British Association of Urological Surgeons Consensus statements on the management of ketamine uropathy.

OBJECTIVES: To provide guidance in the form of consensus statement in the management of ketamine uropathy. METHODS: A literature review of ketamine uropathy was performed. The consensus method was of a modified nominal group technique and has been use in the previous British Association of Urological Surgeons (BAUS) consensus documents and was led by the Female, Neurological and Urodynamic Urology Section of the BAUS. RESULTS: A number of consensus statements detailing the assessment and management of urological complications relate to the recreational use of ketamine (ketamine uropathy) in both elective and emergency urology settings. CONCLUSION: Comprehensive management pathway for ketamine-related urinary tract dysfunction and uropathy has been detailed.

Ketamine uropathy: Clinical experience in a high prevalence center.

OBJECTIVES: Ketamine uropathy causes inflammatory changes to the urothelium, manifesting as significant lower urinary tract symptoms, small bladder capacity, and pelvic pain. Upper tract involvement and hydronephrosis can occur. Data from UK centers are limited, and no formal treatment guidelines exist. PATIENTS AND METHODS: All patients with ketamine uropathy presenting to our unit over an 11-year period were identified through operative and clinic lists, emergency presentations, and a prospectively collected local database. Demographic data, biochemical findings, imaging techniques, and both medical and surgical management were recorded. RESULTS: A total of 81 patients with ketamine uropathy were identified from 2011 to 2022; however, a large proportion presented from 2018 onwards. The average age at presentation was 26 years (interquartile range [IQR]: 27-34), 72.8% were male, and average follow-up time was 34 months (IQR: 8-46). Therapeutic interventions included anticholinergic medication, cystodistension, and intravesical sodium hyaluronate. Hydronephrosis was present in 20 (24.7%) patients and nephrostomy insertion was required in six. One patient underwent bladder augmentation surgery. Serum gamma-glutamyl transferase and length of follow-up were significantly higher in patients with hydronephrosis. Adherence to follow-up was poor. CONCLUSIONS: We present a large cohort of patients with ketamine uropathy from a small town in the UK which is unusual. The incidence appears to be rising, in-keeping with increasing recreational ketamine use and should be of concern to urologists. Abstinence is a key aspect of management, and a multi-disciplinary approach works best particularly as many patients are lost to follow-up. The development of formal guidance would be helpful.

Systematic review and meta-analysis of ketamine-associated uropathy.

INTRODUCTION: This systematic review and meta-analysis focused on the literature regarding ketamine-associated uropathy to summarise its clinical manifestations, the results of urological assessments, and current management. METHODS: A literature search was conducted using keywords and MeSH terms related to ketamine abuse, urinary tracts, and urological examinations. Databases including Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched up to 26 June 2020. RESULTS: In total, 1365 articles were retrieved; 45 articles (4921 patients) were included in the analysis of patient demographics, clinical manifestations, examination results, and treatments. Frequency was the most common manifestation (pooled prevalence 77.1%, 95% confidence interval [CI]=56.9%-92.2%), followed by urgency (69.9%, 95% CI=48.8%-87.3%) and suprapubic pain (60.4%, 95% CI=35.3%-82.9%). Upper urinary tract involvement was less common; the pooled prevalence of hydronephrosis was 30.2% (95% CI=22.0%-39.2%). Further workup revealed a pooled functional bladder capacity of 95.23 mL (95% CI=63.57-126.88 mL), pooled voided volume of 113.31 mL (95% CI=59.44- 167.19 mL), and pooled maximum urine flow rate of 8.69 mL/s (95% CI=5.54-11.83 mL/s). Cystoscopic examinations and bladder biopsy revealed frequent urothelial denudation, inflammatory changes, and inflammatory cell infiltration. Treatments included oral medications for symptomatic relief, intravesical therapy, and surgery (eg, hydrodistension and bladder reconstruction), but ketamine abstinence was necessary for improvement. CONCLUSION: Ketamine-associated uropathy frequently involves frequency, urgency, and suprapubic pain; upper urinary tract involvement is less common. Affected patients showed reductions in bladder capacity and urine flow rate. Endoscopic and histological analyses often revealed cystitis. Despite variations in treatment, ketamine abstinence is important for all patients with ketamine-associated uropathy.

