Coexisting depressive symptoms do not limit the benefits of chronic neuromodulation: A study of over 200 patients

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142918/1/nau23356_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142918/2/nau23356.pd

Novel Application of Statistical Methods to Identify New Urinary Incontinence Risk Factors

Longitudinal data for studying urinary incontinence (UI) risk factors are rare. Data from one study, the hallmark Medical, Epidemiological, and Social Aspects of Aging (MESA), have been analyzed in the past; however, repeated measures analyses that are crucial for analyzing longitudinal data have not been applied. We tested a novel application of statistical methods to identify UI risk factors in older women. MESA data were collected at baseline and yearly from a sample of 1955 men and women in the community. Only women responding to the 762 baseline and 559 follow-up questions at one year in each respective survey were examined. To test their utility in mining large data sets, and as a preliminary step to creating a predictive index for developing UI, logistic regression, generalized estimating equations (GEEs), and proportional hazard regression (PHREG) methods were used on the existing MESA data. The GEE and PHREG combination identified 15 significant risk factors associated with developing UI out of which six of them, namely, urinary frequency, urgency, any urine loss, urine loss after emptying, subject's anticipation, and doctor's proactivity, are found most highly significant by both methods. These six factors are potential candidates for constructing a future UI predictive index

Novel Application of Statistical Methods to Identify New Urinary Incontinence Risk Factors

Longitudinal data for studying urinary incontinence (UI) risk factors are rare. Data from one study, the hallmark Medical, Epidemiological, and Social Aspects of Aging (MESA), have been analyzed in the past; however, repeated measures analyses that are crucial for analyzing longitudinal data have not been applied. We tested a novel application of statistical methods to identify UI risk factors in older women. MESA data were collected at baseline and yearly from a sample of 1955 men and women in the community. Only women responding to the 762 baseline and 559 follow-up questions at one year in each respective survey were examined. To test their utility in mining large data sets, and as a preliminary step to creating a predictive index for developing UI, logistic regression, generalized estimating equations (GEEs), and proportional hazard regression (PHREG) methods were used on the existing MESA data. The GEE and PHREG combination identified 15 significant risk factors associated with developing UI out of which six of them, namely, urinary frequency, urgency, any urine loss, urine loss after emptying, subject’s anticipation, and doctor’s proactivity, are found most highly significant by both methods. These six factors are potential candidates for constructing a future UI predictive index

Contemporary diagnosis and management of Fournier’s gangrene

Fournier’s gangrene, an obliterative endarteritis of the subcutaneous arteries resulting in gangrene of the overlying skin, is a rare but severe infective necrotizing fasciitis of the external genitalia. Mainly associated with men and those over the age of 50, Fournier’s gangrene has been shown to have a predilection for patients with diabetes as well as people who are long-term alcohol misusers. The nidus for the synergistic polymicrobial infection is usually located in the genitourinary tract, lower gastointestinal tract or skin. Early diagnosis remains imperative as rapid progression of the gangrene can lead to multiorgan failure and death. The diagnosis is often made clinically, although radiography can be helpful when the diagnosis or the extent of the disease is difficult to discern. The Laboratory Risk Indicator for Necrotizing Fasciitis score can be used to stratify patients into low, moderate or high risk and the Fournier’s Gangrene Severity Index (FGSI) can also be used to determine the severity and prognosis of Fournier’s gangrene. Mainstays of treatment include rapid and aggressive surgical debridement of necrotized tissue, hemodynamic support with urgent resuscitation with fluids, and broad-spectrum parental antibiotics. After initial radical debridement, open wounds are generally managed with sterile dressings and negative-pressure wound therapy. In cases of severe perineal involvement, colostomy has been used for fecal diversion or alternatively, the Flexi-Seal Fecal Management System can be utilized to prevent fecal contamination of the wound. After extensive debridement, many patients sustain significant defects of the skin and soft tissue, creating a need for reconstructive surgery for satisfactory functional and cosmetic results

US Pilot Study of Lumbar to Sacral Nerve Rerouting to Restore Voiding and Bowel Function in Spina Bifida: 3-Year Experience

