Diagnoses and Treatment Recommendations-Interrater Reliability of Uroflowmetry in People with Multiple Sclerosis.

BACKGROUND: Uroflowmetry (UF) is an established procedure in urology and is recommended before further investigations of neurogenic lower urinary tract dysfunction (NLUTD). Some authors even consider using UF instead of urodynamics (UD). Studies on the interrater reliability of UF regarding treatment recommendations are rare, and there are no relevant data on people with multiple sclerosis (PwMS). The aim of this study was to investigate the interrater reliability (IRR) of UF concerning diagnosis and therapy in PwMS prospectively. METHODS: UF of 92 PwMS were assessed by 4 raters. The diagnostic criteria were normal findings (NFs), detrusor overactivity (DO), detrusor underactivity (DU), detrusor-sphincter dyssynergia (DSD) and bladder outlet obstruction (BOO). The possible treatment criteria were as follows: no treatment (NO), catheter placement (CAT), alpha-blockers, detrusor-attenuating medication, botulinum toxin (BTX), neuromodulation (NM), and physiotherapy/biofeedback (P/BF). IRR was assessed by kappa (κ). RESULTS: κ of diagnoses were NFs = 0.22; DO = 0.17; DU = 0.07; DSD = 0.14; and BOO = 0.18. For therapies, the highest κ was BTX = 0.71, NO = 0.38 and CAT = 0.44. CONCLUSIONS: There is a high influence of the individual rater. UD should be subject to the same analysis and a comparison should be made between UD and UF. This may have implications for the value of UF in the neuro-urological management of PwMS, although at present UD remains the gold standard for the diagnostics of NLUTD in PwMS.

Risk factors of bladder stones in neurogenic lower urinary tract dysfunction: A real-world study.

Objective: The objective of this study is to investigate the incidence and risk factors for stone formation and recurrence in patients with neurogenic lower urinary tract dysfunction (NLUTD) in a real-world cohort. Materials and methods: A retrospective cohort study was conducted on all patients with NLUTD who underwent bladder stone treatment between 2010 and 2022. Univariate and multivariate Cox models were used to identify the potential risk factors for stone recurrence. Results: Among 114 patients included in the study, 30% experienced stone recurrence. The most common stone components were carbonate apatite phosphate and magnesium ammonium phosphate. The overall recurrence rate was 14 cases per 100 patient years. Neurogenic detrusor overactivity had the highest recurrence rate. Risk factors for stone recurrence in the multivariate analysis were intermittent and suprapubic catheterization, and recurrent urinary tract infection (rUTI). Conclusions: Patients experienced multiple bladder stone recurrences. Close monitoring of bladder pressure and UTI with restrictive catheter application may reduce the risk of stone recurrence.

The Efficacy and Safety of Intrasphincteric Botulinum Toxin-A Injections in Patients with Non-Spinal Cord Injury-Related Detrusor Sphincter Dyssynergia: A Retrospective Study.

Botulinum toxin-A (BoNT-A) injections into the external urethral sphincter are an established therapeutic procedure for reducing bladder outlet obstruction in patients with detrusor sphincter dyssynergia (DSD) due to spinal cord injury (SCI). Given the paucity of data on patients with DSD but without SCI, we aimed to assess the efficacy of intrasphincteric BoNT-A injections in this cohort. For this retrospective study, we screened all patients who underwent their first intrasphincteric BoNT-A injection at our institution between 2015 and 2021. The inclusion criteria were patients aged 18 years or older with neurogenic detrusor overactivity (NDO) and DSD with a maximum detrusor pressure (Pdetmax) of >40 cmH2O, confirmed via video-urodynamic studies (VUDS). The primary outcome was a reduction in Pdetmax and detrusor overactivity leak point pressure (DOLPP) during NDO-associated urinary incontinence posttreatment. The secondary outcome was a reduction in patients relying on indwelling urinary catheters posttreatment. We included 13 eligible patients (all male, median age 31 years, with different underlying neurological disorders, except SCI). All underwent intrasphincteric BoNT-A injections with either 100 (n = 7) or 150 (n = 6) units, respectively. Pdetmax during voiding was significantly reduced posttreatment (median 105 vs. 54 cmH2O, p = 0.006), whereas DOLPP remained unchanged (i.e., median 50 cmH2O). While seven patients relied on indwelling urinary catheters pre-treatment, all were catheter-free posttreatment. Intrasphincteric BoNT-A injections in patients with non-SCI related DSD appear feasible for reducing bladder outlet obstruction to a certain degree in this cohort and subsequently for reducing the rate of indwelling catheters.

