retention, and Qmax . For some of the efficacy parameters, most notably micturitions/day, numerically superior results were noted for the α1 -blocker plus antimuscarinic group. Inconsistency in reporting and study variability were noted in the included records, which hindered data interpretation. CONCLUSION: This systematic review and meta-analysis showed that an α1 -blocker plus mirabegron and an α1 -blocker plus antimuscarinic have similar safety and efficacy profiles in male patients with LUTS secondary to BPH and OAB. Patients may, therefore, benefit from the use of either combination within the clinical setting.
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Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Tiazóis , Bexiga Urinária Hiperativa , Retenção Urinária , Humanos , Masculino , Feminino , Bexiga Urinária Hiperativa/tratamento farmacológico , Bexiga Urinária Hiperativa/etiologia , Bexiga Urinária Hiperativa/diagnóstico , Antagonistas Muscarínicos/efeitos adversos , Hiperplasia Prostática/complicações , Hiperplasia Prostática/tratamento farmacológico , Retenção Urinária/complicações , Teorema de Bayes , Metanálise em Rede , Resultado do Tratamento , Quimioterapia Combinada , Acetanilidas/efeitos adversos , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Sintomas do Trato Urinário Inferior/etiologia , Agonistas de Receptores Adrenérgicos beta 3/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
PURPOSE: To compare the efficacy and the safety of Tamsulosin 0.4 mg/day and 0.8 mg/day in patients suffering from lower urinary tract symptoms due to benign prostatic obstruction. PATIENTS AND METHODS: A prospective interventional, double-blinded, controlled study was carried out on 93 patients who met the criteria and divided randomly into two groups: group A for Tamsulosin 0.4 mg/day and group B for Tamsulosin 0.8 mg/day. International prostate symptom score, post void residual urine volume, and maximum flow rate of urine were assessed before and after 4 weeks of treatment. RESULTS: Both study groups showed a significant reduction in storage sub-score but only frequency was significantly reduced in group B (P < 0.001). On the other hand, Tamsulosin 0.8 mg was superior to Tamsulosin 0.4 mg regarding voiding sub-score except for straining (P = 0.325). Accordingly, the total international prostate symptom score was significantly improved in group B versus group A (P < 0.001). Furthermore, maximum flow rate and post-void residual urine volume were notably improved in Group B as compared to Group A (P < 0.001). Of all adverse events only dizziness was noted to be statistically significant in Group B versus Group A (P < 0.001). CONCLUSION: Tamsulosin 0.8 mg has shown better outcomes in treating patients who suffer from lower urinary tract symptoms due to benign prostatic enlargement than Tamsulosin 0.4 mg, and besides that, it is well tolerated. TRIAL REGISTRATION NUMBER: M S 292/2020, SID: 373, date: 22/4/2020.
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Antagonistas de Receptores Adrenérgicos alfa 1 , Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Tansulosina , Humanos , Tansulosina/uso terapêutico , Tansulosina/administração & dosagem , Masculino , Hiperplasia Prostática/complicações , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Sintomas do Trato Urinário Inferior/etiologia , Estudos Prospectivos , Método Duplo-Cego , Pessoa de Meia-Idade , Idoso , Antagonistas de Receptores Adrenérgicos alfa 1/administração & dosagem , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: There is limited research into the efficacy and safety of tadalafil combined with tamsulosin for the treatment of lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH), with or without erectile dysfunction (ED). Therefore, we aimed to investigate the efficacy and safety of combination therapy compared to that of monotherapy. METHODS: We searched PubMed, Embase, Cochrane Library, Web of Science, SinoMed, CNKI, WanFang Data Service Platform, and