Evaluation of two commercial, rapid, ELISA kits testing for scrapie in retro-pharyngeal lymph nodes in sheep.

AIMS: To estimate the number of cases of scrapie that would occur in sheep of different prion protein (PrP) genotypes if scrapie was to become established in New Zealand, and to compare the performance of two commercially available, rapid ELISA kits using ovine retro-pharyngeal lymph nodes (RLN) from non-infected and infected sheep of different PrP genotypes. METHODS: Using published data on the distribution of PrP genotypes within the New Zealand sheep flock and the prevalence of cases of scrapie in these genotypes in the United Kingdom, the annual expected number of cases of scrapie per genotype was estimated, should scrapie become established in New Zealand, assuming a total population of 28 million sheep. A non-infected panel of RLN was collected from 737 sheep from New Zealand that had been culled, found in extremis or died. Brain stem samples were also collected from 131 of these sheep. A second panel of infected samples comprised 218 and 117 RLN from confirmed scrapie cases that had originated in Europe and the United States of America, respectively. All samples were screened using two commercial, rapid, transmissible spongiform encephalopathy ELISA kits: Bio-Rad TeSeE ELISA (ELISA-BR), and IDEXX HerdChek BSE-Scrapie AG Test (ELISA-ID). RESULTS: If scrapie became established in New Zealand, an estimated 596 cases would occur per year; of these 234 (39%) and 271 (46%) would be in sheep carrying ARQ/ARQ and ARQ/VRQ PrP genotypes, respectively. For the non-infected samples from New Zealand the diagnostic specificity of both ELISA kits was 100%. When considering all infected samples, the diagnostic sensitivity was 70.4 (95% CI=65.3-75.3)% for ELISA-BR and 91.6 (95% CI=88.2-94.4)% for ELISA-ID. For the ARQ/ARQ genotype (n=195), sensitivity was 66.2% for ELISA-BR and 90.8% for ELISA-ID, and for the ARQ/VRQ genotype (n=107), sensitivity was 81.3% for ELISA-BR and 98.1% for ELISA-ID. CONCLUSIONS: In this study, the ELISA-ID kit demonstrated a higher diagnostic sensitivity for detecting scrapie in samples of RLN from sheep carrying scrapie-susceptible PrP genotypes than the ELISA-BR kit at comparable diagnostic specificity. CLINICAL RELEVANCE: The diagnostic performance of the ELISA-ID kit using ovine RLN merits the consideration of including this assay in the national scrapie surveillance programme in New Zealand.

Flexible dosing with fesoterodine 4 and 8 mg: a systematic review of data from clinical trials.

AIMS: To systematically review dose-escalation data from flexible-dose studies of fesoterodine and summarise factors associated with dose-escalation decisions. METHODS: A PubMed search was conducted using the terms (fesoterodine AND flexible dose), with no limits. Articles were included if they contained fesoterodine dose-escalation data for efficacy or safety outcomes or factors associated with dose-escalation decisions. RESULTS: Of 13 articles identified by the search, 10 articles (six clinical studies) met inclusion criteria. In flexible-dose trials of fesoterodine, 51-63% of subjects initially receiving fesoterodine 4 mg opted for dose escalation to fesoterodine 8 mg. Escalators generally reported significantly more severe overactive bladder (OAB) symptoms, greater OAB symptom bother and worse health-related quality of life at baseline than non-escalators. Escalators demonstrated less treatment benefit with fesoterodine 4 mg than non-escalators. Non-escalators generally had a higher rate of dry mouth and constipation with fesoterodine 4 mg than escalators. The decision to escalate appeared to be determined by the efficacy/tolerability responses; fesoterodine escalators demonstrated a lower sensitivity (less efficacy and fewer adverse events) before their decision to escalate. By study end (8-11 weeks after escalation decision), the efficacy and tolerability profiles were similar in escalators and non-escalators. CONCLUSIONS: Data from flexible-dose studies provide strong evidence that fesoterodine provides treatment benefit to individual subjects with OAB because of its true dose-response effect. In clinical practice, it can be worthwhile to escalate to fesoterodine 8 mg in individual subjects who require additional efficacy benefit.

