Effect of bladder outlet procedures on urodynamic assessments in men with an acontractile or underactive detrusor: A systematic review and meta-analysis.

OBJECTIVE: To review the effect of bladder outlet procedures on urodynamic outcomes and symptom scores in males with detrusor underactivity (DU) or acontractile detrusors (AD). MATERIALS AND METHODS: We performed a systematic review and meta-analysis of research publications derived from PubMed, Embase, Web of Science, and Ovid Medline to identify clinical studies of adult men with non-neurogenic DU or AD who underwent any bladder outlet procedure. Outcomes comprised the detrusor pressure at maximum flow (Pdet Qmax ), maximum flow rate (Qmax ), international prostate symptom score (IPSS), and quality of life (QoL). This study is registered under PROSPERO CRD42020215832. RESULTS: We included 13 studies of bladder outlet procedures, of which 6 reported decreased and 7 reported improved Pdet Qmax after the procedure. Meta-analysis revealed an increase in the pooled mean Pdet Qmax of 5.99 cmH2 0 after surgery (95% CI: 0.59-11.40; p = 0.03; I2 95%). Notably, the Pdet Qmax improved in all subgroups with a preoperative bladder contractility index (BCI) <50 and decreased in all subgroups with a BCI ≥50. All studies reported an improved Qmax after surgery, with a pooled mean difference of 5.87 mL/s (95% CI: 4.25-7.49; I2 93%). Only three studies reported QoL, but pooling suggested significant improvements after surgery (mean, -2.41 points; 95% CI: -2.81 to -2.01; p = 0.007). All seven studies reporting IPSS demonstrated improvement (mean, -12.82; 95% CI: -14.76 to -10.88; p < 0.001). CONCLUSIONS: This review shows that Pdet Qmax and Qmax increases after surgical bladder outlet procedures in men with DU and AD. Bladder outlet procedures should be discussed as part of the shared decision-making process for this group. The evidence was of low to very low certainty.

Maternal risk factors for posterior urethral valves.

Introduction: Posterior urethral valves (PUV) is a congenital disorder causing an obstruction of the lower urinary tract that affects approximately 1 in 4,000 male live births. PUV is considered a multifactorial disorder, meaning that both genetic and environmental factors are involved in its development. We investigated maternal risk factors for PUV. Methods: We included 407 PUV patients and 814 controls matched on year of birth from the AGORA data- and biobank and three participating hospitals. Information on potential risk factors (family history of congenital anomalies of the kidney and urinary tract (CAKUT), season of conception, gravidity, subfertility, and conception using assisted reproductive techniques (ART), plus maternal age, body mass index, diabetes, hypertension, smoking, and use of alcohol and folic acid) was derived from maternal questionnaires. After multiple imputation, adjusted odds ratios (aORs) were estimated using conditional logistic regression corrected for minimally sufficient sets of confounders determined using directed acyclic graphs. Results: A positive family history and low maternal age (<25 years) were associated with PUV development [aORs: 3.3 and 1.7 with 95% confidence intervals (95% CI) 1.4-7.7 and 1.0-2.8, respectively], whereas higher maternal age (>35 years) was associated with a lower risk (aOR: 0.7 95% CI: 0.4-1.0). Maternal preexisting hypertension seemed to increase PUV risk (aOR: 2.1 95% CI: 0.9-5.1), while gestational hypertension seemed to decrease this risk (aOR: 0.6 95% CI: 0.3-1.0). Concerning use of ART, the aORs for the different techniques were all above one, but with very wide 95% CIs including one. None of the other factors studied were associated with PUV development. Conclusion: Our study showed that family history of CAKUT, low maternal age, and potentially preexisting hypertension were associated with PUV development, whereas higher maternal age and gestational hypertension seemed to be associated with a lower risk. Maternal age and hypertension as well as the possible role of ART in the development of PUV require further research.

Cost Effectiveness of Rectal Culture-based Antibiotic Prophylaxis in Transrectal Prostate Biopsy: The Results from a Randomized, Nonblinded, Multicenter Trial.

