Transcutaneous Tibial Nerve Stimulation for Urge Incontinence: A Randomized Clinical Trial.

Importance: Overactive bladder is a distressing syndrome that significantly affects quality of life. Transcutaneous tibial nerve stimulation (TTNS) has been proposed as a home-based, patient-centered therapy that could improve access to treatment for this condition.

Objective: We aimed to determine the efficacy of 12 weeks of TTNS versus sham therapy in reducing symptomatic bother in ambulatory women with urgency urinary incontinence.

A prospective study to assess the effectiveness and safety of the BlueWind System in the treatment of patients diagnosed with urgency urinary incontinence.

Background: Overactive bladder (OAB) affects one in six adults in Europe and the United States and impairs the quality of life of millions of individuals worldwide. When conservative management fails, third-line treatments including tibial neuromodulation (TNM) is often pursued. TNM has traditionally been accomplished percutaneously in clinic.

Association Between Enlarged Genital Hiatus and Composite Surgical Failure After Vaginal Hysterectomy With Uterosacral Ligament Suspension.

Importance: The impact of a persistently enlarged genital hiatus (GH) after vaginal hysterectomy with uterosacral ligament suspension on prolapse outcomes is currently unclear.

Objectives: This secondary analysis of the Study of Uterine Prolapse Procedures Randomized trial was conducted among participants who underwent vaginal hysterectomy with uterosacral ligament suspension. We hypothesized that women with a persistently enlarged GH size would have a higher proportion of prolapse recurrence.

Intraoperative Gentamicin Intravesical Instillation for Prevention of Urinary Tract Infection After Urogynecologic Surgery: A Randomized Controlled Trial.

Importance: Currently available evidence for efficacy of postoperative antibiotics to prevent postoperative urinary tract infection (UTI) conflicts. Oral antibiotics rely on patient adherence and can cause unwanted systemic effects. Gentamicin is a broad-spectrum antibiotic with rapid bactericidal activity and, when administered intravesically, has no systemic absorption through intact urothelium.

Long-term Urinary Outcomes After Transvaginal Uterovaginal Prolapse Repair With and Without Concomitant Midurethral Slings.

Importance: Many health care providers place concomitant midurethral slings during pelvic organ prolapse repair, yet growing evidence supports staged midurethral sling placement.

Objectives: The aim of this study was to compare urinary function after transvaginal uterovaginal prolapse repair with and without midurethral sling.

Study Design: Secondary analysis of the Study of Uterine Prolapse Procedures Randomized Trial (hysterectomy with uterosacral ligament suspension vs mesh hysteropexy).

Impact of Vaginal Estrogen on the Urobiome in Postmenopausal Women With Recurrent Urinary Tract Infection.

Objective: The aim of this study was to describe effects of vaginal estrogen (VE) on the urogenital microbiome in postmenopausal women with recurrent urinary tract infections (rUTIs).

Methods: This is a secondary analysis of 17 participants enrolled in a randomized controlled trial of VE versus placebo on urinary tract infection recurrence in postmenopausal women with rUTIs. Paired clean-catch urine samples were collected at baseline and after 6 months of VE and sequenced using 16S rRNA gene sequencing.

Pivotal Study of Leadless Tibial Nerve Stimulation with eCoin® for Urgency Urinary Incontinence: An Open-Label, Single Arm Trial.

Purpose: A novel leadless tibial nerve stimulator provides a primary battery-powered, coin-sized, minimally invasive option to deliver automatic low-duty cycle stimulation for overactive bladder syndrome therapy. A pivotal trial was conducted to evaluate the safety and efficacy of this investigational device, eCoin®, for treating refractory urgency urinary incontinence.

Materials And Methods: This was a prospective, open-label, single arm trial carried out at 15 U.

Persistence in Percutaneous Tibial Nerve Stimulation Treatment for Overactive Bladder Syndrome is Best Predicted by Patient Global Impression of Improvement Rather Than Symptom-Specific Improvement.

Objectives: To evaluate whether progression to maintenance percutaneous tibial nerve stimulation (PTNS) was related to perceived global impression of improvement (PGII) rather than symptom-specific improvement in patient with overactive bladder (OAB). We hypothesize that PGII will predict continuation of PTNS long-term.

Methods: This prospective observational study included 90 patients with OAB that initiated PTNS.

Do Women Who Self-report More Exercise Have Increased Rates of Symptomatic Stress Urinary Incontinence After Midurethral Slings?