A healthy bladder: a consensus statement.

A panel of experts in urology, urogynecology, nursing, and behavioral therapy convened in 2010 to discuss the importance of a healthy bladder on overall health. They determined that a consensus statement was necessary to raise awareness among the general public, healthcare providers, payors, and policymakers, with the goals of minimizing the impact of poor bladder health and stimulating primary prevention of bladder conditions. In this statement, 'healthy' bladder function is described, as well as internal and external factors that influence bladder health. It is suggested that primary prevention strategies should be aimed at providing education regarding normal lower urinary tract structures and functioning to the public, including patients and healthcare providers. This education may promote the achievement of optimal bladder health by increasing healthy bladder habits and behaviors, awareness of risk factors, healthcare seeking, and clinician engagement and reducing stigma and other barriers to treatment. Promoting optimal bladder health may reduce the personal, societal and economic impact of bladder conditions, including anxiety and depression and costs associated with conditions or diseases and their treatment. While adopting healthy bladder habits and behaviors and behaviors may improve or maintain bladder health, it is important to recognize that certain symptoms may indicate the presence of conditions that require medical attention; many bladder conditions are treatable with a range of options for most bladder conditions. Lastly, the authors propose clinical directives based on persuasive and convergent research to improve and maintain bladder health. The authors hope that this statement will lead to promotion and achievement of optimal bladder health, which may improve overall health and help minimize the effects of bladder conditions on the public, healthcare professionals, educators, employers, and payors. The advisors are in consensus regarding the recommendations for improving and maintaining bladder health presented herein.

Salmonella serotypes isolated from pet chews in New Zealand.

AIMS: To survey the prevalence of Salmonella in imported and domestic pet chews for assessing their potential in introducing novel pathogenic and antimicrobial resistant Salmonella serotype clones into New Zealand, and as vehicles of salmonellosis in the domestic home environment. METHODS AND RESULTS: Three hundred samples, each of imported and domestic pet chews, were examined bacteriologically for the presence of Salmonella. Salmonella cells in the pre-enrichment culture were concentrated by using Dynabeads, and then selective enrichment and plating were performed by a method described in the Bacteriological and Analytical Manual, USFDA. Salmonella was isolated from 16 (5.3%) of the imported and 20 (6.7%) of the domestic pet chews, but the prevalences of Salmonella in imported and domestic products were not significantly different. All Salmonella isolates were serotyped and genotyped by pulsed-field gel electrophoresis and antimicrobial susceptibility determined by the Clinical and Laboratory Standards Institute disc diffusion methods. Salmonella Borreze has never been recorded earlier in New Zealand and was detected from Australian raw hide. Three isolates of Salmonella London were resistant to ampicillin and gentamicin, and two isolates of Salmonella Infantis were resistant to nalidixic acid, one of which was also resistant to streptomycin. CONCLUSIONS: Novel pathogenic and antimicrobial-resistant Salmonella are being introduced into New Zealand through the import of pet chews. This indicates that pet chews are a potential source of exposure to Salmonella in the domestic home environment. SIGNIFICANCE AND IMPACT OF THE STUDY: Contaminated pet chews are potential sources of Salmonella infection for domestic pets, and humans are at risk of exposure either directly by contact through handling or inadvertently by cross-contamination of food or food-contact surfaces in home environments.

A practical guide to the evaluation and treatment of male lower urinary tract symptoms in the primary care setting.