Background: Culture-based antibiotic prophylaxis is a plausible strategy to reduce infections after transrectal prostate biopsy (PB) related to fluoroquinolone-resistant pathogens. Objective: To assess the cost effectiveness of rectal culture-based prophylaxis compared with empirical ciprofloxacin prophylaxis. Design setting and participants: The study was performed alongside a trial in 11 Dutch hospitals investigating the effectiveness of culture-based prophylaxis in transrectal PB between April 2018 and July 2021 (trial registration number: NCT03228108). Intervention: Patients were 1:1 randomized for empirical ciprofloxacin prophylaxis (oral) or culture-based prophylaxis. Costs for both prophylactic strategies were determined for two scenarios: (1) all infectious complications within 7 d after biopsy and (2) culture-proven Gram-negative infections within 30 d after biopsy. Outcome measurements and statistical analysis: Differences in costs and effects (quality-adjusted life-years [QALYs]) were analyzed from a healthcare and societal perspective (including productivity losses, and travel and parking costs) using a bootstrap procedure presenting uncertainty surrounding the incremental cost-effectiveness ratio in a cost-effectiveness plane and acceptability curve. Results and limitations: For the 7-d follow-up period, culture-based prophylaxis (n = 636) was €51.57 (95% confidence interval [CI] 6.52-96.63) more expensive from a healthcare perspective and €16.95 (95% CI -54.29 to 88.18) from a societal perspective than empirical ciprofloxacin prophylaxis (n = 652). Ciprofloxacin-resistant bacteria were detected in 15.4%. Extrapolating our data, from a healthcare perspective, 40% ciprofloxacin resistance would lead to equal cost for both strategies. Results were similar for the 30-d follow-up period. No significant differences in QALYs were observed. Conclusions: Our results should be interpreted in the context of local ciprofloxacin resistance rates. In our setting, from a healthcare perspective, culture-based prophylaxis was significantly more expensive than empirical ciprofloxacin prophylaxis. From a societal perspective, culture-based prophylaxis was somewhat more cost effective against the threshold value customary for the Netherlands (€80.000). Patient summary: Culture-based prophylaxis in transrectal prostate biopsy was not associated with reduced costs compared with empirical ciprofloxacin prophylaxis.

Managing children with daytime urinary incontinence: a survey of Dutch general practitioners.

BACKGROUND: In the Netherlands, parents of children with daytime urinary incontinence (UI) first consult general practitioners (GPs). However, GPs need more specific guidelines for daytime UI management, resulting in care and referral decisions being made without clear guidance. OBJECTIVES: We aimed to identify Dutch GP considerations when treating and referring a child with daytime UI. METHODS: We invited GPs who referred at least one child aged 4-18 years with daytime UI to secondary care. They were asked to complete a questionnaire about the referred child and the management of daytime UI in general. RESULTS: Of 244 distributed questionnaires, 118 (48.4%) were returned by 94 GPs. Most reported taking a history and performing basic diagnostic tests like urine tests (61.0%) and physical examinations (49.2%) before referral. Treatment mostly involved lifestyle advice, with only 17.8% starting medication. Referrals were usually at the explicit wish of the child/parent (44.9%) or because of symptom persistence despite treatment (39.0%). GPs usually referred children to a paediatrician (n = 99, 83.9%), only referring to a urologist in specific situations. Almost half (41.4%) of the GPs did not feel competent to treat children with daytime UI and more than half (55.7%) wanted a clinical practice guideline. In the discussion, we explore the generalisability of our findings to other countries. CONCLUSION: GPs usually refer children with daytime UI to a paediatrician after a basic diagnostic assessment, usually without offering treatment. Parental or child demand is the primary stimulus for referral.

Rectal Culture-Based Versus Empirical Antibiotic Prophylaxis to Prevent Infectious Complications in Men Undergoing Transrectal Prostate Biopsy: A Randomized, Nonblinded Multicenter Trial.