Prevalence of Unfavorable Video-Urodynamic Findings and Clinical Implications in Patients with Minimally Conscious State/Unresponsive Wakefulness Syndrome: A Retrospective Descriptive Analysis.

The aim of this retrospective exploratory study was to investigate the prevalence of unfavorable findings during video-urodynamic studies (VUDS) in patients with minimally conscious state (MCS)/unresponsive wakefulness syndrome (UWS) and whether management of the lower urinary tract (LUT) was adjusted accordingly. A retrospective chart review was conducted to screen for patients diagnosed with MCS/UWS at our rehabilitation center between 2011 and 2020. Patients 18 years or older were included and underwent baseline VUDS after being diagnosed with MCS/UWS. We analyzed urodynamic parameters and subsequent changes in LUT management in this cohort. In total, 32 patients (7 females, 25 males, median age 37 years) with MCS/UWS were included for analysis. While at least one unfavorable VUDS finding (i.e., neurogenic detrusor overactivity [NDO], detrusor sphincter dyssynergia {DSD, high maximum detrusor pressure during storage phase [>40 cmH2O], low-compliance bladder [<20 mL/cmH2O], and vesico-uretero-renal reflux [VUR]) was found in each patient, NDO (78.1%, 25/32) and DSD (68.8%, 22/32) were the two most frequent unfavorable VUDS findings. Following baseline VUDS, new LUT treatment options were established in 56.3% (18/32) of all patients. In addition, bladder-emptying methods were changed in 46.9% (15/32) of all patients, resulting in fewer patients relying on indwelling catheters. Our retrospective exploratory study revealed a high prevalence of NDO and DSD in patients with MCS/UWS, illustrating the importance of VUDS to adapt LUT management in this cohort accordingly.

Sex differences in urological management during spinal cord injury rehabilitation: results from a prospective multicenter longitudinal cohort study.

STUDY DESIGN: Prospective, multicenter, longitudinal cohort study. OBJECTIVES: To describe female-male differences in first-line urological management during spinal cord injury (SCI) rehabilitation. SETTING: Inpatient specialized post-acute SCI rehabilitation in Switzerland. METHODS: Data on bladder storage medication (antimuscarinic and beta-3 agonist) use, suprapubic catheter placement, demographic and SCI characteristics was collected within 40 days of SCI and at rehabilitation discharge from May 2013-September 2021. Prevalence and indicators of bladder storage medication and suprapubic catheter use at discharge were investigated with sex-stratified descriptive and logistic regression analyses. RESULTS: In 748 patients (219 females, 29%), bladder storage medication use at discharge had a prevalence of 24% (95% CI: 18-29%) for females and 30% (95% CI: 26-34%) for males and was indicated by cervical AIS grade A, B, C and traumatic SCI in both sexes. Thoracic AIS grade A, B, C SCI (males), and lumbar/sacral AIS grade A, B, C SCI (females) predicted higher odds of bladder storage medication use (SCI characteristic*sex interaction, p < 0.01). Prevalence of suprapubic catheter use at discharge was 22% (95% CI: 17-28%) for females and 17% (95% CI: 14-20%) for males. Suprapubic catheter use was indicated by cervical AIS grade A, B, C SCI, and age >60 in both sexes. Females with thoracic grade A, B, C SCI tended to have higher odds of suprapubic catheter use (SCI characteristic*sex interaction, p = 0.013). CONCLUSIONS: We identified sex differences in urological management especially in persons with AIS grade C or higher sub-cervical SCI. There is scope for well-powered, female-specific research in SCI in order to understand the underlying mechanisms and support patient-tailored management.