Objective. To report our experience with creating a skin-central nervous system-bladder reflex arc with intradural lumbar to sacral motor root microanastomosis to restore bladder/bowel function in spina bifida patients. Methods. Urinary/bowel changes from baseline to three years were evaluated with questionnaires, voiding diaries, urodynamics (UDS), and renal function studies. Treatment response was defined as CIC ≤ once/day with stable renal function, voiding efficiency > 50%, and no worsening of motor function. Results. Of 13 subjects (9 female, median age 8 years), 3 voided small amounts at baseline, one voided 200 cc (voiding efficiency 32%), 4/13 reported normal bowels, and 2/13 were continent of stool. Postoperatively, all had transient lower extremity weakness; one developed permanent foot drop. Over three years, renal function remained stable and mean maximum cystometric capacity (MCC) increased (P=0.0135). In the 10 that returned at 3 years, 7 were treatment responders and 9 had discontinued antimuscarinics, but most still leaked urine. Only 2/8 with baseline neurogenic detrusor overactivity (NDO) still had NDO, all 3 with compliance <10 mL/cm H2O had normalized, 7/10 considered their bowels normal, 5/10 were continent of stool, and 8/10 would undergo the procedure again. Conclusion. Lumbar to sacral nerve rerouting can improve elimination in spina bifida patients. This trial is registered with ClinicalTrials.gov NCT00378664

Predictors of Incisional Hernia after Robotic Assisted Radical Prostatectomy

Introduction. To explore the long term incidence and predictors of incisional hernia in patients that had RARP. Methods. All patients who underwent RARP between 2003 and 2012 were mailed a survey reviewing hernia type, location, and repair. Results. Of 577 patients, 48 (8.3%) had a hernia at an incisional site (35 men had umbilical), diagnosed at (median) 1.2 years after RARP (mean follow-up of 5.05 years). No statistically significant differences were found in preoperative diabetes, smoking, pathological stage, age, intraoperative/postoperative complications, operative time, blood loss, BMI, and drain type between patients with and without incisional hernias. Incisional hernia patients had larger median prostate weight (45 versus 38 grams; P=0.001) and a higher proportion had prior laparoscopic cholecystectomy (12.5% (6/48) versus 4.6% (22/480); P=0.033). Overall, 4% (23/577) of patients underwent surgical repair of 24 incisional hernias, 22 umbilical and 2 other port site hernias. Conclusion. Incisional hernia is a known complication of RARP and may be associated with a larger prostate weight and history of prior laparoscopic cholecystectomy. There is concern about the underreporting of incisional hernia after RARP, as it is a complication often requiring surgical revision and is of significance for patient counseling before surgery

Screening Nylon‑3 Polymers, a New Class of Cationic Amphiphiles, for siRNA Delivery

Amphiphilic nucleic acid carriers have attracted strong interest. Three groups of nylon-3 copolymers (poly-β-peptides) possessing different cationic/hydrophobic content were evaluated as siRNA delivery agents in this study. Their ability to condense siRNA was determined in SYBR Gold assays. Their cytotoxicity was tested by MTT assays, their efficiency of delivering Alexa Fluor-488-labeled siRNA intracellularly in the presence and absence of uptake inhibitors was assessed by flow cytometry, and their transfection efficacies were studied by luciferase knockdown in a cell line stably expressing luciferase (H1299/Luc). Endosomal release was determined by confocal laser scanning microscopy and colocalization with lysotracker. All polymers efficiently condensed siRNA at nitrogen-to-phosphate (N/P) ratios of 5 or lower, as reflected in hydrodynamic diameters smaller than that at N/P 1. Although several formulations had negative zeta potentials at N/P 1, G2C and G2D polyplexes yielded >80% uptake in H1299/Luc cells, as determined by flow cytometry. Luciferase knockdown (20–65%) was observed after transfection with polyplexes made of the high molecular weight polymers that were the most hydrophobic. The ability of nylon-3 polymers to deliver siRNA intracellularly even at negative zeta potential implies that they mediate transport across cell membranes based on their amphiphilicity. The cellular uptake route was determined to strongly depend on the presence of cholesterol in the cell membrane. These polymers are, therefore, very promising for siRNA delivery at reduced surface charge and toxicity. Our study identified nylon-3 formulations at low N/P ratios for effective gene knockdown, indicating that nylon-3 polymers are a new, promising type of gene delivery agent