BACKGROUND: An increase in infections after transrectal prostate biopsy (PB), related to an increasing number of patients with ciprofloxacin-resistant rectal flora, necessitates the exploration of alternatives for the traditionally used empirical prophylaxis of ciprofloxacin. We compared infectious complication rates after transrectal PB using empirical ciprofloxacin prophylaxis versus culture-based prophylaxis. METHODS: In this nonblinded, randomized trial, between 4 April 2018 and 30 July 2021, we enrolled 1538 patients from 11 Dutch hospitals undergoing transrectal PB. After rectal swab collection, patients were randomized 1:1 to receive empirical prophylaxis with oral ciprofloxacin (control group [CG]) or culture-based prophylaxis (intervention group [IG]). Primary outcome was any infectious complication within 7 days after biopsy. Secondary outcomes were infectious complications within 30 days, and bacteremia and bacteriuria within 7 and 30 days postbiopsy. For primary outcome analysis, the χ2 test stratified for hospitals was used. Trial registration number: NCT03228108. RESULTS: Data from 1288 patients (83.7%) were available for analysis (CG, 652; IG, 636). Infection rates within 7 days postbiopsy were 4.3% (n = 28) (CG) and 2.5% (n = 16) (IG) (P value = .08; reduction: -1.8%; 95% confidence interval, -.004 to .040). Ciprofloxacin-resistant bacteria were detected in 15.2% (n = 1288). In the CG, the presence of ciprofloxacin-resistant rectal flora resulted in a 6.2-fold higher risk of early postbiopsy infection. CONCLUSIONS: Our study supports the use of culture-based prophylaxis to reduce infectious complications after transrectal PB. Despite adequate prophylaxis, postbiopsy infections can still occur. Therefore, culture-based prophylaxis must be weighed against other strategies that could reduce postbiopsy infections. Clinical Trials Registration. NCT03228108.

Uncovering risk factors for kidney injury in children with a solitary functioning kidney.

Children with a solitary functioning kidney (SFK) have an increased risk of kidney injury. The exact risk of and risk factors for kidney injury remain unknown, which impedes personalized care. Here, we recruited a nationwide multicenter cohort of 944 patients with SFK to get more insight into this by consenting patients born in 1993-2020 and diagnosed with congenital or acquired SFK before adulthood. The median follow-up was 12.8 years and four indications of kidney injury were studied: urine protein-creatinine ratios, blood pressure, estimated glomerular filtration rate and use of anti-hypertensive/proteinuric medication. For each indicator except medication use, separate cut-off values for any injury and severe injury were used. Survival analyses indicated that at 18 years of age, any or severe kidney injury were present in 75% and 39% of patients with congenital SFK, respectively. Risk factors for kidney injury included kidney agenesis as cause of the SFK, anomalies in the SFK, and high body mass index at last follow-up. Kidney agenesis and being overweight were specifically associated with proteinuria and high blood pressure, whereas anomalies in the SFK were associated with reduced estimated glomerular filtration rates. The high prevalence of kidney injury in patients with SFK emphasizes the need for long-term follow-up, in which lifestyle is an important topic to address. More research into the etiological role of risk factors will help to translate our findings into individualized care strategies. Thus, our study shows that a significant proportion of children with SFK will develop kidney injury over time.

Genome-wide association study in patients with posterior urethral valves.

Congenital lower urinary tract obstructions (LUTO) are most often caused by posterior urethral valves (PUV), a male limited anatomical obstruction of the urethra affecting 1 in 4,000 male live births. Little is known about the genetic background of PUV. Here, we report the largest genome-wide association study (GWAS) for PUV in 4 cohorts of patients and controls. The final meta-analysis included 756 patients and 4,823 ethnicity matched controls and comprised 5,754,208 variants that were genotyped or imputed and passed quality control in all 4 cohorts. No genome-wide significant locus was identified, but 33 variants showed suggestive significance (P < 1 × 10-5). When considering only loci with multiple variants residing within < 10 kB of each other showing suggestive significance and with the same effect direction in all 4 cohorts, 3 loci comprising a total of 9 variants remained. These loci resided on chromosomes 13, 16, and 20. The present GWAS and meta-analysis is the largest genetic study on PUV performed to date. The fact that no genome-wide significant locus was identified, can be explained by lack of power or may indicate that common variants do not play a major role in the etiology of PUV. Nevertheless, future studies are warranted to replicate and validate the 3 loci that yielded suggestive associations.

Magnetic Resonance Imaging-targeted Prostate Biopsy Compared with Systematic Prostate Biopsy in Biopsy-naïve Patients with Suspected Prostate Cancer.