AIMS: Lower urinary tract symptoms (LUTS) are common in both men and women, and are among the most prevalent patient complaints heard by primary care physicians (PCPs). This article aims to provide PCPs with a logical algorithm for the assessment and initiation of treatment for LUTS in the male patient. RESULTS: Management of LUTS involves a focused history and physical, as well as the assessment of bother. In patients for whom treatment is warranted, a series of decisions regarding therapy should be considered. Male patients commonly suffer from storage and/or voiding symptoms. Treatment of male LUTS is commonly begun with agents that are aimed at remedying the outlet symptoms of benign prostatic hyperplasia (BPH). When this intervention is ineffective or when refractory symptoms persist, consideration should be given to treating the storage symptoms characteristic of overactive bladder (OAB). DISCUSSION: This article is intended to provide the PCP with a logical guide to the treatment of male LUTS. Benign prostatic hyperplasia and OAB predominate among the causes of these symptoms, and the PCP should be comfortable treating each. Recent data detailing the safety of the use of these treatments in the male patient are reviewed and incorporated into the algorithm. CONCLUSION: Primary care physicians are in a unique position to successfully identify and treat male patients with LUTS. With this paper, they now have a tool to approach treatment logically and practically.

The role of neuromodulation in the management of urinary urge incontinence.

OBJECTIVE: To examine the benefit-risk profile of neuromodulation in treating refractory urinary urge incontinence and other voiding disorders. PATIENTS AND METHODS: The outcome measures from all patients in pivotal clinical trials who had undergone sacral nerve stimulation were analysed retrospectively. RESULTS: Neuromodulation was effective in several clinical studies; the response is durable and the benefit-risk profile good. CONCLUSION: Sacral nerve stimulation is becoming the standard of care for refractory overactive bladder and retention problems. The potential benefit of neuromodulation should be included in female urology and gynaecology training programmes.

Risk analysis: assessment, management and communication.

Import risk analysis is now a well-established discipline which aims to assist Veterinary Services to answer the following questions: 'What can go wrong?', 'How likely is it to go wrong?', 'What would be the consequences of it going wrong?' and 'What can be done to reduce either the likelihood or the consequences of it going wrong?'. Risk communication is that part of the overall process which, among other things, helps the decision-maker to determine whether a particular risk is acceptable or not. Good risk assessment and communication are dependent on clear formulation of the question to be answered. Scenario trees and influence diagrams are very useful tools in assessing and communicating risk. The authors outline the import risk analysis procedures adopted by the Veterinary Services of one Member Country of the OIE (World organisation for animal health).

Review on chronic pelvic pain from a urological point of view.

Chronic pelvic pain or interstitial cystitis (IC) is an enigmatic and frustrating condition to manage as physician and to cope with as patient. Patients report moderate to excruciating pain in the suprapubic and/or vaginal area, urgency and frequency (up to 50 micturitions per day), and disruption of their social life. Many patients are declared as drug addicted and neurotic. Social status and the number of sexual partners showed no correlation with incidence. Diagnosis of IC is made by exclusion. A number of pathophysiologic mechanisms have been proposed: changes in epithelial permeability, pelvic floor dysfunction, mastocytosis, activation of C-fibers, increase of nerve growth factors, and bradykinin. No single theory can explain IC.

Incontinence after radical prostatectomy: pathophysiology and management.

Despite improvements in surgical technique designed to preserve the functional integrity of the urethral sphincteric mechanism, incontinence after radical prostatectomy still occurs in many patients. Most patients have stress incontinence secondary to intrinsic sphincter deficiency, but many also have bladder dysfunction. The treatment of choice for post- prostatectomy stress incontinence is the artificial urinary sphincter. Other treatment options include collagen injection therapy and the male bulbourethral sling.

Interstitial cystitis: the painful bladder syndrome.

Interstitial cystitis (IC) is an enigmatic and frustrating condition to manage as a physician and to cope with as a patient. Many patients are declared as drug addicted and neurotic. Social status and number of sexual partners showed no correlation with incidence. Patients report moderate to excruciating pain in the suprapubic or vaginal area, urgency and frequency (up to 50 micturitions/d), and disruption of their social life. Diagnosis of IC is made by exclusion. Different pathophysiologic mechanisms have been proposed: changes in epithelial permeability, pelvic floor dysfunction, mastocytosis, activation of c-fibers, and increase of nerve growth factors and bradykinin. No single theory can explain IC.

