Outcomes of alpha-blockers as medical expulsive therapy following shockwave lithotripsy: a systematic review and meta-analysis.

OBJECTIVES: To determine stone-free rate following shockwave lithotripsy (SWL) with/without alpha-blockers as well as complication rates (individual and classified using the Clavien-Dindo system). MATERIALS AND METHODS: We performed a systematic review of all randomized controlled trials that included more than 20 patients (age > 18 years) and examined the use of alpha-blockers after SWL. Meta-analysis was performed using 'metafor' in R. We report risk ratios (RRs) with 95% confidence intervals (95% CIs). The PROSPERO ID for the trial was: CRD42021248108. RESULTS: We assessed 158 full-text articles and included a total of 21 studies in our review. There were 1445 patients receiving alpha-blockers and 1478 control patients. Those receiving alpha-blockers were significantly more likely to be stone-free (RR 1.12, 95% CI 1.07-1.16; P < 0.001). This effect was robust to 'trim-and-fill' adjustment. In those taking alpha-blockers there was a significant reduction in Clavien III-V complications and, on trim-and-fill adjustment, a significant reduction in Clavien I-II complications. There were also significant reduction in rates of steinstrasse, pain and requirement for auxiliary procedures. There was no significant difference in retreatment rates. These effects were robust to trim-and-fill adjustment. CONCLUSIONS: There is a modest increase in stone-free rates in those receiving alpha-blockers following SWL, with a reciprocal modest risk reduction for steinstrasse, pain and auxiliary procedures. However, alpha-blockers do not reduce the risk of requiring retreatment.

Does pre-stenting influence outcomes of shockwave lithotripsy? A systematic review and meta-analysis.

OBJECTIVE: To determine whether preoperative use of JJ stents in patients undergoing shockwave lithotripsy (SWL) impacts on stone clearance and the rate of postoperative complications. PATIENTS AND METHODS: We screened multiple databases from inception to January 2021, using the relevant search terms for SWL in patients with a preoperative stent. Inclusion criteria were randomised controlled trials of ≥20 patients aged >18 years who had had SWL with a JJ stent. This review has been registered in the International Prospective Register of Systematic Reviews (PROSPERO; registration number CRD42023443195). Statistical analysis was performed using 'meta' in R. RESULTS: There were seven eligible studies (403 patients receiving JJ stents and 394 controls). There was no significant difference in the stone-free rate (SFR) following SWL with a JJ stent compared to SWL alone. When considering the complication rates, there was a significantly reduced risk of steinstrasse in patients with a JJ stent. However, there was no significant difference in the risk of other complications including pain, fever, and haematuria, and no significant difference in the likelihood of requiring auxiliary procedures or re-treatment. CONCLUSIONS: There was a reduced risk of steinstrasse in patients undergoing SWL with a JJ stent compared to SWL alone. However, there was no significant difference in the risk of other postoperative complications. Use of a JJ stent had no effect on the efficacy of SWL, with no significant difference in the SFR.

Using machine learning techniques to predict antimicrobial resistance in stone disease patients.

PURPOSE: Artificial intelligence is part of our daily life and machine learning techniques offer possibilities unknown until now in medicine. This study aims to offer an evaluation of the performance of machine learning (ML) techniques, for predicting bacterial resistance in a urology department. METHODS: Data were retrieved from laboratory information system (LIS) concerning 239 patients with urolithiasis hospitalized in the urology department of a tertiary hospital over a 1-year period (2019): age, gender, Gram stain (positive, negative), bacterial species, sample type, antibiotics and antimicrobial susceptibility. In our experiments, we compared several classifiers following a tenfold cross-validation approach on 2 different versions of our dataset; the first contained only information of Gram stain, while the second had knowledge of bacterial species. RESULTS: The best results in the balanced dataset containing Gram stain, achieve a weighted average receiver operator curve (ROC) area of 0.768 and F-measure of 0.708, using a multinomial logistic regression model with a ridge estimator. The corresponding results of the balanced dataset, that contained bacterial species, achieve a weighted average ROC area of 0.874 and F-measure of 0.783, with a bagging classifier. CONCLUSIONS: Artificial intelligence technology can be used for making predictions on antibiotic resistance patterns when knowing Gram staining with an accuracy of 77% and nearly 87% when identifying specific microorganisms. This knowledge can aid urologists prescribing the appropriate antibiotic 24-48 h before test results are known.

Fragility index of urological literature regarding medical expulsive treatment.

INTRODUCTION: The role of medical expulsive treatment (MET) is controversial. Fragility index is an additional metric to assess randomized controlled trials (RCTs) outcome validity and indicates how many patients would be required to convert a trial from being statistically significant, to not significant. The larger is the FI, the better the trial's data. The aim of this study is to assess FI of RCTs regarding MET for ureteral stones. MATERIALS AND METHODS: A systematic literature search was performed. RCTs, reporting stone expulsion as a dichotomous outcome, showing statistical significance were eligible. FI (the number of patients needed to change from a non-event to event group, to lose statistical significance) and Fragility quotient (FI divided by total sample size), were calculated while Pearson's correlation and Mann-Whitney U test were used as appropriate. RESULTS: Thirty-six RCTs were eligible, with median FI = 3.5 and fragility quotient = 0.042, median sample size = 81, median journal impact factor = 1.73 and median reported p value = 0.008. In 33.3% of the studies, number of patients lost during follow-up was larger than FI, while in 13.89% of the studies, FI was 0, indicating use of inappropriate statistical method. Pearson's correlation showed significant positive association between FI and sample size (r = 0.981), number of events (r = 0.982) and impact factor (r = 0.731), while no association was found with p value or publication year. CONCLUSIONS: In this analysis, a calculated FI of 3.5 indicates that findings from RCTs on MET for ureteral stones are fragile and should be interpreted in combination with clinical thinking and expertise.

Outcomes of dissolution therapy and monitoring for stone disease: should we do better?

PURPOSE OF REVIEW: Surgical management is the cornerstone of urolithiasis treatment, but high recurrence rates and associated complications necessitate the existence of medical treatment options, aiming at dissolution of kidney stones and prevention of recurrence. The purpose of this review is to present the most recent knowledge existing in scientific literature, regarding dissolution therapy and ways of monitoring nephrolithiasis patients. RECENT FINDINGS: A number of laboratory studies have been performed testing experimental treatments (tolvaptan, chlorthalidone, atorvastatin, a-lipoic acid, glucosaminoglycans, plant extracts), to reduce kidney stone formation and cellular damage and showed encouraging results. Uric acid stones is the main target of dissolution therapy, but until last years, existing level of evidence was low. A number of prospective and randomized studies, proved the efficacy and safety of oral chemolysis for radiolucent stones and associated prognostic features of success. Tolvaptan and a-Lipoic acid were also tested in patients with cystinuria and resulted in reduction of recurrence. Finally, some new diagnostic markers are suggested as tests for the monitoring of urolithiasis patients, with satisfying accuracy and discriminative ability. SUMMARY: Medical dissolution therapy for nephrolithiasis is an effective option, especially for patients with radiolucent/uric acid stones. In the future, we need clinical trials to confirm the encouraging results of pilot studies testing several agents for patients with cystinuria.

Complications after active stone removal.

PURPOSE OF REVIEW: Active stone removal has been entirely revolutionized in the past decades. Smaller instruments, scope and laser technology advancements and novel lithotripter modalities have entirely changed the way urological surgeons treat stones. Nevertheless novel technologies may lead to different and difficult to manage complications. Accurate knowledge of indications, limitations and technical details of these novel modalities can significantly decrease complication rates. The purpose of this review is to provide the most recently acquired knowledge to decrease patient's morbidity after active stone removal. RECENT FINDINGS: Complications of active stone removal are well known for many years, nevertheless novel technologies in stone management can substantially differentiate their rates. Minimal invasive techniques are becoming even more minimal which reflects on the complications. SUMMARY: Mastering the novel techniques in active stone removal and knowing their inherent limitations, in association with the recognition of predisposing factors and preventing measures have led to a highly acceptable low complication rate. Further refinements and technical improvement will reduce even more the complication incidence in the future.

A prospective comparative analysis of robot-assisted vs open simple prostatectomy for benign prostatic hyperplasia.