Background: It remains uncertain whether transrectal ultrasound (TRUS)-guided systematic biopsies can be omitted and rely solely on multiparametric magnetic resonance imaging-targeted biopsies (MRI-TBx) in biopsy-naïve men suspected of prostate cancer (PCa). Objective: To compare PCa detection in biopsy-naïve men between systematic biopsy and MRI-TBx. Design setting and participants: A prospective cohort study was conducted in a Dutch teaching hospital. Consecutive patients with suspected PCa, no history of biopsy, and no clinical suspicion of metastasis underwent both TRUS-guided systematic biopsies and MRI-TBx by multiparametric magnetic resonance imaging (mpMRI)-ultrasound fusion, including sham biopsies in case of negative mpMRI. Outcome measurements and statistical analysis: Clinically significant PCa (csPCa), defined as group ≥2 on the International Society of Urological Pathology grading, was detected. Results and limitations: The overall prevalence of csPCa, irrespective of biopsy technique, was 37.4% (132/353) in our population. MRI-TBx were performed in 263/353 (74.5%) patients with suspicious mpMRI (Prostate Imaging Reporting and Data System [PI-RADS] ≥3). The detection rates for csPCa were 39.5% for MRI-TBx and 42.9% for systematic biopsies. The added values, defined as the additional percentages of patients with csPCa detected by adding one biopsy technique, were 8.7% for the systematic biopsies and 5.3% for MRI-TBx. In patients with nonsuspicious mpMRI, five cases (6%) of csPCa were found by systematic biopsies. Conclusions: This study in biopsy-naïve patients suspected for PCa showed that systematic biopsies have added value to MRI-TBx alone in patients with mpMRI PI-RADS >2. Patient summary: We studied magnetic resonance imaging (MRI)-guided prostate biopsy for diagnosing prostate cancer and compared it with the standard method of prostate biopsy. Standard systematic biopsies cannot be omitted in patients with suspicious MRI, as they add to the detection of significant prostate cancer.

Quality appraisal of clinical guidelines for recurrent urinary tract infections using AGREE II: a systematic review.

INTRODUCTION AND HYPOTHESIS: Recommendations for preventing and diagnosing recurrent urinary tract infection (UTI) tend to vary between clinical practice guidelines (CPGs) because of low-quality scientific evidence, potentially leading to practice variation and suboptimal care. We assessed the quality of existing CPGs for recurrent UTI. METHODS: A systematic search was performed from January 2000 to June 2021 in PubMed and EMBASE for CPGs on recurrent UTI prevention or hospital diagnostics in Dutch, English, and Spanish. Each CPG was assessed by four appraisers in a multidisciplinary review team, using the Appraisal of Guidelines, Research, and Evaluation II (AGREE II) instrument. RESULTS: We identified and assessed eight CPGs published between 2013 and 2021. The scope and purpose (mean and standard deviation: 67.3 ± 21.8) and clarity of presentation (74.8 ± 17.6) domains scored highly. However, issues with methods, patient participation, conflict of interests, and facilitators and barriers were common and resulted in lower scores for the rigour of development (56.9 ± 25.9), applicability (19.6 ± 23.4), stakeholder involvement (50.4 ± 24.6), and editorial independence (62.1 ± 23.1) domains. Overall, two CPGs were recommended, three were recommended with modifications, and three were not recommended. CONCLUSIONS: Significant room for improvement exists in the quality of CPGs for recurrent UTI, with most displaying serious limitations in the stakeholder involvement, rigour of development, and applicability domains. These aspects must be improved to decrease diagnostic and therapeutic uncertainty. Developers could benefit from using checklists and following guidelines when developing de novo CPGs.

Comparison of the diagnostic yield of routine versus indicated flowmetry, ultrasound and cystoscopy in women with recurrent urinary tract infections.

INTRODUCTION AND HYPOTHESIS: To quantify and compare the outcomes of routine vs. urologist-requested diagnostic testing for recurrent urinary tract infections (rUTI). METHODS: A retrospective cohort study of patients with rUTI referred to a large non-academic teaching hospital between 2016 and 2018 (Hospital A) and a university hospital between 2014 and 2016 (Hospital B). Electronic medical records were reviewed for baseline and diagnostic data. Women underwent the following assessments routinely: urinalysis, voiding diary, flowmetry in Hospital A and urinalysis, voiding diary, flowmetry, ultrasound, abdominal x-ray and cystoscopy in Hospital B. All other diagnostics were performed by indication in each hospital. RESULTS: We included 295 women from Hospital A and 298 from Hospital B, among whom the mean age (57.6 years) and mean UTI frequency (5.6/year) were comparable, though more were postmenopausal in Hospital A. We identified abnormalities by flowmetry or post-void residual volumes in 134 patients (Hospital A: 79; Hospital B: 55), cystoscopy in 14 patients (Hospital A: 6; Hospital B: 8) and ultrasound in 42 patients (Hospital A: 16; Hospital B: 26), but these differences were not significant. Diagnostics altered treatment in 117 patients (e.g., pelvic floor muscle training, referral to another specialist, surgical intervention), mostly due to flowmetry and post-void residual volume measurement. The retrospective design and absence of follow-up data limit these results. CONCLUSIONS: The routine use of cystoscopy and ultrasound in female patients with rUTIs should not be recommended as they yield few abnormalities and lead to additional costs.