Evolving Role of Silodosin for the Treatment of Urological Disorders - A Narrative Review.

Use of α-androgenic receptor blockers remains a mainstay therapeutic approach for the treatment of urological diseases. Silodosin is recommended over other α-blockers for the treatment of lower urinary tract symptoms (LUTS) and benign prostate hyperplasia (BPH), due to its high α1A uroselectivity. Current research data suggest that silodosin is efficacious in the management of various urological diseases. Thus, we herein review the current evidence of silodosin related to its efficacy and tolerability and appraise the available literature that might ultimately aid in management of various urological conditions at routine clinical practice. Literature reveals that silodosin is beneficial in improving nocturia events related to LUTS/BPH. Silodosin exerts effect on relaxing muscles involved in detrusor obstruction, therefore prolonging the need for patients undergoing invasive surgery. Silodosin treatment, either as a monotherapy or combination, significantly improves International Prostate Symptom Score (IPSS) including both storage and voiding symptoms in patients with BPH/LUTS. Patients on other treatment therapies such as phosphodiesterase 5 inhibitors or other α-blockers are well managed with this drug. Steadily, silodosin has proved beneficial in the treatment of other urological disorders such as chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), overactive bladder/acute urinary retention (AUR), premature ejaculation (PE), and prostate cancer post brachytherapy-induced progression. In patients with distal ureteral stones, silodosin treatment is beneficial in decreasing stone expulsion time without affecting stone expulsion rate or analgesic need. Moreover, there were significant improvements in intravaginal ejaculation latency time, quality of life scores, and decrease in PE profile among patients with PE. Silodosin has also demonstrated promising results in increasing the likelihood of successful trial without catheter in patients with AUR and those taking antihypertensive drugs. Reports from Phase II studies have shown promising role of silodosin in the treatment of CP/CPPS as well as facilitating ureteral stone passage. From the robust data in this review, further silodosin treatment strategies in the management of different urological conditions need to be focused on.

Bisphenol-A analogs induce lower urinary tract dysfunction in male mice.

Bisphenol-A (BPA), an estrogenic endocrine disrupting chemical, significantly impacts numerous diseases and abnormalities in mammals. Estrogens are known to play an important role in the biology of the prostate; however, little is known about the role of bisphenols in the etiology of prostate pathologies, including benign prostate hyperplasia (BPH) and associated lower urinary tract dysfunction (LUTD). Bisphenol-F (BPF) and bisphenol-S (BPS) are analogs often used as substitutes for BPA; they are both reported to have in vitro and in vivo estrogenic effects similar to or more potent than BPA. The objective of this study was to assess the role of these bisphenols in the development of LUTD in adult male mice. In adult mice exposed to BPA, BPS or BPF, we examined urinary tract histopathology and physiological events associated with urinary dysfunction. Mice treated with bisphenols displayed increased bladder (p < 0.005) and prostate (p < 0.0001) mass, and there was an increased number of prostatic ducts in the prostatic urethra (p < 0.05) and decreased size of the urethra lumen (p < 0.05) compared to negative controls. After two months of bisphenol exposure, mice displayed notable differences in cystometric tracings compared to controls, consistent with LUTD. Treatment of male mice with all bisphenols also induced voiding dysfunction manifested by detrusor instability and histologic changes in the prostatic urethra of male rodents, consistent with LUTD. Our results implicate BPA and its replacements in the development and progression LUTD in mice and provide insights into the development and progression of BPH/LUTS in men.

Low Rates of Urologic Side Effects Following Coronavirus Disease Vaccination: An Analysis of the Food and Drug Administration Vaccine Adverse Event Reporting System.