OBJECTIVE: To report the first prospective comparative analysis of robot-assisted (RASP) vs open simple prostatectomy (OSP) for large prostate glands. MATERIALS AND METHODS: We prospectively analysed 41 patients who underwent surgery for benign prostatic hyperplasia between 2014 and 2017 at one of two university institutions. Patients were grouped according to the procedure (OSP or RASP) and matched in terms of age, prostate volume, body mass index and prostate-specific antigen level. The two groups were followed prospectively for 3 months, and their postoperative and functional outcomes were compared. RESULTS: Six patients (40%) in the OSP and seven patients (27%) in the RASP arm of the study had preoperative urethral catheters as a result of relapsed urinary retention. The amount of blood loss during surgery was significantly lower in the RASP arm (539  vs 274 mL), but the operating time was significantly longer (134 vs 88 min). One patient in the RASP group experienced a Clavien-Dindo grade II complication, whereas in the OSP group, four patients experienced serious complications (27%); one patient had a bladder rupture (Grade III), one patient developed deep venous thrombosis (Grade II), and two patients required blood transfusions (one unit each; Grade II). Two patients (one from each group) experienced urinary retention after catheter removal that required a urethral catheter replacement. In the follow-up period, there were significant and similar improvements in International Prostate Symptom Scores, uroflowmetry results and post-void residual urine volume in both groups. CONCLUSION: The results showed that RASP provided similar functional outcomes to those of OSP, whilst maintaining a good (or even better) safety profile. Our results suggest that RASP is a viable, efficient and potentially superior alternative to the open procedure.

Robot-Assisted Bladder Diverticulectomy with Concurrent Management of Bladder Outlet Obstruction.

INTRODUCTION: Robot-assisted bladder diverticulectomy (RABD) through a technique for easier identification of diverticulum along with concomitant management of bladder outlet obstruction (BOO) utilizing a combination of transurethral prostatectomy (TUR-P) and photoselective vaporization of prostate (PVP) is presented. MATERIALS AND METHODS: Between 2008 and 2015, 9 patients underwent RABD with concurrent treatment of BOO. Diverticula were identified by a technique of catheterizing the diverticulum and the bladder simultaneously and individually. RESULTS: Mean patient age was 62 ± 9.8 and prostate volume was 70 ± 26 ml. Mean time for endourological procedure was 77 ± 35, mean console and total operative times were 108 ± 38 and 186 ± 56 min, respectively. Mean estimated blood loss was 71 ± 37 ml. All diverticula were excised and BOO treated successfully. Bladder irrigation was not necessary in any patient. Mean hospitalization and catheter removal time was 5 ± 3 and 8 ± 3 days, respectively. No complications were observed. CONCLUSIONS: BOO is the main cause of acquired bladder diverticula and is largely due to benign prostatic hyperplasia. Concomitant performance of TUR-P and PVP along with RABD is feasible and safe. Individual catheterization of the diverticulum and bladder facilitates the identification of diverticulum even in the presence of multiple diverticula.

The use of indocyanine green in partial nephrectomy: a systematic review.

Introduction: The aim of this review was to assess the outcomes of partial nephrectomy using indocyanine green (ICG) regarding ischemia time, positive surgical margins (PSM), estimated blood loss (EBL) and estimated GFR reduction while also suggesting the optimal dosage scheme. Material and methods: A systematic review was performed using Medline (PubMed), ClinicalTrials.gov, and Cochrane Library (CENTRAL) databases, in concordance with the PRISMA statement. Studies in English regarding the use of indocyanine green in partial nephrectomy were reviewed. Reviews and meta-analyses, editorials, perspectives, and letters to the editors were excluded. Results: Individual ICG dose was 5 mg in most of the studies. The mean warm ischemia time (WIT) on each study ranged from 11.6 minutes to 27.2 minutes. The reported eGFR reduction ranged from 0% to 15.47%. Lowest mean EBL rate was 48.2 ml and the highest was 347 ml. Positive surgical margin rates were between 0.3% to 11%. Conclusions: Indocyanine green seems to be a useful tool in partial nephrectomy as it can assist surgeons in identifying tumor and its related vasculature. Thereby, warm ischemia time can be reduced and, in some cases, selective ischemia can be implemented leading to better renal functional preservation.

Treatment of urge incontinence in postmenopausal women: A systematic review.