Urological Management at Discharge from Acute Spinal Cord Injury Rehabilitation: A Descriptive Analysis from a Population-based Prospective Cohort.

Background: There is limited epidemiological evidence describing contemporary neuro-urological management of persons with acute spinal cord injury (SCI). Objective: To describe neurogenic lower urinary tract dysfunction (NLUTD) management at discharge from SCI rehabilitation. Design setting and participants: The population-based Swiss Spinal Cord Injury (SwiSCI) cohort study prospectively collected data from 602 adults undergoing specialized postacute SCI rehabilitation from 2013 to 2020. The management strategy was based on the European Association of Urology (EAU) Guidelines on Neuro-Urology. Outcome measurements and statistical analysis: Data were collected at discharge using the International SCI Lower Urinary Tract Function Basic Data Set. Multivariable logistic regression adjusting for demographics, SCI characteristics, and center, with inverse probability weighting accounting for sampling bias, was used to produce prevalence estimates and identify predictors of lower urinary tract symptoms (LUTS) and NLUTD management outcomes. Results and limitations: At discharge (median time after SCI: 5.0 mo [Q1-Q3: 3.0-7.2]), the prevalence of LUTS or managed NLUTD was 82% (95% confidence interval [CI]: 79-85%). SCI completeness was the main predictor of LUTS and managed NLUTD. The risk of urinary incontinence was elevated in females (odds ratio 1.98 [95% CI: 1.18-3.32]) and with complete lesions (odds ratio 4.71 [95% CI: 2.52-8.81]). Voiding dysfunction was most commonly managed with intermittent catheterization (prevalence 39% [95% CI: 35-42%]), followed by indwelling catheterization (prevalence 22% [95% CI: 18-25%]). The prevalence of antimuscarinic or mirabegron use was 29% (95% CI: 26-33%). Urodynamic and renal function data were not collected. Conclusions: Our population-based description of urological management in Swiss SCI centers utilizing the EAU Guidelines on Neuro-Urology may be used as a reference for evaluation in other settings. Data further indicate a need for sex-specific neuro-urological management research. Patient summary: At discharge from spinal cord injury (SCI) rehabilitation, a majority of patients have lower urinary tract problems, especially those with complete SCI. Women have a higher risk of urinary incontinence.

The alternative serotonin transporter promoter P2 impacts gene function in females with irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a gut-brain disorder in which symptoms are shaped by serotonin acting centrally and peripherally. The serotonin transporter gene SLC6A4 has been implicated in IBS pathophysiology, but the underlying genetic mechanisms remain unclear. We sequenced the alternative P2 promoter driving intestinal SLC6A4 expression and identified single nucleotide polymorphisms (SNPs) that were associated with IBS in a discovery sample. Identified SNPs built different haplotypes, and the tagging SNP rs2020938 seems to associate with constipation-predominant IBS (IBS-C) in females. rs2020938 validation was performed in 1978 additional IBS patients and 6,038 controls from eight countries. Meta-analysis on data from 2,175 IBS patients and 6,128 controls confirmed the association with female IBS-C. Expression analyses revealed that the P2 promoter drives SLC6A4 expression primarily in the small intestine. Gene reporter assays showed a functional impact of SNPs in the P2 region. In silico analysis of the polymorphic promoter indicated differential expression regulation. Further follow-up revealed that the major allele of the tagging SNP rs2020938 correlates with differential SLC6A4 expression in the jejunum and with stool consistency, indicating functional relevance. Our data consolidate rs2020938 as a functional SNP associated with IBS-C risk in females, underlining the relevance of SLC6A4 in IBS pathogenesis.

Optimizing clinical trial design using prospective cohort study data: a case study in neuro-urology.

