Characteristics Associated with Treatment Response and Satisfaction in Women Undergoing OnabotulinumtoxinA and Sacral Neuromodulation for Refractory Urgency Urinary Incontinence.

PURPOSE: We sought to identify clinical and demographic characteristics associated with treatment response and satisfaction in women undergoing onabotulinumtoxinA and sacral neuromodulation therapies. MATERIALS AND METHODS: We analyzed data from the ROSETTA (Refractory Overactive Bladder: Sacral NEuromodulation versus BoTulinum Toxin Assessment) trial. Baseline participant characteristics and clinical variables were associated with 2 definitions of treatment response, including 1) a reduction in mean daily urgency incontinence episodes during 6 months and 2) a 50% or greater decrease in urgency incontinence episodes across 6 months. The OAB-S (Overactive Bladder-Satisfaction) questionnaire was used to assess satisfaction. RESULTS: A greater reduction in mean daily urgency incontinence episodes was associated with higher HUI-3 (Health Utility Index-3) scores in the onabotulinumtoxinA group and higher baseline incontinence episodes (each p <0.001) in the 2 groups. Increased age was associated with a lesser decrease in incontinence episodes in the 2 groups (p <0.001). Increasing body mass index (adjusted OR 0.82/5 points, 95% CI 0.70-0.96) was associated with reduced achievement of a 50% or greater decrease in incontinence episodes after each treatment. Greater age (adjusted OR 0.44/10 years, 95% CI 0.30-0.65) and a higher functional comorbidity index (adjusted OR 0.84/1 point, 95% CI 0.71-0.99) were associated with reduced achievement of a 50% or greater decrease in urgency incontinence episodes in the onabotulinumtoxinA group only (p <0.001 and 0.041, respectively). In the onabotulinumtoxinA group increased satisfaction was noted with higher HUI-3 score (p = 0.002) but there was less satisfaction with higher age (p = 0.001). CONCLUSIONS: Older women with multiple comorbidities, and decreased functional and health related quality of life had decreased treatment response and satisfaction with onabotulinumtoxinA compared to sacral neuromodulation for refractory urgency incontinence.

Contribution of Clostridium difficile infection to the development of lower gastrointestinal adverse events during autologous stem cell transplantation.

BACKGROUND: Lower gastrointestinal (GI) adverse events (LGAE) are common afflictions of patients undergoing stem cell transplantation (SCT). Unfortunately, the pathophysiology remains poorly characterized. Emerging data suggest a prominent role of intestinal microbiota; however, contributions of pathogenic gut microbiota such as Clostridium difficile are not well defined. We performed a genome-wide association study (GWAS) to investigate clinical and genetic factors associated with development of LGAE. METHODS: A total of 972 patients undergoing autologous SCT were graded for LGAE based on Common Terminology Criteria for Adverse Events (v 4.0). Germline DNA material was obtained from leukapharesis products and genotyped using Illumina(®) Whole Genome Genotyping Infinium chemistry and HumanOmni1-Quad Bead chips containing over 1.1 million single nucleotide polymorphisms (SNPs) (Illumina, San Diego, California, USA). Statistical models incorporating clinical factors, genetic factors, and a combination of clinical plus genetic factors were utilized to compare patients who developed severe LGAE (grade 2 or above) and others. RESULTS: Among 972 patients, 459 (47.2%) developed severe LGAE. Baseline hemoglobin and hematocrit, estimated glomerular filtration rate, ß2-microglobulin, protocol type, and C. difficile infection (CDI) were associated with severe LGAE on univariate analysis, Genomic comparisons between groups did not reveal any SNPs associated with severe LGAE and neither did incorporation of genetic factors into the clinical model. In addition, 11 candidate SNPs associated with upper GI mucositis were evaluated, alongside clinical factors in a multivariate model. Only CDI was found to be associated with severe LGAE in all models. CONCLUSION: CDI is a prominent factor in the development of LGAE in patients undergoing autologous SCT.

The effect of detomidine and its antagonism with tolazoline on stress-related hormones, metabolites, physiologic responses, and behavior in awake ponies.

Six ponies were used to investigate the effect of tolazoline antagonism of detomidine on physiological responses, behavior, epinephrine, norepinephrine, cortisol, glucose, and free fatty acids in awake ponies. Each pony had a catheter inserted into a jugular vein 1 hour before beginning the study. Awake ponies were administered detomidine (0.04 mg/kg intravenously [i.v.]) followed 20 minutes later by either tolazoline (4.0 mg/kg i.v.) or saline. Blood samples were drawn from the catheter 5 minutes before detomidine administration (baseline), 5 minutes after detomidine administration, 20 minutes before detomidine administration which was immediately before the administration of tolazoline or saline (time [T] = 0), and at 5, 30, and 60 minutes after injections of tolazoline or saline (T = 5, 30, and 60 minutes, respectively). Compared with heart rate at T = 0, tolazoline antagonism increased heart rate 45% at 5 minutes. There was no difference in heart rate between treatments at 30 minutes. Blood pressure remained stable after tolazoline, while it decreased over time after saline. Compared with concentrations at T = 0, tolazoline antagonism of detomidine in awake ponies resulted in a 55% increase in cortisol at 30 minutes and a 52% increase in glucose at 5 minutes. The change in free fatty acids was different for tolazoline and saline over time. Free fatty acids decreased after detomidine administration. Free fatty acids did not change after saline administration. After tolazoline administration, free fatty acids increased transiently. Tolazoline tended to decrease sedation and analgesia at 15 and 60 minutes postantagonism. Antagonism of detomidine-induced physiological and behavioral effects with tolazoline in awake ponies that were not experiencing pain appears to precipitate a stress response as measured by cortisol, glucose, and free fatty acids. If antagonism of an alpha-agonist is contemplated, the potential effect on hormones and metabolites should be considered.

Computer technique for monitoring time dependent changes from sequential CT images.

The sequential computed tomography (CT) images used in this manuscript are electrocardiogram-gated images of the same cross section of the heart (10 in this study) depicting one cardiac cycle from end-diastole to the next end-diastole. Each of these 10 reconstructions corresponds to 10% intervals extending from one R wave to the next R wave. When each image of the series of 10 images is assigned a consecutive table position, using the program for sagittal reconstructions a chronogram along any line through the X-Y plane of the left ventricular (LV) wall can be produced. The chronograms display changes in wall thickness and wall motion in relation to time throughout the cardiac cycle at a preselected site in the LV and can be used to demonstrate the LV myocardial response to perturbations. This technique adds the dimension of time to spatial information in the CT images and can be used to monitor cardiac physiology in a quantitative fashion.