BACKGROUND: Urinary incontinence and other urinary symptoms tend to be frequent at menopause because of hormonal modifications and aging. Urinary symptoms are associated with the genitourinary syndrome of menopause which is characterized by physical changes of the vulva, vagina and lower urinary tract. The treatment strategies for postmenopausal urinary incontinence are various and may include estrogens, anticholinergics, and pelvic floor muscle training. A comparison of these treatments is difficult due to the heterogeneity of adopted protocols. We systematically reviewed the evidence from randomized controlled trials (RCTs) focusing on treatment of postmenopausal women with urge incontinence. METHODS: We conducted a systematic review and meta-analysis by searching PubMed and EMBASE databases for randomized controlled trials (RCTs) reporting results of treatments for postmenopausal urinary urge incontinence. Odds ratios for improvement of urinary incontinence were calculated using random effect Mantel-Haenszel statistics. RESULTS: Out of 248 records retrieved, 35 eligible RCTs were assessed for risk of bias and included in the meta-analysis. Compared with placebo, systemic estrogens were associated with decreased odds of improving urinary incontinence in postmenopausal women (OR = 0.74, 95% CI: 0.61-0.91, 7 series, 17132 participants, Z = 2.89, P = 0.004, I2 = 72%). In most studies, no significant improvement in urinary symptoms was observed in patients treated with local estrogens, although they showed to be helpful in improving vaginal symptoms. Vitamin D, phytoestrogens and estrogen modulators were not effective in improving symptoms of incontinence and other symptoms of genitourinary menopause syndrome or yielded contradictory results. A randomized controlled trial demonstrated that oxybutynin was significantly better than placebo at improving postmenopausal urgency and urge incontinence. The combination of anticholinergics with local estrogens has not been shown to be more effective than anticholinergics alone in improving urinary incontinence symptoms in postmenopausal women. Physical therapy showed an overall positive outcome on postmenopausal urinary incontinence symptoms, although such evidence should be further validated in the frame of quality RCTs. CONCLUSIONS: The evidence for effective treatment of postmenopausal urinary incontinence is still lacking. Welldesigned large studies having subjective and objective improvement primary endpoints in postmenopausal urinary incontinence are needed. At present, a combination of different treatments tailored to the characteristics of the individual patient can be suggested.

Risk of urogenital infections in non-diabetic patients treated with sodium glucose transporter 2 (SGLT2) inhibitors. Systematic review and meta-analysis.

Although SGLT2 inhibitors have been initially employed in the treatment of type 2 diabetes, their clinical use was later extended to the treatment of other conditions such as heart failure, chronic kidney disease and obesity. In patients with type 2 diabetes, the administration of SGLT2 inhibitors has been associated with an increased incidence of urogenital infections, which may be linked to high glucose levels in the urine. The rate of urogenital side effects may be different in non-diabetic patients. The aim of this study was to review the risk of urogenital infections in non-diabetic patients taking SGLT2 inhibitors. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis by searching PubMed and EMBASE for randomized controlled trials (RCTs) reporting urogenital adverse effects in non-diabetic patients treated with SGLT2 inhibitors. Odds ratios for urogenital infections were calculated using random effect Mantel-Haenszel statistics. RESULTS: Out of 387 citations retrieved, 12 eligible RCTs were assessed for risk of bias and included in the meta-analysis. Compared to placebo, SGLT2 inhibitors were associated with increased odds of genital infections (OR 3.01, 95% CI: 1.93- 4.68, 9 series, 7326 participants, Z = 5.74, p < 0.0001, I2 = 0%) as well as urinary tract infections (OR 1.33, 95% CI: 1.13-1.57, 9 series, 7326 participants, Z = 4.05, p < 0.0001, I2 = 0%). When four trials investigating the effects of SGLT2 inhibitors in populations including both diabetic and non-diabetic patients were considered, administration of SGLT2 inhibitors in diabetic patients was associated with significantly higher odds of genital infections but not urinary tract infections compared to patients without type 2 diabetes. In patients taking placebo, the odds for urinary tract infections were significantly increased in diabetic patients compared to non-diabetic patients. CONCLUSIONS: The risk of genital infections is increased also in non-diabetic patients taking SGLT2 inhibitors although at a lesser extent that in diabetics. A careful assessment of the local anatomical conditions and of the history of previous urogenital infections is desirable to select those patients who need more intense follow-up, possibly combined with prophylactic measures of infections during treatment with SGLT2 inhibitors.