STUDY DESIGN: Simulations using data from a prospective cohort study. OBJECTIVES: To illustrate how prospective cohort data can be employed in randomized controlled trial (RCT) planning to assess feasibility and operational challenges, using TASCI (Transcutaneous tibial nerve stimulation in patients with Acute Spinal Cord Injury to prevent neurogenic detrusor overactivity: a nationwide randomized, sham-controlled, double-blind clinical trial) as a case study. SETTING: Spinal cord injury (SCI) rehabilitation centers in Switzerland. METHODS: TASCI is nested in the multicenter Swiss Spinal Cord Injury Cohort Study (SwiSCI), which prospectively includes patients with acute SCI. In simulations, data from 640 patients, collected by SwiSCI, were used to investigate different scenarios of patient eligibility and study consent, as well as the performance of the randomization list. Descriptive analysis was used to describe the population of interest and the simulation results; multivariable logistic regression analysis was performed to identify predictors of discharge within the TASCI intervention time period. RESULTS: The recruitment target of 114 patients is obtainable within the originally envisioned 3-year time period under the most favorable recruitment scenario examined. The distribution of the primary prognostic factor produced imbalance in the randomization lists and informed further discussion of the cut-off values used in stratification. Influxes of patients resulted in overlapping intervention periods for multiple participants, which guided resource allocation. Early discharge was related to the primary prognostic factor and study center, but is only anticipated in about 8% of participants. CONCLUSIONS: Prospective cohort data are a very valuable resource for planning RCTs.

TASCI-transcutaneous tibial nerve stimulation in patients with acute spinal cord injury to prevent neurogenic detrusor overactivity: protocol for a nationwide, randomised, sham-controlled, double-blind clinical trial.

INTRODUCTION: Neurogenic lower urinary tract dysfunction (NLUTD), including neurogenic detrusor overactivity (NDO) and detrusor sphincter dyssynergia, is one of the most frequent and devastating sequelae of spinal cord injury (SCI), as it can lead to urinary incontinence and secondary damage such as renal failure. Transcutaneous tibial nerve stimulation (TTNS) is a promising, non-invasive neuromodulatory intervention that may prevent the emergence of the C-fibre evoked bladder reflexes that are thought to cause NDO. This paper presents the protocol for TTNS in acute SCI (TASCI), which will evaluate the efficacy of TTNS in preventing NDO. Furthermore, TASCI will provide insight into the mechanisms underlying TTNS, and the course of NLUTD development after SCI. METHODS AND ANALYSIS: TASCI is a nationwide, randomised, sham-controlled, double-blind clinical trial, conducted at all four SCI centres in Switzerland. The longitudinal design includes a baseline assessment period 5-39 days after acute SCI and follow-up assessments occurring 3, 6 and 12 months after SCI. A planned 114 participants will be randomised into verum or sham TTNS groups (1:1 ratio), stratified on study centre and lower extremity motor score. TTNS is performed for 30 min/day, 5 days/week, for 6-9 weeks starting within 40 days after SCI. The primary outcome is the occurrence of NDO jeopardising the upper urinary tract at 1 year after SCI, assessed by urodynamic investigation. Secondary outcome measures assess bladder and bowel function and symptoms, sexual function, neurological structure and function, functional independence, quality of life, as well as changes in biomarkers in the urine, blood, stool and bladder tissue. Safety of TTNS is the tertiary outcome. ETHICS AND DISSEMINATION: TASCI is approved by the Swiss Ethics Committee for Northwest/Central Switzerland, the Swiss Ethics Committee Vaud and the Swiss Ethics Committee Zürich (#2019-00074). Findings will be disseminated through peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT03965299.

Tolerability and safety of urotainer® polihexanide 0.02% in catheterized patients: a prospective cohort study.