OBJECTIVE: To quantify and describe urologic adverse events and symptoms after vaccination with the Pfizer-BioNTech and Moderna COVID-19 vaccines. METHODS AND MATERIALS: We queried the FDA Vaccine Adverse Event Reporting System (VAERS) for all reported symptoms following the Pfizer-BioNTech and Moderna vaccines as of February 12th, 2021. All urologic symptoms were isolated and the reported adverse events associated with each symptom were reviewed. RESULTS: Out of 15,785 adverse event reports, only 0.7% (113) described urologic symptoms. A total of 156 urologic symptoms were described amongst the 113 adverse event reports. The Pfizer-BioNTech vaccine was responsible for 61% of these reports and the Moderna vaccine was responsible for 39%. These symptoms were grouped into five different categories: Lower Urinary Tract Symptoms (n = 34, 22%), Hematuria (n = 22, 14%), Urinary Infection (n = 41, 26%), Skin and/or Soft Tissue (n = 16, 10%), and Other (n = 43, 28%). The median age of the patients reporting urologic symptoms was 63 years (IQR 44-79, Range: 19-96) and 54% of the patients were female. CONCLUSION: Urologic symptoms reported after COVID-19 vaccination are extremely rare. Given the common prevalence of many of these reported symptoms in the general population, there does not appear to be a correlation between vaccination and urologic symptoms, but as the vaccination criteria expands, further monitoring of the Vaccine Adverse Event Reporting System is needed.

Abdominal Imaging Manifestations of Recreational Drug Use.

Recreational drug use is a burgeoning health issue worldwide, with a variety of presenting symptoms and complications. These complications can be secondary to the toxic effects of the drug itself, drug impurities, and nonsterile injection. The abdominal radiologist is likely to encounter patients who use drugs recreationally and may be responsible for recognizing and reporting these acute conditions, which in some cases can be life threatening. Because these patients often present with an altered mental state and may deny or withhold information on drug use, the underlying cause may be difficult to determine. The most commonly used drugs worldwide include cocaine, cannabinoids, opioids, and amphetamines and their derivatives. Complications of use of these drugs that can be seen at abdominopelvic CT can involve multiple organ systems, including the soft tissue and gastrointestinal, genitourinary, vascular, and musculoskeletal systems. A diverse range of abdominal complications associated with these drugs can be seen at imaging, including disseminated infections, gastrointestinal ischemia, and visceral infarction. Radiologists should be familiar with the imaging findings of these complications to accurately diagnose these entities and help guide workup and patient treatment. ©RSNA, 2020.

Evaluation of the efficacy and safety of deferiprone compared with deferasirox in paediatric patients with transfusion-dependent haemoglobinopathies (DEEP-2): a multicentre, randomised, open-label, non-inferiority, phase 3 trial.