Optimal Delivery of Follow-Up Care for the Prevention of Stone Recurrence in Urolithiasis Patients: Improving Outcomes.

Urolithiasis is a common clinical condition with frequent recurrences. Advances in knowledge of pathophysiological mechanisms permit the categorization of patients to low and high risk for recurrence, with specific metabolic abnormalities diagnosed in the second category. Follow-up is essential for patients with urolithiasis and consists of both imaging and metabolic follow-up with urine studies. No formal guidelines or solid evidence currently exists regarding frequency and type of follow-up studies to be performed in each category. This review aims to summarize existing evidence regarding follow-up, in order to guide clinicians on how and when to follow-up urolithiasis patients according to existing clinical scenario.

Shockwave Lithotripsy Complications According to Modified Clavien-Dindo Grading System. A Systematic Review and Meta-regression Analysis in a Sample of 115 Randomized Controlled Trials.

CONTEXT: Shockwave lithotripsy (SWL) shows clear associated benefits for urolithiasis patients. OBJECTIVE: To identify and classify SWL complications according to modified Clavien-Dindo grading system while assessing the effect of different patient characteristics, stone parameters, types of lithotripters, and lithotripsy techniques. EVIDENCE ACQUISITION: Literature was reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. EVIDENCE SYNTHESIS: We analyzed the results of 115 randomized trials including 17827 patients, of whom 16.06%, 2.07%, 2.23%, 1.32%, 0.85%, 0.16%, and 0% suffered from Clavien I, II, III, IIIa, IIIb, IV, and V complications, respectively. In total, 18.43% of patients suffered from Clavien I-II and 2.48% from Clavien III-IV complications. In studies with >100 treated patients, Clavien I, III, and IV complication rates and need for auxiliary procedure rates were lower than in studies with smaller sample size. Electrohydraulic lithotripters led to a higher rate of Clavien IIIb and IV complications than electromagnetic lithotripters. Clavien I-II complications were increased by 14.3% in patients with multiple and complicated stones. Hematuria was increased by 8.29% in patients who underwent intravenous urography preoperatively and had longer duration of SWL. Pain occurrence was increased by 14.79% in patients with more than one stone at the time of SWL and by 3.21% in those who were managed with a piezoelectric lithotripter. CONCLUSIONS: SWL should not be considered an uneventful procedure, as in 2.5% of cases an intervention or Clavien III-V complication will be observed. Low-volume centers, treatment of multiple or complex stones, a long-lasting SWL session, and electrohydraulic lithotripters are associated with higher rates of complications. PATIENT SUMMARY: We analyze the occurrence of shockwave lithotripsy (SWL) complications in 17000 patients. In centers with larger caseloads, complications were less common. The type of lithotripter is associated with complications. An increased number of treated stones, complex stones, and increased SWL duration were associated with a higher incidence of pain and hematuria.

Effect of alpha-adrenoceptor antagonists on sexual function. A systematic review and meta-analysis.

BACKGROUND: Alpha-adrenoreceptor antagonists or alpha-blockers are used in the treatment of hypertension, in the therapy of benign prostatic hyperplasia and in medical expulsive treatment of ureteral stones. These agents may affect the sexual function, with differences between drugs within the same class, depending on their selectivity for receptor subtypes. The aim of this review was to analyze the effects of alpha-blockers on sexual function. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis by searching PubMed, EMBASE and other databases for randomized controlled trials (RCTs) reporting sexual adverse effects in patients treated with alpha-blockers. Odds ratios for sexual dysfunction were calculated using random effects Mantel-Haenszel statistics. RESULTS: Out of 608 records retrieved, 75 eligible RCTs were included in the meta-analysis. Compared with placebo, alphablockers were associated with increased odds of ejaculatory disorders both in patients with lower urinary tract symptoms (LUTS) associated to benign prostatic hyperplasia (BPH) (OR: 7.53, 95% CI: 3.77-15.02, Z = 5.73, p < 0.00001, I2 = 55%) and in patients with ureteral stones (OR: 2.88, 95% CI: 1.50-5.44, Z = 3.19, p < 0.001, I2 = 31%). Uroselective alpha-blockers showed higher odds of ejaculatory disorders. Conversely, nonselective alpha-blockers were not associated with higher odds of ejaculatory dysfunction. Silodosin was associated with increased odds of ejaculatory dysfunction compared with tamsulosin (OR: 3.52, 95% CI: 2.18-5.68, 15 series, 1512 participants, Z = 5.15, p < 0.00001, I2 = 0%). Naftopidil and alfuzosin showed lower odds of ejaculatory dysfunction compared to uroselective alpha-blockers.No statistically significant differences in the odds of erectile dysfunction were observed when alpha-blockers were compared to placebo.