BACKGROUND: In patients with indwelling bladder catheters for > 2 weeks, bacterial colonization is inevitable, leading to urinary tract infections or encrustations with subsequent catheter blockage. Currently, bladder irrigations are the most frequently used prophylactic means, but the best solution remains yet to be determined. In vitro studies demonstrate that polihexanide is a promising option for catheter irrigation, but no data about safety and tolerability exist. METHODS: In a prospective observational study in patients with indwelling bladder catheter for > 2 weeks, a 0.02% polihexanide solution was used to rinse the catheter on five consecutive days. Adverse events, tolerability and vital signs were assessed before, during, after and at the end of the treatment period. RESULTS: There was no serious adverse event in the study. A total of 28 adverse events (AEs) in 15 (46.88%) participants were experienced. Absolute changes in pain scores were not clinically relevant. No incidences of either flushing or sweating were found during instillation. Bladder spasms during instillation were reported in two cases during a single instillation. Mean pulse rates did not change by more than 3 beats per minute. Mean changes in body temperature did not exceed 0.12 °C. Clinically relevant changes in blood pressure were recorded for 3 patients. CONCLUSIONS: This is the first study to demonstrate that a 0.02% polihexanide solution can safely be used for catheter irrigation. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT02157415 ), June 6th, 2014.

Update from TASCI, a Nationwide, Randomized, Sham-controlled, Double-blind Clinical Trial on Transcutaneous Tibial Nerve Stimulation in Patients with Acute Spinal Cord Injury to Prevent Neurogenic Detrusor Overactivity.

Transcutaneous tibial nerve stimulation has the potential to revolutionize the management of lower urinary tract dysfunction in patients with acute spinal cord injury. TASCI is a nationwide randomized, sham-controlled, double-blind clinical trial for which the preparatory phase has been successfully completed.

Bladder emptying method is the primary determinant of urinary tract infections in patients with spinal cord injury: results from a prospective rehabilitation cohort study.

OBJECTIVE: To understand the occurrence of and risk factors for urinary tract infections (UTIs) in patients with spinal cord injury (SCI) undergoing specialized SCI rehabilitation in Switzerland. PATIENTS AND METHODS: This study used data collected from 369 patients, who participated in a nationwide rehabilitation cohort for SCI in Switzerland between 2013 and 2017. Information on UTIs as well as their potential determinants, including demographics, lesion characteristics, and time-updated data on functional independence and bladder management, was used. Multivariable regression methods were applied to perform a time-updated evaluation of determinants of UTI risk. RESULTS: The crude incidence rate (IR) of UTIs was 0.55 UTIs per 100 person-days (95% confidence interval [CI] 0.49-0.62), the cumulative IR was 43%, and the median length of stay was 122 days. The bladder emptying method at discharge was largely determined by 28 days after admission. Among those using indwelling or assisted intermittent catheterization (IC), the likelihood of self-IC at discharge was positively related to the level of self-care independence, negatively related to age at injury, and lower in women than men. Catheter users consistently had higher adjusted IRs for UTI than spontaneous voiders. The IR ratios were: indwelling catheter: 5.97 (95% CI 2.63-13.57); assisted IC: 6.05 (95% CI 2.63-13.94); self-IC: 5.16 (95% CI 2.31-11.52); test for differences across catheter groups: P = 0.82. Lesion severity and previous UTI had additional but smaller effect sizes. CONCLUSIONS: Bladder emptying method was identified as the main risk factor for UTI in patients with SCI. As spontaneous voiders had the lowest UTI rate, further research is warranted to reduce voiding dysfunction, for instance using neuromodulation procedures.

Physician-led, hospital-linked, birth care centers can decrease cesarean section rates without increasing rates of adverse events.

