Remote assessment of the Penn computerised neurocognitive battery in individuals with 22q11.2 deletion syndrome.

BACKGROUND: Neurocognitive functioning is an integral phenotype of 22q11.2 deletion syndrome relating to severity of psychopathology and outcomes. A neurocognitive battery that could be administered remotely to assess multiple cognitive domains would be especially beneficial to research on rare genetic variants, where in-person assessment can be unavailable or burdensome. The current study compares in-person and remote assessments of the Penn computerised neurocognitive battery (CNB). METHODS: Participants (mean age = 17.82, SD = 6.94 years; 48% female) completed the CNB either in-person at a laboratory (n = 222) or remotely (n = 162). RESULTS: Results show that accuracy of CNB performance was equivalent across the two testing locations, while slight differences in speed were detected in 3 of the 11 tasks. CONCLUSIONS: These findings suggest that the CNB can be used in remote settings to assess multiple neurocognitive domains.

Treatment variation in stent choice in patients with stable or unstable coronary artery disease.

AIM: Variations in treatment are the result of differences in demographic and clinical factors (e.g. anatomy), but physician and hospital factors may also contribute to treatment variation. The choice of treatment is considered important since it could lead to differences in long-term outcomes. This study explores the associations with stent choice: i.e. drug-eluting stent (DES) versus bare-metal stents (BMS) for Dutch patients diagnosed with stable or unstable coronary artery disease (CAD). METHODS & RESULTS: Associations with treatment decisions were based on a prospective cohort of 692 patients with stable or unstable CAD. Of those patients, 442 patients were treated with BMS or DES. Multiple logistic regression analyses were performed to identify variables associated with stent choice. Bivariate analyses showed that NYHA class, number of diseased vessels, previous percutaneous coronary intervention, smoking, diabetes, and the treating hospital were associated with stent type. After correcting for other associations the treating hospital remained significantly associated with stent type in the stable CAD population. CONCLUSIONS: This study showed that several factors were associated with stent choice. While patients generally appear to receive the most optimal stent given their clinical characteristics, stent choice seems partially determined by the treating hospital, which may lead to differences in long-term outcomes.

Next-generation sequencing reveals novel rare fusion events with functional implication in prostate cancer.

Gene fusions, mainly between TMPRSS2 and ERG, are frequent early genomic rearrangements in prostate cancer (PCa). In order to discover novel genomic fusion events, we applied whole-genome paired-end sequencing to identify structural alterations present in a primary PCa patient (G089) and in a PCa cell line (PC346C). Overall, we identified over 3800 genomic rearrangements in each of the two samples as compared with the reference genome. Correcting these structural variations for polymorphisms using whole-genome sequences of 46 normal samples, the numbers of cancer-related rearrangements were 674 and 387 for G089 and PC346C, respectively. From these, 192 in G089 and 106 in PC346C affected gene structures. Exclusion of small intronic deletions left 33 intergenic breaks in G089 and 14 in PC346C. Out of these, 12 and 9 reassembled genes with the same orientation, capable of generating a feasible fusion transcript. Using PCR we validated all the reliable predicted gene fusions. Two gene fusions were in-frame: MPP5-FAM71D in PC346C and ARHGEF3-C8ORF38 in G089. Downregulation of FAM71D and MPP5-FAM71D transcripts in PC346C cells decreased proliferation; however, no effect was observed in the RWPE-1-immortalized normal prostate epithelial cells. Together, our data showed that gene rearrangements frequently occur in PCa genomes but result in a limited number of fusion transcripts. Most of these fusion transcripts do not encode in-frame fusion proteins. The unique in-frame MPP5-FAM71D fusion product is important for proliferation of PC346C cells.

The effect of vaginal dissection on the pudendal nerve.

