The patient pathway for overactive bladder management:A quantitative analysis

PURPOSE: We aimed to explore the pathways followed by patients with overactive bladder (OAB) from referral to the urologist to final treatment. METHODS: This was a single-center, retrospective cohort study of female patients diagnosed with OAB in a large Dutch nonacademic teaching hospital. The number, sequence, and duration of treatment steps offered were analyzed, and the effectiveness, reasons for discontinuation, and possible case-mix variables influencing OAB treatment were studied. RESULTS: In total, 120 patients were enrolled and required a median of 2 steps (range, 1-6) of treatment over a median total duration of 28 weeks (range, 5-256). Treatment typically started with drug therapy, including antimuscarinics (38%; 95% CI, 30%-47%), antimuscarinics plus pelvic floor muscle therapy (21%; 95% CI, 15%-29%), or mirabegron (11%; 95% CI, 6%-18%). However, 52% of patients required further treatment, with botulinum toxin A (BoNT-A) injections being most effective (67%; 95% CI, 42%-85%), followed by antimuscarinics plus percutaneous tibial nerve stimulation (50%; 95% CI, 25%-75%), and antimuscarinics plus pelvic floor muscle therapy (36%; 95% CI, 21%-54%). Other therapies showed lower effectiveness. Common reasons for discontinuation were insufficient response and side effects. Overall, 22 patients were lost to follow-up. CONCLUSION: Most patients try at least two treatments before they experience satisfactory symptom relief, with treatment evaluations requiring time because therapeutic onsets differ by patient and treatment. Our data can help to manage expectations among urologists and patients when seeking treatment for OAB

Different Aspects of Classical Pathway Overactivation in Patients With C3 Glomerulopathy and Immune Complex-Mediated Membranoproliferative Glomerulonephritis

The rare and heterogeneous kidney disorder C3 glomerulopathy (C3G) is characterized by dysregulation of the alternative pathway (AP) of the complement system. C3G is often associated with autoantibodies stabilizing the AP C3 convertase named C3 nephritic factors (C3NeF). The role of classical pathway (CP) convertase stabilization in C3G and related diseases such as immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) remains largely unknown. Here, we investigated the CP convertase activity in patients with C3G and IC-MPGN. Using a refined two-step hemolytic assay, we measured the stability of CP convertases directly in the serum of 52 patients and 17 healthy controls. In four patients, CP convertase activity was prolonged compared to healthy controls, i.e. the enzymatic complex was stabilized. In three patients (2 C3G, 1 IC-MPGN) the convertase stabilization was caused by immunoglobulins, indicating the presence of autoantibodies named C4 nephritic factors (C4NeFs). Importantly, the assay also enabled detection of non-immunoglobulin-mediated stabilization of the CP convertase in one patient with C3G. Prolonged CP convertase activity coincided with C3NeF activity in all patients and for up to 70 months of observation. Crucially, experiments with C3-depleted serum showed that C4NeFs stabilized the CP C3 convertase (C4bC2a), that does not contain C3NeF epitopes. All patients with prolonged CP convertase activity showed clear signs of complement activation, i.e. lowered C3 and C5 levels and elevated levels of C3d, C3bc, C3bBbP, and C5b-9. In conclusion, this work provides new insights into the diverse aspects and (non-)immunoglobulin nature of factors causing CP convertase overactivity in C3G/IC-MPGN.</p

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

Exploring pelvic floor muscle activity in men with lower urinary tract symptoms

Aim We aimed to explore the utility of the Multiple Array Probe Leiden (MAPLe) device to assess pelvic floor muscle activity in men with lower urinary tract symptoms (LUTS). Methods This was an observational cohort study performed at the urology outpatient department of a large teaching hospital in the Netherlands between April and October 2018. We recruited male patients referred for the assessment of LUTS, without a history of prostate surgery, if they had an International Prostate Symptom Score greater than or equal to 8. The MAPLe device was then used to assess the puborectalis, pubococcygeus, iliococcygeus, urogenital diaphragm, and the internal and external anal sphincters during three tasks: a rest period (1 minute), five maximum voluntary contractions (held for 3 seconds each), and three maximal endurance contractions (held for 15 seconds each). Results In total, 57 patients were included, 5 of which had diabetes mellitus. Muscle activity at rest was significantly lower than during either contraction task and did not differ between the muscle groups. By contrast, the external anal sphincter had significantly less activity than any other muscle group during the endurance task, and the internal anal sphincter and puborectalis had significantly less activity during the maximum voluntary contraction task. No association was found between pelvic floor muscle activity and LUTS severity during any task. Conclusion Pelvic floor muscle activity and LUTS severity appear to be unrelated, but this does not completely exclude the possibility of muscle involvement in the development or experience of symptoms. Further research is needed

Hospital volume is associated with postoperative mortality after radical cystectomy for treatment of bladder cancer