BACKGROUND: This study compares outcomes at a hospital-linked, physician-led, birthing center to a traditional hospital labor and delivery service. METHODS: Using de-identified electronic medical records, a retrospective cohort design was employed to evaluate 32,174 singleton births during 1998-2005. RESULTS: Compared with hospital service, birth care center delivery was associated with a lower rate of cesarean sections (adjusted Relative Risk = 0.73, 95% confidence interval 0.59-0.91; p < 0.001) without an increased rate of operative vaginal delivery (adjusted Relative Risk = 1.04, 95% confidence interval 0.97-1.13; p = 0.25) and a higher initiation of breastfeeding (adjusted Relative Risk = 1.28, 95% confidence interval 1.25-1.30; p ≤ 0.001). A maternal length of stay greater than 72 hours occurred less frequently in the birth care center (adjusted Relative Risk = 0.60, 95% confidence interval 0.55-0.66; p < 0.001). Comparing only women without major obstetrical risk factors, the differences in outcomes were reduced but not eliminated. Adverse maternal and infant outcomes were not increased at the birth care center. CONCLUSION: A hospital-linked, physician-led, birth care center has the potential to lower rates of cesarean sections without increasing rates of operative vaginal delivery or other adverse maternal and infant outcomes.

Protecting contract workers: case study of the US Department of Energy's nuclear and chemical waste management.

Increased reliance on subcontractors in all economic sectors is a serious occupational health and safety challenge. Short-term cost savings are offset by long-term liability. Hiring subcontractors brings specialized knowledge but also young, inexperienced, inadequately trained workers onto industrial and hazardous waste sites, which leads to increased rates of accidents and injuries. Reliable data on subcontractor occupational health and safety programs and performance are sparse. The US Department of Energy has an excellent safety culture on paper, but procurement practices and contract language deliver a mixed message--including some safety disincentives. Its biphasic safety outcome data are consistent with underreporting by some subcontractors and underachievement by others. These observations are relevant to the private and public sectors. Occupational health and safety should be viewed as an asset, not merely a cost.

Pharmacokinetics of tea catechins after ingestion of green tea and (-)-epigallocatechin-3-gallate by humans: formation of different metabolites and individual variability.

Green tea and tea polyphenols have been studied extensively as cancer chemopreventive agents in recent years. The bioavailability and metabolic fate of tea polyphenols in humans, however, are not clearly understood. In this report, the pharmacokinetic parameters of (-)-epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin (EGC), and (-)-epicatechin (EC) were analyzed after administration of a single oral dose of green tea or decaffeinated green tea (20 mg tea solids/kg) or EGCG (2 mg/kg) to eight subjects. The plasma and urine levels of total EGCG, EGC, and EC (free plus conjugated forms) were quantified by HPLC coupled to an electrochemical detector. The plasma concentration time curves of the catechins were fitted in a one-compartment model. The maximum plasma concentrations of EGCG, EGC, and EC in the three repeated experiments with green tea were 77.9 +/- 22.2, 223.4 +/- 35.2, and 124.03 +/- 7.86 ng/ml, respectively, and the corresponding AUC values were 508.2 +/- 227, 945.4 +/- 438.4, and 529.5 +/- 244.4 ng x h x ml(-1), respectively. The time needed to reach the peak concentrations was in the range of 1.3-1.6 h. The elimination half-lives were 3.4 +/- 0.3, 1.7 +/- 0.4, and 2.0 +/- 0.4 h, respectively. Considerable interindividual differences and variations between repeated experiments in the pharmacokinetic parameters were noted. Significant differences in these pharmacokinetic parameters were not observed when EGCG was given in decaffeinated green tea or in pure form. In the plasma, EGCG was mostly present in the free form, whereas EGC and EC were mostly in the conjugated form. Over 90% of the total urinary EGC and EC, almost all in the conjugated forms, were excreted between 0 and 8 h. Substantial amounts of 4'-O-methyl EGC, at levels higher than EGC, were detected in the urine and plasma. The plasma level of 4'-O-methyl EGC peaked at 1.7 +/- 0.5 h with a half life of 4.4 +/- 1.1 h. Two ring-fission metabolites, (-)-5-(3',4',5'-trihydroxyphenyl)-gamma-valerolactone (M4) and (-)-5-(3',4'-dihydroxyphenyl)-valerolactone (M6), appeared in significant amounts after 3 h and peaked at 8-15 h in the urine as well as in the plasma. These results may be useful for designing the dose and dose frequency in intervention studies with tea and for development of biomarkers of tea consumption.