BACKGROUND: Transfusion-dependent haemoglobinopathies require lifelong iron chelation therapy with one of the three iron chelators (deferiprone, deferasirox, or deferoxamine). Deferasirox and deferiprone are the only two oral chelators used in adult patients with transfusion-dependent haemoglobinopathies. To our knowledge, there are no randomised clinical trials comparing deferiprone, a less expensive iron chelator, with deferasirox in paediatric patients. We aimed to show the non-inferiority of deferiprone versus deferasirox. METHODS: DEEP-2 was a phase 3, multicentre, randomised trial in paediatric patients (aged 1 month to 18 years) with transfusion-dependent haemoglobinopathies. The study was done in 21 research hospitals and universities in Italy, Egypt, Greece, Albania, Cyprus, Tunisia, and the UK. Participants were receiving at least 150 mL/kg per year of red blood cells for the past 2 years at the time of enrolment, and were receiving deferoxamine (<100 mg/kg per day) or deferasirox (<40 mg/kg per day; deferasirox is not registered for use in children aged <2 years so only deferoxamine was being used in these patients). Any previous chelation treatment was permitted with a 7-day washout period. Patients were randomly assigned 1:1 to receive orally administered daily deferiprone (75-100 mg/kg per day) or daily deferasirox (20-40 mg/kg per day) administered as dispersible tablets, both with dose adjustment for 12 months, stratified by age (<10 years and ≥10 years) and balanced by country. The primary efficacy endpoint was based on predefined success criteria for changes in serum ferritin concentration (all patients) and cardiac MRI T2-star (T2*; patients aged >10 years) to show non-inferiority of deferiprone versus deferasirox in the per-protocol population, defined as all randomly assigned patients who received the study drugs and had available data for both variables at baseline and after 1 year of treatment, without major protocol violations. Non-inferiority was based on the two-sided 95% CI of the difference in the proportion of patients with treatment success between the two groups and was shown if the lower limit of the two-sided 95% CI was greater than -12·5%. Safety was assessed in all patients who received at least one dose of study drug. This study is registered with EudraCT, 2012-000353-31, and ClinicalTrials.gov, NCT01825512. FINDINGS: 435 patients were enrolled between March 17, 2014, and June 16, 2016, 393 of whom were randomly assigned to a treatment group (194 to the deferiprone group; 199 to the deferasirox group). 352 (90%) of 390 patients had ß-thalassaemia major, 27 (7%) had sickle cell disease, five (1%) had thalassodrepanocytosis, and six (2%) had other haemoglobinopathies. Median follow-up was 379 days (IQR 294-392) for deferiprone and 381 days (350-392) for deferasirox. Non-inferiority of deferiprone versus deferasirox was established (treatment success in 69 [55·2%] of 125 patients assigned deferiprone with primary composite efficacy endpoint data available at baseline and 1 year vs 80 [54·8%] of 146 assigned deferasirox, difference 0·4%; 95% CI -11·9 to 12·6). No significant difference between the groups was shown in the occurrence of serious and drug-related adverse events. Three (2%) cases of reversible agranulocytosis occurred in the 193 patients in the safety analysis in the deferiprone group and two (1%) cases of reversible renal and urinary disorders (one case of each) occurred in the 197 patients in the deferasirox group. Compliance was similar between treatment groups: 183 (95%) of 193 patients in the deferiprone group versus 192 (97%) of 197 patients in the deferisirox group. INTERPRETATION: In paediatric patients with transfusion-dependent haemoglobinopathies, deferiprone was effective and safe in inducing control of iron overload during 12 months of treatment. Considering the need for availability of more chelation treatments in paediatric populations, deferiprone offers a valuable treatment option for this age group. FUNDING: EU Seventh Framework Programme.

Impact of Anemia on the Risk of Bleeding Following Percutaneous Coronary Interventions in Patients ≥75 Years of Age.

Bleeding risk stratification is an unresolved issue in older adults. Anemia may reflect subclinical blood losses that can be exacerbated after percutaneous coronary intervention . We sought to prospectively determine the contribution of anemia to the risk of bleeding in 448 consecutive patients aged 75 or more years, treated by percutaneous coronary interventions without concomitant indication for oral anticoagulation. We evaluated the effect of WHO-defined anemia on the incidence of 1-year nonaccess site-related major bleeding. The prevalence of anemia was 39%, and 13.1% of anemic and 5.2% of nonanemic patients suffered a bleeding event (hazard ratio 2.75, 95% confidence interval 1.37 to 5.54, p = 0.004). Neither PRECISE-DAPT nor CRUSADE scores were superior to hemoglobin for the prediction of bleeding. In conclusion, anemia is a powerful predictor of bleeding with potential utility for simplifying tailoring therapies.

Dysuria due to benign prostatic hyperplasia of the median lobe with ketamine-associated uropathy in a young male.