Objectives: There is a paucity of data on postoperative exercise and how it relates to surgical failure, specifically after midurethral sling (MUS) surgery. We aimed to assess if women with higher self-reported activity levels as measured by strenuous exercise are more likely to experience stress urinary incontinence (SUI) symptoms after MUS than women with lower self-reported activity.

Methods: This is a secondary analysis of Operations and Pelvic Muscle Training in the Management of Apical Support Loss: the OPTIMAL Trial, a randomized trial comparing sacrospinous ligament suspension versus uterosacral ligament suspension, both with concomitant retropubic MUS.

Androgen Receptor Modulation Optimized for Response-Splice Variant: A Phase 3, Randomized Trial of Galeterone Versus Enzalutamide in Androgen Receptor Splice Variant-7-expressing Metastatic Castration-resistant Prostate Cancer.

Background: Detection of androgen receptor (AR) splice variant-7 (AR-V7) messenger RNA (mRNA) in circulating tumor cells (CTCs) is associated with a suboptimal response to abiraterone and enzalutamide in metastatic castration-resistant prostate cancer (mCRPC). Galeterone inhibits CYP17 and AR, and induces AR protein degradation. We hypothesized that galeterone would be clinically superior to enzalutamide in AR-V7-positive (AR-V7+) mCRPC.

Vaginal Estrogen for the Prevention of Recurrent Urinary Tract Infection in Postmenopausal Women: A Randomized Clinical Trial.

Objectives: We aimed to compare the efficacy of 2 commonly used contemporary vaginal estrogen administrations versus placebo for the prevention of urinary tract infection (UTI) in postmenopausal women with a clinical diagnosis of recurrent UTI (rUTI).

Methods: This was an investigator-initiated, multicenter, single-blind, randomized, placebo-controlled trial of vaginal estrogen (delivered via ring or cream) compared with placebo. Postmenopausal women with documented rUTI were randomized to receive either vaginal estrogen (via ring or cream) or placebo cream in a 1:1:1 fashion.

Teaching Vaginal Hysterectomy via Simulation: Creation and Validation of the Objective Skills Assessment Tool for Simulated Vaginal Hysterectomy on a Task Trainer and Performance Among Different Levels of Trainees.

Objectives: The use of simulation-based education to train surgeons is widely accepted. Although many authors describe the use of an Objective Skills Assessment Test (OSAT) to assess performance of various surgical procedures, there is a paucity of research on use of this modality to evaluate vaginal surgery skills. We created a vaginal hysterectomy procedure-specific checklist (PSC) to complete the OSAT (which is composed of a PSC and a global rating scale [GRS]).

Urologic and Gynecologic Sources of Pelvic Pain.

Gynecologic and urologic etiologies are the sources of pelvic pain for many individuals. This article aims to provide a comprehensive review of the various genitourinary sources of pelvic pain. It is important to recognize that although these disorders predominantly affect women, there are various conditions that affect both men and women, and these should be considered in the differential diagnosis of patients presenting with pelvic pain.

Androgen Receptor Modulation Optimized for Response (ARMOR) Phase I and II Studies: Galeterone for the Treatment of Castration-Resistant Prostate Cancer.

Purpose: Galeterone is a selective, multitargeted agent that inhibits CYP17, antagonizes the androgen receptor (AR), and reduces AR expression in prostate cancer cells by causing an increase in AR protein degradation. These open-label phase I and II studies [Androgen Receptor Modulation Optimized for Response-1 (ARMOR1) and ARMOR2 part 1] evaluated the efficacy and safety of galeterone in patients with treatment-naive nonmetastatic or metastatic castration-resistant prostate cancer (CRPC) and established a dose for further study.

Experimental Design: In ARMOR1, 49 patients received increasing doses (650-2,600 mg) of galeterone in capsule formulation; 28 patients in ARMOR2 part 1 received increasing doses (1,700-3,400 mg) of galeterone in tablet formulation for 12 weeks.

A randomized trial of vaginal mesh attachment techniques for minimally invasive sacrocolpopexy.

Introduction And Hypothesis: We investigated the efficiency and efficacy of vaginal mesh attachment using interrupted, non-barbed, delayed absorbable sutures in comparison with a running, barbed, delayed absorbable suture during laparoscopic sacrocolpopexy (LSC) and robotic sacrocolpopexy (RSC).

Methods: Women undergoing LSC or RSC were recruited. Participants were randomized to at least six 0 PDS non-barbed interrupted sutures or at least six passes of a 1 PDS barbed suture (Quill™) on each anterior and posterior polypropylene mesh leaflet.

Repeat post-op voiding trials: an inconvenient correlate with success.