Compensatory Hypertrophy in Paediatric Patients with a Unilateral Ureteropelvic Junction Obstruction.

BACKGROUND: Compensatory hypertrophy is common in children with solitary functioning kidney, but it is unknown whether it also develops in children with unilateral partial reduction of kidney function. OBJECTIVE: The aim of this study was to assess whether children with a unilateral ureteropelvic junction obstruction (UPJO) show compensatory growth of the unaffected kidney. Furthermore, we investigated whether the length of the unaffected kidney was related to the degree of split kidney function lost and other possible risk factors. Lastly, we studied a possible relationship with signs of kidney injury. DESIGN SETTING AND PARTICIPANTS: We retrospectively analysed clinical information from 194 children with a unilateral UPJO who participated in the Aetiologic research into Genetic and Occupational/environmental Risk factors for Anomalies in children (AGORA) data- and biobank. Data on kidney length, split kidney function, and other factors possibly associated with kidney length were extracted from electronic patient records. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Pearson's correlation coefficients between the split kidney function and unaffected kidney length were calculated. Multivariable logistic regression analyses were performed to identify factors associated with kidney length and signs of kidney injury. RESULTS AND LIMITATIONS: Most children with a UPJO had an unaffected kidney length above the reference for age at the end of follow-up (median age 6.5 yr). A correlation with split kidney function was present only in children with a split kidney function of ≥60% in the unaffected kidney (r = 0.41). Aside from split kidney function, UPJO side was the only determinant of kidney length, while no associations between kidney length and kidney injury were identified. CONCLUSIONS: Compensatory growth was visible in most children with a UPJO after sufficient follow-up time and was correlated with split kidney function in children with a severe UPJO. Contralateral kidney length provided no clear prognostic value for developing kidney injury. Studies with more patients and additional biomarkers of kidney injury are needed to further personalise care. PATIENT SUMMARY: Children with obstruction of urine outflow in one kidney often had a larger contralateral kidney. However, the size of this kidney could not be used to predict which children would develop kidney injury.

CDH12 as a Candidate Gene for Kidney Injury in Posterior Urethral Valve Cases: A Genome-wide Association Study Among Patients with Obstructive Uropathies.

BACKGROUND: Posterior urethral valves (PUVs) and ureteropelvic junction obstruction (UPJO) are congenital obstructive uropathies that may impair kidney development. OBJECTIVE: To identify genetic variants associated with kidney injury in patients with obstructive uropathy. DESIGN SETTING AND PARTICIPANTS: We included 487 patients born in 1981 or later who underwent pyeloplasty or valve resection before 18 yr of age in the discovery phase, 102 PUV patients in a first replication phase, and 102 in a second replication phase. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Signs of kidney injury were defined as dialysis, nephrectomy, kidney transplantation, estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2, high blood pressure, antihypertensive medication use, proteinuria, and/or one kidney functioning at <45%. We used χ2 tests to calculate p values and odds ratios for >600 000 single-nucleotide polymorphisms (SNPs) in the discovery sample comparing patients with and without signs of kidney injury within 5 yr after surgery. We performed stratified analyses for PUV and UPJO and Kaplan-Meier and Cox regression analyses in the discovery and two replication samples for the associated SNPs, and RNA and protein expression analyses for the associated gene in fetal tissues. RESULTS AND LIMITATIONS: Despite the small and nonhomogeneous sample, we observed suggestive associations for six SNPs in three loci, of which rs6874819 in the CDH12 gene was the most clear (p = 7.5 × 10-7). This SNP also seemed to be associated with time to kidney injury in the PUV discovery and replication samples. RNA expression analyses showed clear CDH12 expression in fetal kidneys, which was confirmed by protein immunolocalization. CONCLUSIONS: This study identified CDH12 as a candidate gene for kidney injury in PUV. PATIENT SUMMARY: We found that variants of the CDH12 gene increase the risk of kidney injury in patients with extra flaps of tissue in the urethra (posterior urethral valves). This is the first report on this gene in this context. Our study provides interesting new information about the pathways involved and important leads for further research for this condition.

Parents' expectations of the outpatient care for daytime urinary incontinence in children: A qualitative study.