BACKGROUND: Benign prostatic hyperplasia (BPH) rarely occurs in children or young males. In this case report, a 29-year-old male patient diagnosed with BPH coexisting with ketamine-associated uropathy was reported to investigate the possible relationship between BPH and ketamine-associated uropathy as well as therapeutic strategies. CASE PRESENTATION: A 29-year-old male patient with a 3-year history of ketamine inhalation, complaining of dysuria with frequency and urgency, was admitted. Hydronephrosis, hydroureters, uneven bladder wall thickening and a tumour located in the outlet of the bladder were detected with computed tomography (CT). The patient agreed to cystoscopy under general anaesthesia. A spherical tumour with a diameter of approximately 2 cm was found to originate from the median lobe of the prostate and follicular lesions were diffusely distributed on the right bladder wall. The tumour and follicular lesions in the bladder were resected successfully, and pathology demonstrated BPH and chronic inflammation of the mucous membranes separately. The patient quit ketamine completely during the one-year follow-up. Dysuria was relieved completely and no tumour or follicular neoplasm recurrence was found. CONTRIBUTION: Inflammation in the urothelium, as a direct or indirect consequence of ketamine, may contribute to the development of BPH. Both surgical interventions to remove obstruction and ketamine cessation are necessary approaches.

Management of complications of ketamine abuse: 10 years' experience in Hong Kong.

Ketamine is an N-methyl-d-aspartate receptor antagonist, a dissociative anaesthetic agent and a treatment option for major depression, treatment-resistant depression, and bipolar disorder. Its strong psychostimulant properties and easy absorption make it a favourable candidate for substance abuse. Ketamine entered Hong Kong as a club drug in 2000 and the first local report of ketamine-associated urinary cystitis was published in 2007. Ketamine-associated lower-urinary tract symptoms include frequency, urgency, nocturia, dysuria, urge incontinence, and occasionally painful haematuria. The exact prevalence of ketamine-associated urinary cystitis is difficult to assess because the abuse itself and many of the associated symptoms often go unnoticed until a very late stage. Additionally, upper-urinary tract pathology, such as hydronephrosis, and other complications involving neuropsychiatric, hepatobiliary, and gastrointestinal systems have also been reported. Gradual improvement can be expected after abstinence from ketamine use. Sustained abstinence is the key to recovery, as relapse usually leads to recurrence of symptoms. Both medical and surgical management can be used. The Youth Urological Treatment Centre at the Prince of Wales Hospital, Hong Kong, has developed a four-tier treatment protocol with initial non-invasive investigation and management for these patients. Multidisciplinary care is essential given the complex and diverse psychological factors and sociological background that underlie ketamine abuse and abstinence status.

Histopathological characteristics of ketamine-associated uropathy and their clinical association.

AIM: To investigate the histopathological findings in ketamine-associated uropathy (KU) and their clinical association. METHODS: Thirty-eight KU patients had received history investigation and video urodynamic study. Twelve of them were clinically mild KU who were admitted for cystoscopic hydrodistention. The other 26 patients were severe KU who were admitted for enterocystoplasty with or without ureter reimplantation. Bladder and ureter specimens were harvested during operation, and a single pathologist reviewed all specimens under hematoxylin and eosin stain. The severity of histopathological findings was graded with a 4-point scale (0: none, 1: mild, 2: moderate, and 3: severe) RESULTS: Inflammatory cells infiltrations and nerve hyperplasia were found in the mucosa, muscle, and subserosal layers of KU bladders and ureter. In the mild KU bladder mucosa, the predominant component of the infiltrating inflammatory cells was lymphocytes. In contrast, neutrophils, eosinophils, lymphocytes, and plasma cells infiltration were noted in the mucosa of almost all severe KU bladders. Clinical severe KU was significantly correlated with severe to moderate lymphocytes, plasma cells, neutrophils, eosinophils infiltration, and nerve hyperplasia in bladder mucosa. KU patients with moderate or severe neutrophils or lymphocytes infiltration in bladder mucosa had significantly more severe bladder pain and smaller bladder capacity. CONCLUSION: The histological findings of KU showed whole-layer inflammation and nerve hyperplasia in bladder mucosa. The severity of inflammatory cell infiltration in the bladder mucosa is associated with clinical symptoms. A histopathological examination might be a useful tool to discriminate the KU severity in patients.

Clinical pattern and prevalence of upper gastrointestinal toxicity in patients abusing ketamine.