OBJECTIVE: To determine the effect of vaginal dissection on the pudendal nerve. METHODS: Pudendal and perineal nerve terminal motor latencies were measured before and at least 6 weeks after either abdominal or vaginal surgery for genital tract prolapse with or without urinary and fecal incontinence. Forty-eight women were studied prospectively in a randomized, blinded fashion. RESULTS: All women in this study had pelvic floor prolapse, and their mean preoperative pudendal and perineal nerve terminal motor latencies were prolonged compared to previously established normal values. The 27 women undergoing vaginal dissection demonstrated significant mean increases in pudendal nerve terminal motor latency (0.63 milliseconds, 95% confidence interval [CI] 0.33-0.93; P = .001) and perineal nerve terminal motor latency (1.33 milliseconds, 95% CI 0.80-1.86; P = .0001). In the 21 who had abdominal operations without vaginal dissection, essentially no mean change was noted. Clinically significant increases (more than 2 standard deviations) in pudendal or perineal nerve terminal motor latency occurred in 20 women (74%) in the vaginal dissection group and in seven women (33%) in the abdominally operated group. The odds ratio of producing such neuropathy by vaginal dissection compared to operating abdominally without vaginal dissection was 5.78 (95% CI 1.6-20). CONCLUSIONS: All women had abnormal preoperative pudendal nerve function, supporting previous reports linking pudendal neuropathy with pelvic floor prolapse. Pelvic floor surgery involving vaginal dissection produces neuropathy of the pudendal nerve as measured by terminal motor latency.

Evaluation of a minimal-incision pubovaginal suspension as an adjunct to other pelvic-floor surgery.

In September 1987, Gittes and Loughlin first described a minimal-incision pubovaginal suspension as a modification of the Pereyra needle suspension urethropexy. Thirty-four women who underwent the minimal-incision urethropexy procedure were studied for up to 13 months postoperatively. Although 21 patients also had the anterior vaginal wall opened to perform concomitant pelvic-floor surgery, the principles of minimal suprapubic incision, full-thickness vaginal sutures, and no dissection of endopelvic fascia were followed strictly in all 34 cases. With a mean follow-up of 9.5 months, the objective cure rate was 91% and subjectively, 97% of the patients were either cured or improved. This technically simpler procedure is effective for treating genuine stress urinary incontinence in women who also require surgical repair of other pelvic-floor defects.

Intravaginal maximal electrical stimulation in the treatment of urinary incontinence.

Urinary incontinence imposes a large economic burden, estimated at $10 billion per year. As the cost of health care continues to rise, conservative therapeutic measures are becoming more attractive. Anecdotal reports suggest that electrical stimulation may be up to 87% effective in the treatment of urinary incontinence. Investigators use different stimulation devices and protocols and make a comparison of results difficult. The true efficacy of electrical stimulation for the treatment of urinary incontinence is unknown since there have been no controlled clinical trials. Within our referral-based urogynecology practice, we employ intermittent, intravaginal maximal electrical stimulation in conjunction with bladder drills and pelvic floor exercises. Over a one-year period we treated 76 women with urinary incontinence: 19 with stress incontinence (SUI), 30 with detrusor instability (DI) and 27 with mixed incontinence (MI). After six weeks, our overall objective improvement rate was 76%; 89% of patients with SUI, 73% with DI and 70% with MI met the criteria for improvement. Long-term follow-up averaged 6 months, with a range of 2-12. Of patients who showed an initial objective improvement, 87% maintained that improvement. Intravaginal electrical stimulation may be effective therapy for urinary incontinence. Controlled clinical trials are needed to determine its efficacy and standardize stimulation protocols before its widespread use.

Vaginal versus abdominal reconstructive surgery for the treatment of pelvic support defects: a prospective randomized study with long-term outcome evaluation.