Contains fulltext : 237666.pdf (Publisher’s version ) (Open Access)OBJECTIVE: To contribute to the debate regarding the minimum volume of radical cystectomies (RCs) that a hospital should perform by evaluating the association between hospital volume (HV) and postoperative mortality. PATIENTS AND METHODS: Patients who underwent RC for bladder cancer between 1 January 2008 and 31 December 2018 were retrospectively identified from the Netherlands Cancer Registry. To create a calendar-year independent measure, the HV of RCs was calculated per patient by counting the RCs performed in the same hospital in the 12 months preceding surgery. The relationship of HV with 30- and 90-day mortality was assessed by logistic regression with a non-linear spline function for HV as a continuous variable, which was adjusted for age, tumour, node and metastasis (TNM) stage, and neoadjuvant treatment. RESULTS: The median (interquartile range; range) HV among the 9287 RC-treated patients was 19 (12-27; 1-75). Of all the included patients, 208 (2.2%) and 518 (5.6%) died within 30 and 90 days after RC, respectively. After adjustment for age, TNM stage and neoadjuvant therapy, postoperative mortality slightly increased between an HV of 0 and an HV of 25 RCs and steadily decreased from an HV of 30 onwards. The lowest risks of postoperative mortality were observed for the highest volumes. CONCLUSION: This paper, based on high-quality data from a large nationwide population-based cohort, suggests that increasing the RC volume criteria beyond 30 RCs annually could further decrease postoperative mortality. Based on these results, the volume criterion of 20 RCs annually, as recently recommended by the European Association of Urology Guideline Panel, might therefore be reconsidered

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

Common Genetic Variants, Acting Additively, Are a Major Source of Risk for Autism

Background: Autism spectrum disorders (ASD) are early onset neurodevelopmental syndromes typified by impairments in reciprocal social interaction and communication, accompanied by restricted and repetitive behaviors. While rare and especially de novo genetic variation are known to affect liability, whether common genetic polymorphism plays a substantial role is an open question and the relative contribution of genes and environment is contentious. It is probable that the relative contributions of rare and common variation, as well as environment, differs between ASD families having only a single affected individual (simplex) versus multiplex families who have two or more affected individuals. Methods: By using quantitative genetics techniques and the contrast of ASD subjects to controls, we estimate what portion of liability can be explained by additive genetic effects, known as narrow-sense heritability. We evaluate relatives of ASD subjects using the same methods to evaluate the assumptions of the additive model and partition families by simplex/multiplex status to determine how heritability changes with status. Results: By analyzing common variation throughout the genome, we show that common genetic polymorphism exerts substantial additive genetic effects on ASD liability and that simplex/multiplex family status has an impact on the identified composition of that risk. As a fraction of the total variation in liability, the estimated narrow-sense heritability exceeds 60% for ASD individuals from multiplex families and is approximately 40% for simplex families. By analyzing parents, unaffected siblings and alleles not transmitted from parents to their affected children, we conclude that the data for simplex ASD families follow the expectation for additive models closely. The data from multiplex families deviate somewhat from an additive model, possibly due to parental assortative mating. Conclusions: Our results, when viewed in the context of results from genome-wide association studies, demonstrate that a myriad of common variants of very small effect impacts ASD liability

Epidemiology of Bladder Cancer in 2023: A Systematic Review of Risk Factors

CONTEXT Bladder cancer (BC) is common worldwide and poses a significant public health challenge. External risk factors and the wider exposome (totality of exposure from external and internal factors) contribute significantly to the development of BC. Therefore, establishing a clear understanding of these risk factors is the key to prevention. OBJECTIVE To perform an up-to-date systematic review of BC's epidemiology and external risk factors. EVIDENCE ACQUISITION Two reviewers (I.J. and S.O.) performed a systematic review using PubMed and Embase in January 2022 and updated it in September 2022. The search was restricted to 4 yr since our previous review in 2018. EVIDENCE SYNTHESIS Our search identified 5177 articles and a total of 349 full-text manuscripts. GLOBOCAN data from 2020 revealed an incidence of 573 000 new BC cases and 213 000 deaths worldwide in 2020. The 5-yr prevalence worldwide in 2020 was 1 721 000. Tobacco smoking and occupational exposures (aromatic amines and polycyclic aromatic hydrocarbons) are the most substantial risk factors. In addition, correlative evidence exists for several risk factors, including specific dietary factors, imbalanced microbiome, gene-environment risk factor interactions, diesel exhaust emission exposure, and pelvic radiotherapy. CONCLUSIONS We present a contemporary overview of the epidemiology of BC and the current evidence for BC risk factors. Smoking and specific occupational exposures are the most established risk factors. There is emerging evidence for specific dietary factors, imbalanced microbiome, gene-external risk factor interactions, diesel exhaust emission exposure, and pelvic radiotherapy. Further high-quality evidence is required to confirm initial findings and further understand cancer prevention. PATIENT SUMMARY Bladder cancer is common, and the most substantial risk factors are smoking and workplace exposure to suspected carcinogens. On-going research to identify avoidable risk factors could reduce the number of people who get bladder cancer