OBJECTIVE: Evaluations of upper gastrointestinal toxicity from ketamine abuse are uncommon. This study investigated the clinical pattern of upper gastrointestinal symptoms in patients inhaling ketamine. METHODS: In a cross-sectional study of 611 consecutive patients who were seeking treatment for ketamine uropathy in a tertiary hospital setting between August 2008 and June 2016, their clinical pattern of upper gastrointestinal symptoms was evaluated and compared with a control population of 804 non-users. RESULTS: A total of 168 (27.5%) patients abusing ketamine (mean age 26.3 years, 58.9% female) reported the presence of upper gastrointestinal symptoms. These symptoms were significantly more prevalent in patients inhaling ketamine than in those who were not (27.5% vs 5.2%, P < 0.001). Their mean duration of ketamine abuse before symptom presentation was 5.0 ± 3.1 years. The presenting symptoms included epigastric pain (n = 155, 25.4%), recurrent vomiting (n = 48, 7.9%), anemia (n = 36, 5.9%) and gastrointestinal bleeding (n = 20, 3.3%). Uropathy symptoms were preceded by upper gastrointestinal symptoms for 4.4 ± 3.0 years in 141 (83.9%) patients. Logistic regression showed that elder age (odds ratio [OR] 1.06, P = 0.04), active abuser status (OR 1.60, P = 0.04) and longer duration of ketamine abuse (OR 1.00, P = 0.04) were independent factors associated with upper gastrointestinal toxicity. CONCLUSIONS: Although epigastric symptoms are unusual in the young population, upper gastrointestinal toxicity was highly prevalent in those inhaling ketamine. Enquiries about ketamine abuse are recommended when assessing young patients with epigastric symptoms.

[Side effects of pain therapy : Sufficient analgesia without unnecessary complications]. / Nebenwirkungen der Schmerztherapie : Suffiziente Analgesie mit vermeidbaren Komplikationen.

Interventions of acute and chronic pain treatment are associated with risks. Therefore, it is important to know about treatment side effects in order to avoid unnecessary complications and therapy interruption. This knowledge, however, is not to prevent/abandon this treatment altogether. Rather, it is intended to use pain treatment interventions rationally. The following article is to deepen the knowledge of unintended effects of analgetic treatments. Moreover, it will help find an optimal pain therapy in terms of efficacy and tolerable risks as well as limitations. Nonopiates have organ toxic side effects. It is imperative to observe the maximum daily dose and comorbidity. Opioids can have either central or peripheral side effects. Patients suffer, among others, from addiction, breath depression, and tolerance as well as from obstipation, concentration disorders, and an increased risk of falling. Psychiatric drugs, corticosteroids, ketamine, bisphosphonates, and lidocaine are co-analgetics. Besides adverse effects connected to their specific substances, these drugs have partially additive effects on complications of classic analgetics (e. g., gastrointestinal ulceration, renal insufficiency, constipation, and concentration deficits). Invasive procedures (such as epidural catheter) call for an interdisciplinary collaboration. To know about unintended effects helps to avoid dramatic complications (e. g., paraplegia). A sufficient pain therapy, therefore, is more than sufficient analgesia. It also includes the reduction of side effects and complications.

E-cigarettes and Urologic Health: A Collaborative Review of Toxicology, Epidemiology, and Potential Risks.