INTRODUCTION: Daytime urinary incontinence (UI) can have an enormous impact on a child's life, lowering both self-esteem and quality of life. Although most children start therapy after their first visit to our outpatient clinic, no studies have reported on parents' or patients' expectations of care for daytime UI in this setting. OBJECTIVE: We aimed to explore the expectations of the parents of children referred to an outpatient clinic for daytime UI. STUDY DESIGN: This was a qualitative study that involved performing semi-structured interviews with the parents of children who had been referred for daytime UI (with or without nocturnal enuresis). Interviews took place between July 2018 and October 2018 and continued until saturation was reached. The results were transcribed verbatim and analyzed according to Giorgi's strategy of phenomenological data analysis. RESULTS: Nine parents of children, aged 5-12 years old, were interviewed, revealing "(Experienced) Health," Self-management," and "Social Impact" as the main themes that influenced parental expectations. All parents wanted to know if there was a medical explanation for UI, some were satisfied when diagnostics revealed no underlying condition, and others wanted treatment. Parents expressed no preferences about diagnostics or the content and duration of treatment, but they hoped that any previously attempted ineffective steps would not be repeated. Some parents defined treatment success as their child becoming completely dry, but most stated that learning coping strategies was more important. DISCUSSION: This is the first study to explore the expectations of parents when attending outpatient care for children with daytime UI. We employed a strong theoretical framework with a clear interview guide. The main limitations are that we only interviewed parents and that this was a qualitative study, precluding the drawing of firm conclusions. Nevertheless, our results point to the need for quantitative evaluation. CONCLUSION: Expectations seem to be influenced by (experienced) health, efforts at self-management, and the social impact of UI, making it critical that these themes are addressed. It was interesting to note that parents do not always attend outpatient departments with the goal of completely resolving daytime UI. Instead, some only want to know if there is an underlying medical condition or want to reduce the social impact by learning coping mechanisms. Excluding underlying medical conditions may therefore stimulate acceptance of watchful waiting without the need to start treatment.

What Do Men with Lower Urinary Tract Symptoms Expect from a Urologist in Secondary Care?

PURPOSE: To identify the expectations of men with LUTS referred to a urologist and to study the association between those expectations and satisfaction with the care provided. METHODS: In this prospective cohort study, adult men with LUTS completed a questionnaire before their first outpatient appointment, and again at 6 and 12 weeks. The questionnaires included IPSS and OABq-SF, and self-constructed questions on patient expectations, outcome of expectations and satisfaction. RESULTS: Data from 182 participants showed positive expectations about the urologist performing examinations, providing explanations and finding the underlying cause, but mostly neutral expectations for treatment plans and outcomes. Positive treatment expectations were associated with positive expectations about outcomes after physiotherapy, drug treatment and surgery. Higher symptom scores and age were associated with higher expectations about drug treatment. Expectations were subjectively and objectively fulfilled for 66.4% and 27.3%, respectively. Symptom improvement (decrease in IPSS scores) was significantly more in men with objectively fulfilled expectations than in men with no unfulfilled expectations. No significant difference was present between men with subjectively fulfilled expectations and men with unfulfilled expectations. However, satisfaction was significantly higher for patients with subjectively fulfilled expectations at 6 and 12 weeks compared with those who had unfulfilled expectations. CONCLUSION: Most men referred to a urologist with LUTS do express clear expectations about treatment in secondary care. Patients with higher expectations for treatment outcomes are more likely to expect to receive that treatment. Satisfaction with the care of a urologist is also higher when patients self-report that they receive the treatment they expected.

Determining the minimal important differences in the International Prostate Symptom Score and Overactive Bladder Questionnaire: results from an observational cohort study in Dutch primary care.