OBJECTIVES: Our purpose was to determine whether a vaginal or abdominal approach is more effective in correcting uterovaginal prolapse. STUDY DESIGN: Eighty-eight women with cervical prolapse to or beyond the hymen or with vaginal vault inversion > 50% of its length and anterior vaginal wall descent to or beyond the hymen were randomized to a vaginal versus abdominal surgical approach. Forty-eight women underwent a vaginal approach with bilateral sacrospinous vault suspension and paravaginal repair, and 40 women underwent an abdominal approach with colposacral suspension and paravaginal repair. Ancillary procedures were performed as indicated. Detailed pelvic examination was performed postoperatively by the nonsurgeon coauthor yearly up to 5 years. The women were examined while standing during maximum strain. Surgery was classified as optimally effective if the woman remained asymptomatic, the vaginal apex was supported above the levator plate, and no protrusion of any vaginal tissue beyond the hymen occurred. Surgical effectiveness was considered unsatisfactory if the woman was symptomatic, the apex descended > 50% of its length, or the vaginal wall protruded beyond the hymen. RESULTS: Eighty women (vaginal 42, abdominal 38) were available for evaluation at 1 to 5.5 years (mean 2.5 years). The groups were similar in age, weight, parity, and estrogen status, and 56% had undergone prior pelvic surgery. There was no significant difference between the groups in morbidity, complications, hemoglobin change, dyspareunia, pain, or hospital stay. The vaginal group had longer catheter use, more urinary tract infections, more incontinence, decreased operative time, and lower hospital charge. Surgical effectiveness was optimal in 29% of the vaginal group and 58% of the abdominal group and was unsatisfactory leading to reoperation in 33% of the vaginal group and 16% of the abdominal group. The reoperations included procedures for recurrent incontinence in 12% of the vaginal and 2% of the abdominal groups. The relative risk of optimal effectiveness by the abdominal route is 2.03 (95% confidence interval 1.22 to 9.83), and the relative risk of unsatisfactory outcome using the vaginal route is 2.11 (95% confidence interval 0.90 to 4.94). CONCLUSIONS: Reconstructive pelvic surgery for correction of significant pelvic support defects was more effective with an abdominal approach.

Urethral sphincter needle electromyography in women: comparison of periurethral and transvaginal approaches.

Needle electromyography (EMG) of the striated urethral sphincter is the only technique that permits detection of individual motor unit action potentials (MUAPs) and is a valuable diagnostic tool in the evaluation of women with urinary incontinence and voiding disorders. The purpose of this study was to compare two methods of urethral needle EMG with respect to the number of MUAPs identified, the amount of patient discomfort, and the duration of the examination. Twenty consecutive women referred for electrodiagnostic testing to evaluate symptoms of urinary incontinence and/or voiding dysfunction underwent both methods of the needle examination in a prospective randomized cross-over study design with each patient acting as her own control. A full cross-over analysis was conducted to detect period and sequence effects using analysis of variance with a power of 0.85 and a significance level of P < 0.05. Twice as many MUAPs were identified using the periurethral approach (8.8 versus 3.9) with a mean difference of 5.0 (P=0.0008). There was a non-significant trend to greater patient discomfort with the periurethral approach; however, the discomfort was generally rated as mild to moderate. The length of time required to count all identifiable MUAPs did not vary significantly between the two methods. We conclude that the periurethral approach is superior to the transvaginal approach with respect to the quantity of electrodiagnostic information obtained and propose that this method be standardized to characterize more accurately the neurogenic component of urinary incontinence and voiding dysfunction for future electrodiagnostic studies.

Relationship between surgically induced neuropathy and outcome of pelvic organ prolapse surgery.

The aim of the study was to determine whether surgically induced perineal neuropathy relates to the outcome of surgery for the correction of pelvic organ prolapse. Perineal nerve terminal motor latencies (PeNTML) were obtained in 31 women prior to and following transvaginal surgery for the correction of pelvic organ prolapse consisting of bilateral sacrospinous ligament vault suspension and bilateral paravaginal cystocele repair. Mean follow-up was 32 months (range 12-60). Surgical outcome was defined as optimal (asymptomatic, with the apex of the vagina above the levator plate with no tissue protruding beyond the hymen in the upright position with maximum Valsalva), or suboptimal (apical descent of > 50%, or any vaginal wall protrusion beyond the hymen in the upright position with maximum Valsalva). Surgically induced neuropathy was defined as an increase of 0.6 ms or more in the averaged right and left PeNTML measurements following the surgery. All women had preoperative symptomatic prolapse and the mean preoperative PeNTML was prolonged compared to established normals. Using strict definitions, 11 women had optimal outcome and 20 had suboptimal outcome. The outcome groups were similar with respect to age, weight, parity, degree of preoperative prolapse and preoperative perineal neuropathy. Eleven women had surgically induced perineal neuropathy. This was associated with suboptimal outcome compared to optimal outcome (P = 0.03). The relative risk of suboptimal outcome with surgically induced neuropathy was 1.82 (95% CI 1.13-2.93). It was concluded that a relationship exists between the outcome of organ prolapse surgery and surgically induced perineal neuropathy as measured by PeNTML. Such neuropathy may play a role in failed pelvic reconstructive surgery.