CONTEXT: Use of electronic cigarettes (ECs) is on the rise in most high-income countries. Smoking conventional cigarettes is a known risk factor for urologic malignancy incidence, progression, and mortality, as well as for other urologic health indicators. The potential impact of EC use on urologic health is therefore of clinical interest to the urology community. OBJECTIVE: To review the available data on current EC use, including potential benefits in urologic patients, potential issues linked to toxicology of EC constituents, and how this might translate into urologic health risks. EVIDENCE ACQUISITION: A Medline search was carried out in August 2016 for studies reporting urologic health outcomes and EC use. Snowballing techniques were also used to identify relevant studies from recent systematic reviews. A narrative synthesis of data around EC health outcomes, toxicology, and potential use in smoking cessation and health policy was carried out. EVIDENCE SYNTHESIS: We found no studies to date that have been specifically designed to prospectively assess urologic health risks, even in an observational setting. Generating such data would be an important contribution to the debate on the role of ECs in public health and clinical practice. There is evidence from a recent Cochrane review of RCTs that ECs can support smoking cessation. There are emerging data indicating that potentially harmful components of ECs such as tobacco-specific nitrosamines, polyaromatic hydrocarbons, and heavy metals could be linked to possible urologic health risks. CONCLUSIONS: ECs might be a useful tool to encourage cessation of conventional cigarette smoking. However, data collection around the specific impact of ECs on urologic health is needed to clarify the possible patient benefits, outcomes, and adverse events. PATIENT SUMMARY: While electronic cigarettes might help some people to stop smoking, their overall impact on urologic health is not clear.

Clinical Significance of Hematuria in Atrial Fibrillation With Oral Anticoagulation Therapy.

BACKGROUND: Hematuria is a common and important complication in atrial fibrillation (AF) patients on oral anticoagulation therapy (OAT). This study evaluated the clinical significance of hematuria and its relationship with genitourinary disease in AF patients receiving OAT.Methods and Results:Among 20,456 consecutive AF patients who visited a tertiary hospital from January 2005 to April 2015, 5,833 had hematuria. Of these 5,833 patients, 3,798 were on OAT (OAT(+) group) and 2,035 were not (OAT(-) group). A total of 1,785 patients from each group were then matched on propensity score analysis. The prevalence of cancer and other diseases in the genitourinary tract was evaluated. While there was no difference in the prevalence of genitourinary stones or urinary tract infection, genitourinary cancer was significantly more common in the OAT(+) group than in the OAT(-) group (1.6% vs. 0.7%, P=0.011). Bladder cancer was the most common genitourinary malignancy, and it was significantly more common in the OAT(+) group (1.2% vs. 0.5%, P=0.019). Subjects on warfarin were more likely to have bladder cancers of lower pathologic grade (63.6% vs. 33.3%, P=0.124). CONCLUSIONS: OAT was associated with a higher prevalence and early detection of genitourinary cancer in AF patients with hematuria. Meticulous evaluation of the cause of hematuria is necessary in AF patients with hematuria receiving OAT.

Adverse urinary effects of allopurinol in dogs with leishmaniasis.

OBJECTIVE: The objective of this study was to describe the adverse effects of allopurinol on the urinary system during treatment of canine leishmaniasis. METHODS: Retrospective case series of 42 dogs that developed xanthinuria while receiving allopurinol treatment for leishmaniasis. RESULTS: Of 320 dogs diagnosed with leishmaniasis, 42 (13%) developed adverse urinary effects. Thirteen (of 42) dogs (31%) developed xanthinuria, renal mineralisation and urolithiasis; 11 (26·2%) showed xanthinuria with renal mineralisation; 9 (21·4%) had xanthinuria with urolithiasis and 9 (21·4%) developed xanthinuria alone. Urinary clinical signs developed in 19 dogs (45·2%). CLINICAL SIGNIFICANCE: This study demonstrates that urolithiasis and renal mineralisation can occur in dogs receiving allopurinol therapy. Dogs receiving therapy should be monitored for the development of urinary adverse effects from the beginning of treatment.

[Influence of drugs on urological diseases]. / Einfluss von Medikamenten auf urologische Krankheiten.

A number of drugs prescribed for the treatment of various diseases can induce urological symptoms as side effects. Antihypertensive drugs (particularly alpha blockers) can result in stress incontinence, whereas selective serotonin reuptake inhibitors (SSRI) can cause urge incontinence and estrogen promotes both forms. A wide range of drugs with anticholinergic activity, among them neuroleptics, tricyclic antidepressants and certain drugs used in airway disorders are associated with urinary retention. Only very few drugs bear a relevant risk for urolithiasis, i. e. the diuretic triamterene and protease inhibitors, such as indinavir; however, the widely used combination of calcium and vitamin D supplementation for prevention of osteoporosis may be an underdiagnosed cause of renal calculi. Drug-induced sexual dysfunction is a frequent side effect of antihypertensive treatment, particularly with beta adrenoceptor blockers and diuretics. The SSRI and some neuroleptics can also impair sexual function.