Infectious complications of endourological treatment of kidney stones: A meta-analysis of randomized clinical trials.

OBJECTIVE: Endourological treatment is associated with a risk of postoperative febrile urinary tract infections and sepsis. The aim of this study was to review the reported rate of infectious complications in relation to the type and modality of the endourologic procedure. METHODS: This systematic review was conducted in accordance with the PRISMA guidelines. Two electronic databases (PubMed and EMBASE) were searched. Out of 243 articles retrieved we included 49 studies after full-text evaluation. RESULTS: Random-effects meta-analysis demonstrated that retrograde intrarenal surgery (RIRS) and percutaneous nephrolithotomy (PCNL) were associated with not significantly different odds of getting fever (OR = 1.54, 95% CI: 0.99 to 2.39; p = 0.06) or sepsis (OR = 1.52, 95% CI: 0.37 to 6.20, p = 0.56). The odds of getting fever were not significantly different for mini PCNL compared to standard PCNL (OR = 1.11, 95% CI: 0.85 to 1.44; p = 0.45) and for tubeless PCNL compared to standard PCNL (OR = 1.34 95% CI: 0.61 to 2.91, p = 0.47). However, the odds for fever after PCNL with suctioning sheath were lower than the corresponding odds for standard PCNL (OR = 0.37, 95% CI: 0.20 to 0.70, p = 0.002). The odds of getting fever after PCNL with perioperative prophylaxis were not different from the corresponding odds after PCNL with perioperative prophylaxis plus a short oral antibiotic course (before or after the procedure) (OR = 1.31, 95% CI: 0.71 to 2.39, p = 0.38). CONCLUSIONS: The type of endourological procedure does not appear to be decisive in the onset of infectious complications, although the prevention of high intrarenal pressure during the procedure could be crucial in defining the risk of infectious complications.   on behalf of U-merge Ltd. (Urology for emerging countries), London-Athens-Dubai.

One step nucleic acid amplification (OSNA) for detection of lymph node metastasis during robotic radical prostatectomy for prostate cancer: A pilot study.

INTRODUCTION: The OSNA technique is based on reverse transcription loop-mediated DNA amplification for the detection of cytokeratin 19 (CK19) messen-ger RNA (mRNA). The purpose of our paper, which represents the first study in the literature, is to test the accuracy of this method in the detection of lymph node metastases in patients undergoing robotic radical prostatectomy with lymph node dis-section. METHODS: Our cohort consisted of patients that have undergone robotic radical prostatectomy with extended lymph node dissec-tion. Lymph nodes were evaluated with imprint technique and then with frozen section examination. The remaining tissue was evaluated by OSNA method. Lymph nodes were defined as 'neg-ative' or 'positive' according to mRNA copy number. RESULTS: 7 patients and 25 lymph nodes were included in our cohort. Two patients were found negative with all pathology methods. In one patient the standard stains revealed a suspi-cious outcome but it was positive for micrometastasis with OSNA. In another patient the outcome was positive for standard stains and negative for OSNA. Finally, 2 patients were found positive for OSNA and negative for imprint methods. CONCLUSIONS: One Step Nucleic Acid Amplification (OSNA) method using CK19 seems to fail in detection of lymph node metastases in prostate cancer patients undergoing radical prostatectomy and lymph node dissection.

Risk of urinary stone formation associated to proton pump inhibitors: A systematic review and metanalysis.

