Construction and validation of the chronic acquired polyneuropathy patient-reported index (CAP-PRI): A disease-specific, health-related quality-of-life instrument.

INTRODUCTION: Generic health-related quality-of-life (HRQOL) patient-reported outcome measures have been used in patients with chronic immune-mediated polyneuropathies. We have created a disease-specific HRQOL instrument. METHODS: The chronic acquired polyneuropathy patient-reported index (CAP-PRI) was developed and validated in multiple steps. Items were initially generated through patient and specialist input. The performance of the preliminary 20 items was analyzed via a prospective, 5-center study involving chronic immune-mediated polyneuropathy patients. RESULTS: Data analysis suggested modification to a 15-item scale with 3 response categories rather than 5. The final CAP-PRI was validated in another prospective, 5-center study. The CAP-PRI appeared to be a unidimensional outcome measure that fit the Rasch model in our multicenter cohort. It correlated appropriately with outcome measures commonly used in this patient population. CONCLUSIONS: The CAP-PRI is a simple disease-specific HRQOL measure that appears to be useful for clinical care and possibly also for clinical trials. Muscle Nerve 54: 9-17, 2016.

Genome-wide pharmacogenomic analysis of the response to interferon beta therapy in multiple sclerosis.

OBJECTIVE: To identify promising candidate genes linked to interindividual differences in the efficacy of interferon beta therapy. Recombinant interferon beta therapy is widely used to reduce disease activity in multiple sclerosis (MS). However, up to 50% of patients continue to have relapses and worsening disability despite therapy. DESIGN: We used a genome-wide pharmacogenomic approach to identify single-nucleotide polymorphism (SNP) allelic differences associated with interferon beta therapy response. SETTING: Four collaborating centers in the Mediterranean Basin. Data Coordination Center at the University of California, San Francisco. PATIENTS: A cohort of 206 patients with relapsing-remitting MS followed up prospectively for 2 years after initiation of treatment. INTERVENTION: DNA was pooled and hybridized to Affymetrix 100K GeneChips. Pooling schemes were designed to minimize confounding batch effects and increase confidence by technical replication. MAIN OUTCOME MEASURES: Single-nucleotide polymorphism detection. Comparison of allelic frequencies between good responders and nonresponders to interferon beta therapy. RESULTS: A multianalytical approach detected significant associations between several SNPs and treatment response, which were validated by individual DNA genotyping on an independent platform. After the validation stage was complete, 81 additional individuals were added to the analysis to increase power. We found that responders and nonresponders had significantly different genotype frequencies for SNPs located in many genes, including glypican 5, collagen type XXV alpha1, hyaluronan proteoglycan link protein, calpastatin, and neuronal PAS domain protein 3. CONCLUSIONS: The reported results address the question of genetic heterogeneity in MS and the response to immunotherapy by analysis of the correlation between different genotypes and clinical response to interferon beta therapy. Many of the detected differences between responders and nonresponders were genes associated with ion channels and signal transduction pathways. The study also suggests that genetic variants in heparan sulfate proteoglycan genes may be of clinical interest in MS as predictors of the response to therapy. In addition to new insights into the mechanistic biology of interferon beta, these results help define the molecular basis of interferon beta therapy response heterogeneity.

A meta-analysis of surgical practice patterns in the endoscopic management of ureteroceles.

PURPOSE: We examined the contribution of patient features on reoperation after transurethral incision or puncture in children with ureteroceles. MATERIALS AND METHODS: A systematic review was accomplished using Medline and article bibliographies to obtain articles related to endoscopic management of ureteroceles in English, Spanish, Italian, French and Japanese. Exposures of interest were ureterocele position and anatomy, and preoperative reflux. The outcome was secondary operation. Meta-analysis was done using Mantel-Haenszel calculations. RESULTS: Meta-analysis of 10 studies demonstrated that ectopic ureteroceles are associated with significantly greater reoperation rates than intravesical ureteroceles in patients undergoing ureterocele incision. This remains true with longer followup and systematic ureterocele incision/puncture, in neonates and in patients with single and duplex collecting systems. In addition, a meta-analysis of 3 studies showed that patients with duplex system ureteroceles are more likely to require subsequent operation. A third meta-analysis of 7 studies showed that preoperative reflux increases the risk of reoperation after ureterocele incision. More than 1 risk factor did not appear to increase the risk of secondary operation. CONCLUSIONS: To our knowledge this is the first systematic review of endoscopic ureterocele management. It suggests that ectopic ureterocele location, duplex renal systems and preoperative reflux are proxies for trigonal anatomical distortion, rather than independent risk factors for a secondary operation after incision. Findings reinforce the importance of considering these variables when making management decision in children with ureteroceles.

Lower urinary tract reconstruction for duplicated renal units with ureterocele. Is excision of the ureterocele with reconstruction of the bladder base necessary?

PURPOSE: Current practice in reconstruction of the lower urinary tract for duplicated renal systems with an associated ureterocele is excision of the ureterocele with reconstruction of the bladder and a common sheath ureteroneocystostomy. For a nonfunctioning upper pole treatment is partial nephroureterectomy. We postulate that lower urinary tract reconstruction can be performed successfully through an extravesical approach without excision of the ureterocele or reconstruction of the bladder base. We present our experience with that approach. MATERIALS AND METHODS: Between 1996 and 2001, 60 patients presented with the diagnosis of ureterocele and obstruction of the upper pole ureter. Partial nephrectomy was performed in 12 cases of which 4 had reflux to the lower pole moiety. Upper pole only dismembered ureteroneocystostomy was performed in 7 of 15 cases reconstructed using the extravesical approach. RESULTS: Average postoperative stay was 3.7 days. The Foley catheter was removed within 24 to 48 hours. Postoperative ultrasound showed decompression of the obstructed system and the ureterocele. Reflux was corrected in all patients. Flow rate with measurement of post-void residual 6 weeks postoperatively in toilet trained children showed complete bladder emptying. CONCLUSIONS: Lower urinary tract reconstruction for duplicated renal systems with obstruction of the upper pole can be accomplished safely with decreased morbidity through the extravesical approach without excision of the ureterocele or reconstruction of the bladder base. Moreover, in instances when there is no reflux to the lower pole moiety, upper pole only extravesical ureteroneocystostomy can be performed.