OBJECTIVES: To determine the minimal important difference (MID) of the International Prostate Symptom Score (IPSS) and the Overactive Bladder Questionnaire short form (OAB-q SF) assessed in primary care among patients treated for lower urinary tract symptoms (LUTS). DESIGN: Single-arm, open-label observational cohort study with a 6-week follow-up. SETTING: Twenty-two pharmacies in the Netherlands. PARTICIPANTS: We enrolled Dutch men with uncomplicated LUTS who received a new alpha-blocker prescription from their general practitioner or urologist. PRIMARY AND SECONDARY OUTCOMES: The IPSS and OAB-q SF were completed before and after 6 weeks of therapy. At 6 weeks, men also completed the Patient Global Impression of Improvement (PGI-I). The mean change scores of the IPSS and OAB-q SF were calculated for each PGI-I outcome category, with the category 'a little better' used to determine the MID. The SE of measurement (SEM) was calculated for each questionnaire. RESULTS: In total, 165 men completed follow-up. The MID was 5.2 points (95% CI 3.9 to 6.4; SEM 3.6) for the IPSS and 11.0 points (95% CI 7.1 to 14.9; SEM 9.7) for the OAB-q SF. For both questionnaires, CIs showed an overlap with the no-change categories. However, the MID for the IPSS was higher in men with severe baseline symptoms (7.1; 95% CI 5.3 to 9.0) than in men with moderate baseline symptoms (3.2; 95% CI 1.7 to 4.8). CONCLUSION: In this study, the MID for the IPSS was considerably higher than the MID of 3.1 reported in the only other study on this topic, but may be due to methodological differences. Interpretation of the MID for the OAB-q SF is hampered by the overlap with the SEM. Future studies are needed to confirm our results because correlations between the PGI-I and symptom questionnaires were suboptimal.

Discontinuation of alpha-blocker therapy in men with lower urinary tract symptoms: a systematic review and meta-analysis.

OBJECTIVES: We aimed to synthesise the available data for the effect of stopping alpha-blocker therapy among men with lower urinary tract symptoms. The focus was on symptom, uroflowmetry and quality of life outcomes, but we also reviewed the adverse events (AEs) and the number of patients who restarted therapy. DATA SOURCES: We searched MEDLINE/PubMed, EMBASE/Ovid and The Cochrane Central Register of Controlled Trials from inception to May 2018. ELIGIBILITY CRITERIA: We selected studies regardless of study design in which men were treated with an alpha-blocker for at least 3 months and in which the effects of alpha-blocker discontinuation were subsequently studied. Only controlled trials were used for the primary objective. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data and assessed the risk of bias for the controlled studies only using the Cochrane Collaboration's tool for assessing risk of bias. Data were pooled using random-effects meta-analyses. RESULTS: We identified 10 studies (1081 participants) assessing the primary objective. Six studies (733 participants) assessed differences in AEs between continuation and discontinuation, and six studies (501 participants) reported the numbers of subjects that restarted treatment after discontinuation. No studies in primary care were identified. After discontinuing monotherapy, symptom scores increased and peak flow rates decreased at 3 and 6 months, but not at 12 months; however, neither parameter changed when alpha-blockers were stopped during combination therapy. Small differences in post-void residual volumes and quality of life scores were considered clinically irrelevant. We also found that 0%-49% of patients restarted after stopping alpha-blocker therapy and that AEs did not increase with discontinuation. CONCLUSIONS: Discontinuing alpha-blocker monotherapy leads to a worsening compared with continuing therapy. Discontinuing the alpha-blocker after combination therapy had no significant effects on outcomes in either the short or long term. Discontinuation may be appropriate for the frail, elderly or those with concomitant illness or polypharmacy. However, studies in primary care are lacking. PROSPERO REGISTRATION NUMBER: CRD42016032648.

Effectiveness of a newly developed online self-management program for male patients with uncomplicated lower urinary tract symptoms.

AIMS: To explore the effect of an online self-management program in secondary care for men with lower urinary tract symptoms (LUTS). METHODS: We performed a prospective nonrandomized double-cohort pilot study of consecutive adult men referred with uncomplicated LUTS to three urology outpatient departments. Men in both cohorts received care as usual from a urologist, but men in the intervention cohort also had access to an online self-management program. Outcomes were assessed after 6 and 12 weeks: LUTS severity was assessed with the International Prostate Symptom Score (IPSS), the Overactive Bladder Questionnaire (OABq), and the Perceived Global Impression of Improvement (PGI-I). The main outcome of interest was a clear improvement in the PGI-I scores ("much better" or "very much better"). RESULTS: Age, symptom severity, and quality of life scores were comparable between the intervention (n = 113) and standard care (n = 54) cohorts. Clear improvement in the PGI-I scores was reported after 12 weeks in 19.4% and 26.1% of men in the intervention and standard care cohorts, respectively. However, logistic regression analysis indicated that the difference between cohorts was not significant. Multivariable linear regression analysis also indicated no significant differences between cohorts for the IPSS or the OABq score at either assessment point. Notably, the uptake of the intervention was low (53%). CONCLUSIONS: We found no significant benefit from adding an online self-management program to standard care for men with LUTS, probably due to the low uptake of the intervention that may have resulted from the timing in the care pathway.