Clinical staging of ketamine-associated urinary dysfunction: a strategy for assessment and treatment.

PURPOSE: To describe a clinical staging method linked to stepwise treatment indications for ketamine-associated urinary dysfunction (KAUD) based on review of our experience in management of KAUD patients and analysis of their clinical features. METHODS: The eighty-one KAUD patients hospitalized from January 2008 to June 2014 were studied retrospectively. According to ketamine history, renal and liver function, bladder change and up urinary tract involvement, patients were categorized into a described model of three stages. Discriminant analysis was applied to validate the model. The void volume, micturition interval, nocturnal void frequency and pelvic pain and urgency/frequency (PUF) questionnaire score were, respectively, compared after treatments. RESULTS: There were, respectively, 24, 47 and 10 patients in three stages. The duration of abuse varied (p = 0.047) correlated with clinical stages (p = 0.015, r = 0.268). The severity of LUTS was not significant. The creatinine, estimated glomerular filtration rate and liver function were worse in higher stages (p < 0.01), and the incidence of ureteral change and hydronephrosis was greater (p < 0.001). Based on the model, cross-validation confirmed 83.1 % cases were classified correctly. Twenty-four patients in stage I were treated with behavioral modification and pharmacotherapy, thirty-five patients in stage II with hydrodistention and six patients in stage III with surgical intervention due to rapid progression after conservative therapy. All patients in three stages demonstrated improvements in void volume, micturition interval, nocturnal void frequency and PUF score (all p < 0.05) after treatment. CONCLUSION: Clinical staging could serve for assessment of progression, and the staging-based treatment is effective. This model still awaits further validation.

Efficacy and safety of canagliflozin when used in conjunction with incretin-mimetic therapy in patients with type 2 diabetes.

AIMS: To assess the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes enrolled in the CANagliflozin cardioVascular Assessment Study (CANVAS) who were on an incretin mimetic [dipeptidyl peptidase-4 (DPP-4) inhibitor or glucagon-like peptide-1 (GLP-1) receptor agonist]. METHODS: CANVAS is a double-blind, placebo-controlled study that randomized participants to canagliflozin 100 or 300 mg or placebo added to routine therapy. The present post hoc analysis assessed the efficacy and safety of canagliflozin 100 and 300 mg compared with placebo in subsets of patients from CANVAS who were taking background DPP-4 inhibitors or GLP-1 receptor agonists with or without other antihyperglycaemic agents at week 18. RESULTS: Of the 4330 patients in CANVAS, 316 were taking DPP-4 inhibitors and 95 were taking GLP-1 receptor agonists. At 18 weeks, canagliflozin 100 and 300 mg provided larger placebo-subtracted reductions in glycated haemoglobin (HbA1c) in patients taking DPP-4 inhibitors [-0.56% (95% confidence interval [CI]: -0.77, -0.35), and -0.75% (95% CI: -0.95, -0.54), respectively] and GLP-1 receptor agonists [-1.00% (95% CI: -1.35, -0.65), and -1.06% (95% CI: -1.43, -0.69), respectively]. Body weight and blood pressure (BP) reductions were seen with canagliflozin versus placebo in both subsets. Higher incidences of genital mycotic infections and osmotic diuresis-related adverse events (AEs) were seen with canagliflozin compared with placebo. The incidence of hypoglycaemia was numerically higher with canagliflozin versus placebo; nearly all events occurred in patients on background insulin or insulin secretagogues. CONCLUSIONS: In patients on background incretin mimetics, canagliflozin improved HbA1c, body weight and BP, with an increased incidence of AEs related to SGLT2 inhibition.