OBJECTIVE: Proton pump inhibitors are widely used as treatment of acid-related disorders. They are considered safe although their long-term use has been associated with some adverse effects including an increased propensity for urinary calculi formation. The aim of this study was to systematically review available data from studies evaluating the association of PPIs and nephrolithiasis. MATERIALS AND METHODS: We searched two electronic databases (PubMed and EMBASE) for cohort studies or case-control studies evaluating the relationship between treatment with proton pump inhibitors and the risk of stone formation published up to 31 October 2022. The overall association of PPIs and urinary calculi was analyzed using a random effects model (RevMan5). The quality of the included studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. RESULTS: A total of 550 studies were retrieved; 7 were selected by title and abstract screening; after removal of duplicates, 4 records were evaluated by full-text examination. An additional study was retrieved by handsearching the references included in screened studies. In the unadjusted analysis, the odds of urinary calculi were greater in subjects taking PPIs compared to controls (unadjusted OR = 2.10, 95% CI 1.74-2.52, p < 0.00001). The pooled odds ratio of two case-control studies confirmed that use of PPIs increased the odds of urinary calculi compared with non-use (OR 2.44, 95% CI 2.29 to 2.61). Pooled analysis of three cohort studies evaluating incident nephrolithiasis showed an overall hazard ratio estimate of 1.34 (95% CI = 1.28-1.40). One study found lower urinary citrate and urinary magnesium levels in subjects exposed to PPIs. The Newcastle-Ottawa Quality Assessment Scale scores ranged between 6 and 8. CONCLUSIONS: PPIs showed an association with urinary calculi in patients included in the studies included in this review. If these data will be confirmed in adequately powered randomized trials, clinicians may consider limiting the long-term use of PPIs, to avoid unnecessary prolongation of treatment. Urinary magnesium and citrate should be evaluated in renal stone forming patients taking PPIs to supplement their intake when requested.

Efficacy of overactive neurogenic bladder treatment: A systematic review of randomized controlled trials.

BACKGROUND: Overactive bladder (OAB) symptoms of frequency, urgency and urge incontinence are frequently associated with known neurological diseases like multiple sclerosis (MS), spinal cord injury (SCI), Parkinson's disease (PD), stroke. OBJECTIVE: The aim of our study was to review the efficacy of pharmacological and non-pharmacological treatments for neurogenic overactive bladder. MATERIALS AND METHODS: We searched two electronic databases (PubMed and EMBASE) for randomized controlled trials focusing on pharmacological and non-pharmacological medical treatments for overactive bladder symptoms associated with neurological diseases published up to 30 April 2022. RESULTS: A total of 157 articles were retrieved; 94 were selected by title and abstract screening; after removal of 17 duplicates, 77 records were evaluated by full-text examination. Sixty-two studies were finally selected. The articles selected for review focused on the following interventions: anticholinergics (n = 9), mirabegron (n = 5), comparison of different drugs (n = 3), cannabinoids (n = 2), intravesical instillations (n = 3), botulinum toxin (n = 16), transcutaneous tibial nerve stimulation (TTNS) (n = 6), acupuncture (n = 2), transcutaneous electrical nerve stimulation TENS (n = 4), pelvic floor muscle training (PFMT) (n = 10), others (n = 2). Anticholinergics were more effective than placebo in decreasing the number of daily voids in patients with PD (mean difference [MD]- 1.16, 95 % CI - 1.80 to - 0.52, 2 trials, 86 patients, p < 0.004), but no significant difference from baseline was found for incontinence episodes and nocturia. Mirabegron was more effective than placebo in increasing the cystometric capacity in patients with MS (mean difference [MD] 89.89 mL, 95 % CI 29.76 to 150.01, 2 trials, 98 patients, p < 0.003) but no significant difference was observed for symptom scores and bladder diary parameters. TTNS was more effective than its sham-control in decreasing the number of nocturia episodes (MD -1.40, 95 % CI -2.39 to -0.42, 2 trials, 53 patients, p < 0.005) but no significant changes of OAB symptom scores were reported. PFMT was more effective than conservative advice in decreasing the ICIQ symptom score (MD, -1.12, 95 % CI -2.13 to -0.11, 2 trials, 91 patients, p = 0.03), although the number of incontinence episodes was not significantly different between groups. CONCLUSIONS: The results of the meta-analysis demonstrate a moderate efficacy of all considered treatments without proving the superiority of one therapy over the others. Combination treatment using different pharmacological and non-pharmacological therapies could achieve the best clinical efficacy due to the favorable combination of the different mechanisms of action. This could be associated with fewer side effects due to drug dosage reduction. These data are only provisional and should be considered with caution, due to the few studies included in metaanalysis and to the small number of patients.