Aims: This study examined the association between the need for a repeat voiding trial after midurethral sling (MUS) surgery and 1-year success rates.

Methods: We conducted this secondary analysis of the participants in the Urinary Incontinence Treatment Network trial of midurethral sling (TOMUS) study which compared retropubic versus transobturator MUS. A standard voiding trial was attempted on all subjects.

Safety and tolerability of high-dosage coenzyme Q10 in Huntington's disease and healthy subjects.

Coenzyme Q10 (CoQ(10)), a potential neuroprotective compound, was previously investigated at a dosage of 600 mg/day in Huntington's disease (HD) patients and demonstrated a trend toward slowing disease progression. Higher CoQ(10) dosages may prove beneficial. We investigated the tolerability and blood levels associated with 1,200, 2,400, and 3,600 mg/day of CoQ(10) in HD and healthy subjects.

Analysis of factors that modify susceptibility and rate of progression in amyotrophic lateral sclerosis (ALS).

We conducted case-control and prospective longitudinal studies to examine risk factors and predictors of disease progression for ALS. Ninety-five subjects with ALS and 106 healthy control subjects were enrolled. All subjects completed a risk factor questionnaire at enrollment.

Tolerance of high-dose (3,000 mg/day) coenzyme Q10 in ALS.

An open-label dose-escalation trial was performed to assess the safety and tolerability of high doses of coenzyme Q10 (CoQ10) in ALS. CoQ10, a cofactor in mitochondrial electron transfer, may improve the mitochondrial dysfunction in ALS. In this study, CoQ10 was safe and well tolerated in 31 subjects treated with doses as high as 3,000 mg/day for 8 months.

Detection of serum reverse transcriptase activity in patients with ALS and unaffected blood relatives.

Background: Retroviral involvement in the etiology of sporadic ALS has been suspected for several years since the recognition that both murine and human retroviruses can cause motor neuron disease-like syndromes. In a pilot study, an increased prevalence of a retroviral marker (reverse transcriptase [RT] activity) was demonstrated in the serum of British patients with ALS. The current investigation was designed to confirm and extend these findings in a geographically distinct patient cohort under blinded testing conditions.

A phase I and pharmacologic study of the matrix metalloproteinase inhibitor CP-471,358 in patients with advanced solid tumors.

Background: Matrix metalloproteinases play a role in the process of tissue invasion and metastasis by degrading the extracellular matrix. Inhibitors of matrix metalloproteinases are therefore of interest as anticancer drugs. CP-471,358 is a matrix metalloproteinase inhibitor that in vitro demonstrates strong inhibition of matrix metalloproteinases 2 and 9.

A phase I open label study of the farnesyltransferase inhibitor CP-609,754 in patients with advanced malignant tumors.

Purpose: The purpose of this phase I clinical trial was to determine the maximum-tolerated dose and toxicity of CP-609,754 in patients with solid tumors refractory to standard therapies, to determine the cellular effects of CP-609,754 on its molecular target (farnesyltransferase), and to determine the recommended phase II dose (RP2D) of this agent.

Experimental Design: Consenting patients with adequate bone marrow, liver, and renal function were enrolled with an accelerated dose strategy with single-patient parallel cohorts in whom the drug was given orally either once or twice daily. Once a dose-limiting toxicity was encountered or two patients developed Common Toxicity Criteria > or = grade 2 toxicities, a modified Fibonacci sequence was initiated.

Creatine therapy provides neuroprotection after onset of clinical symptoms in Huntington's disease transgenic mice.

While there have been enormous strides in the understanding of Huntington's disease (HD) pathogenesis, treatment to slow or prevent disease progression remains elusive. We previously reported that dietary creatine supplementation significantly improves the clinical and neuropathological phenotype in transgenic HD mice lines starting at weaning, before clinical symptoms appear. We now report that creatine administration started after onset of clinical symptoms significantly extends survival in the R6/2 transgenic mouse model of HD.

Therapeutic effects of coenzyme Q10 and remacemide in transgenic mouse models of Huntington's disease.

There is substantial evidence that bioenergetic defects and excitotoxicity may play a role in the pathogenesis of Huntington's disease (HD). Potential therapeutic strategies for neurodegenerative diseases in which there is reduced energy metabolism and NMDA-mediated excitotoxicity are the administration of the mitochondrial cofactor coenzyme Q10 and the NMDA antagonist remacemide. We found that oral administration of either coenzyme Q10 or remacemide significantly extended survival and delayed the development of motor deficits, weight loss, cerebral atrophy, and neuronal intranuclear inclusions in the R6/2 transgenic mouse model of HD.