Incontinence pessaries: size, POPQ measures, and successful fitting

The aim of the study was to determine whether successful incontinence pessary fitting or pessary size can be predicted by specific POPQ measurements in women without advanced pelvic organ prolapse. In a multicenter study, women with stress urinary incontinence (SUI) and POPQ stage ≤2 were randomized to three treatment arms: (1) incontinence pessary, (2) behavioral therapy, or (3) both. This study evaluates incontinence pessary size, POPQ measures, and successful fitting in the 266 women assigned to treatment arms 1 and 3. Two hundred thirty-five women (92%) were successfully fitted with an incontinence ring (n = 122) or dish (n = 113). Hysterectomy, genital hiatus (GH), and GH/total vaginal length (TVL) ratios did not predict unsuccessful fitting (p > 0.05). However, mean TVL was greater in women successfully fitted (9.6 vs. 8.8 cm, p < 0.01). Final pessary diameter was not predicted by TVL, point D, or point C (p > 0.05). The vast majority of women with SUI can be successfully fitted with an incontinence pessary, but specific POPQ measures were not helpful in determining incontinence pessary size

Does urethral competence affect urodynamic voiding parameters in women with prolapse?

Aims To (1) compare voiding parameters and (2) correlate symptoms and urodynamic findings in women with pelvic organ prolapse (POP) and varying degrees of urethral competence. Methods We compared three groups of women with stages II–IV POP. Groups 1 and 2 were symptomatically stress continent women participating in the Colpopexy and Urinary Reduction Efforts (CARE) trial; during prolapse reduction before sacrocolpopexy, Group 1 (n = 67) did not have and Group 2 (n = 84) had urodynamic stress incontinence (USI) during prolapse reduction. Group 3 participants (n = 74), recruited specifically for this study, had stress urinary incontinence (SUI) symptoms and planned sacrocolpopexy. Participants completed standardized uroflowmetry, pressure voiding studies, and validated symptom questionnaires. Results Subjects' median age was 61 years, median parity 3 and 87% had stage III or IV POP. Fourteen percent of women in Group 3 demonstrated USI without, and 70% with, prolapse reduction. Women in Groups 2 and 3 had more detrusor overactivity (DO) than Group 1 (17 and 24% vs. 6%, P  = 0.02) and detrusor overactivity incontinence (DOI) (15 and 8% vs. 0%, P  = 0.004). Based on the Blaivis–Groutz nomogram, 60% of all women were obstructed. Post-void residual volume (PVR), peak flow rate, detrusor pressure at peak flow, voiding mechanisms, voiding patterns, obstruction and urinary retention did not differ among groups. Women in Group 3 had higher irritative and obstructive symptom scores than Group 1 or 2; neither score differed by presence of DO nor obstruction, respectively. Conclusion Women with POP have significant rates of urodynamic obstruction and retention, independent of their continence status. Symptoms of obstruction and retention correlate poorly with urodynamic findings. Neurourol. Urodynam. 26:1030–1035, 2007. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/57365/1/20436_ftp.pd

Risk Factors for Fecal and Urinary Incontinence After Childbirth: The Childbirth and Pelvic Symptoms Study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73402/1/j.1572-0241.2007.01364.x.pd

Two-Year Outcomes After Sacrocolpopexy With and Without Burch to Prevent Stress Urinary Incontinence

To report anatomic and functional outcomes 2 years after sacrocolpopexy in stress-continent women with or without prophylactic Burch colposuspension

Refractory Idiopathic Urge Urinary Incontinence and Botulinum A Injection

We compared 200 U intradetrusor botulinum toxin A vs placebo in women with refractory idiopathic urge incontinence

Enhancing Participation of Older Women in Surgical Trials

Older participants are often excluded from clinical trials, precluding a representative sample

Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence

Intelligence is highly heritable(1) and a major determinant of human health and well-being(2). Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.Peer reviewe

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries