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

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

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

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

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Genetic insights into resting heart rate and its role in cardiovascular disease

Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development

Cholinergic innervation and muscarinic receptors in the human prostate

Objective: in light of recent interest in the use of muscarinic receptor antagonists for the treatment of male lower urinary tract symptoms, understanding how such drugs work not only on the bladder but also on the prostate is important. Methods: A literature review was conducted to identify studies on the cholinergic innervation and presence and function of muscarinic acetylcholine receptors in the human prostate. Results: The available studies demonstrate a dense cholinergic innervation within both stromal. and epithelial compartments of the prostate. Concomitantly, the human prostate expresses muscarinic receptors at densities exceeding those of alpha(1)-adrenoceptors. They mainly belong to the M-1 subtype and are found on epithelial cells, but a smaller population of M-2 receptors is found on stromal cells. Both populations have been shown to be functional in signal transduction assays. However, in line with the sparse receptor density on stromal smooth muscle cells, contractile responses of the prostate are only small. Data from prostate cancer cell lines and from botulinum toxin injections into the benign prostate raise the possibility that muscarinic receptors may promote prostatic growth. Animal data suggest that muscarinic receptors may be of primary importance in the genesis of prostatic secretions, but this needs to be confirmed in humans. Conclusions: Taken together it appears that direct effects on the prostate need to be considered when using muscarinic receptor antagonists in men. They may primarily involve alterations of glandular secretion and prostatic growth. (C) 2008 European Association of Urology. Published by Elsevier B.V. All rights reserve