Symptom improvement and predictors associated with improvement after 6 weeks of alpha-blocker therapy: An exploratory, single-arm, open-label cohort study.

OBJECTIVES: Clinicians should not only know how many patients will benefit from alpha-blocker therapy but should also be able to identify who will benefit. We studied the changes in patient symptoms following alpha-blocker therapy and the predictors of symptom improvement in clinical practice. DESIGN: This was a single-arm, open-label observational cohort study with a 6-week follow-up. SETTING: Twenty-two pharmacies in the Netherlands. PARTICIPANTS: Patients were eligible for inclusion if they attended a pharmacy with a new prescription for an alpha-blocker from a general practitioner or urologist. PRIMARY AND SECONDARY OUTCOMES: Outcomes were assessed using the International Prostate Symptom Score (IPSS), Overactive Bladder Questionnaire Short Form (OAB-q SF), and Patient Global Impression of Improvement (PGI-I). Demographic, disease-related, and drug-related information were collected to identify predictors of symptom improvement. These predictors were then assessed by logistic and linear regression analyses of both the original data set and an imputed data set that accounted for the missing variables. RESULTS: During the study, 37% of patients with lower urinary tract symptoms perceived clear symptomatic improvement based on the results of the PGI-I. Improvement was more likely in those who still used alpha-blockers at the end of the 6-week study period and in those who used multiple medications. Although symptom scores decreased significantly on the IPSS and OAB-q SF, the only predictor of change was the pretreatment symptom severity. CONCLUSIONS: Approximately one-third of our cohort perceived symptom improvement on alpha-blocker therapy. However, we identified no clear predictors of who might benefit from alpha-blocker treatment, indicating that alpha-blockers should still be prescribed on a trial basis.

Development of an online personalized self-management intervention for men with uncomplicated LUTS.

AIMS: To develop an online platform to facilitate evidence-based self-management of lower urinary tract symptoms (LUTS) in men. METHODS: Using the PubMed database (search until January 2017) and relevant guidelines, we reviewed evidence for the self-management of LUTS and identified suitable components for the intervention. Next, we built an algorithm that provided individualized advice based on patient characteristics and symptoms for use on an online platform. Men with LUTS tested the usability of the intervention and provided feedback. Finally, we surveyed urologists and general practitioners to identify potential areas for improvement of the intervention. RESULTS: We identified nine self-help interventions from 48 eligible publications. These were as follows: information and education about LUTS, pelvic floor muscle training, bladder training, urethral milking, double voiding, caffeine management, alcohol management, fluid management, and exercise advice. The level of evidence for each item was low due to the paucity of research available. Six men with LUTS reported difficulties understanding and completing the frequency-volume chart online. The 158 surveyed physicians agreed (≥50% positive ratings) on the inclusion of seven advice items, but not for double voiding and fluid management. Respondents noted that some advice should be provided to all men with LUTS, while other advice should only be presented to certain groups. Some recommendations for additions were offered. CONCLUSIONS: Despite a lack of evidence for the self-management advice, physicians agreed with most of the included advice. The online platform needs further development. Therefore, adjustments will be made and we will assess its impact in future studies.

Rare Variants in BNC2 Are Implicated in Autosomal-Dominant Congenital Lower Urinary-Tract Obstruction.

Congenital lower urinary-tract obstruction (LUTO) is caused by anatomical blockage of the bladder outflow tract or by functional impairment of urinary voiding. About three out of 10,000 pregnancies are affected. Although several monogenic causes of functional obstruction have been defined, it is unknown whether congenital LUTO caused by anatomical blockage has a monogenic cause. Exome sequencing in a family with four affected individuals with anatomical blockage of the urethra identified a rare nonsense variant (c.2557C>T [p.Arg853∗]) in BNC2, encoding basonuclin 2, tracking with LUTO over three generations. Re-sequencing BNC2 in 697 individuals with LUTO revealed three further independent missense variants in three unrelated families. In human and mouse embryogenesis, basonuclin 2 was detected in lower urinary-tract rudiments. In zebrafish embryos, bnc2 was expressed in the pronephric duct and cloaca, analogs of the mammalian lower urinary tract. Experimental knockdown of Bnc2 in zebrafish caused pronephric-outlet obstruction and cloacal dilatation, phenocopying human congenital LUTO. Collectively, these results support the conclusion that variants in BNC2 are strongly implicated in LUTO etiology as a result of anatomical blockage.