Monitoring of renal function in patients with spinal cord injury.

OBJECTIVE: To assess the sensitivity of serum creatinine level in detecting clinically important and early deterioration of renal function in patients with spinal cord injury (SCI), and to evaluate the optimal method of determining creatinine clearance in these patients. PATIENTS AND METHODS: The serum creatinine level of 36 patients (25 paraplegics and 11 quadriplegics) was evaluated and compared with the corresponding measured creatinine clearance rate. Correlations were also assessed between the creatinine clearance measured by 24-h endogenous clearance, single-shot 99mTc-labelled diethylenetriamine pentaacetic acid (99mTc-DTPA) clearance technique, and the Cockcroft-Gault formula, to test their validity. RESULTS: Of the 36 patients 11 (31%) had a measured creatinine clearance of < 100 mL/min (mean 84.8) and a corresponding normal serum creatinine level. Creatinine clearance calculated by the Cockcroft-Gault formula did not correlate well with that measured by the 24-h endogenous clearance (r = 0.426) and 99mTc-DTPA clearance (r = 0. 366), overestimating creatinine clearance in all but three patients. The mean (SD) difference between the creatinine clearance measured by the 24-h and DTPA clearance technique was 17.7 (16.5)% and the correlation between these techniques was good (r = 0.71). CONCLUSION: Serum creatinine level is not sensitive in detecting early deterioration of renal function in patients with SCI. The Cockcroft-Gault formula generally significantly overestimates the true creatinine clearance and is not recommended. The 24-h endogenous creatinine clearance measured on appropriately collected urine samples is an acceptable accurate and practical method of determining glomerular filtration rate in patients with SCI.

Assessment of a new transurethral balloon dilation catheter in the treatment of urethral stricture disease.

OBJECTIVES: To assess a newly designed balloon dilation catheter for the treatment of urethral stricture disease. The dilating capability of the catheter, the tolerability and safety of the procedure, and its short-term efficacy were evaluated. METHODS: Fifty-one patients with urethral strictures underwent dilation with the UrethraMax or a coude tip balloon dilation catheter. Efficacy parameters included measurement of the American Urological Association symptom score and maximum urinary flow rate 3, 6, and 12 months after treatment. The adequacy of dilation and the degree of mucosal trauma and hematuria were assessed endoscopically, and patient pain was measured using a visual analog scale. RESULTS: Forty-three patients (84.3%) were successfully dilated, achieving a urethral caliber of 20F or greater. Dilation resulted in statistically significant improvements in both the mean American Urological Association symptom score and mean maximum urinary flow rate at 3 and 6 months. Mucosal trauma was mild in all but 4 cases, and no patient developed significant hematuria. The mean visual analog pain score was 3.9 (range 0.1 to 9.4). CONCLUSIONS: Balloon dilation is a safe, well-tolerated, office-based procedure that theoretically offers several advantages over sequential rigid dilation and internal urethrotomy. It is associated with minimal complications, and its short-term efficacy is acceptable. We regard this as the dilation procedure of choice and first-line therapy for most strictures.

A randomized double-blind study assessing 4 versus 8 mg. doxazosin for benign prostatic hyperplasia.

PURPOSE: We compare the efficacy of 4 versus 8 mg. doxazosin for benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 82 patients with benign prostatic hyperplasia successfully treated with 4 mg. doxazosin were randomized in a double-blind fashion to take 4 or 8 mg. Patients were evaluated with American Urological Association (AUA) symptom score, Boyarsky score, uroflowmetry and side effect profile before, and 1 and 3 months following randomization. RESULTS: Of the patients 42 and 40 were randomized to receive 4 and 8 mg. doxazosin, respectively. Both groups were similar with respect to patient age, baseline Boyarsky and AUA symptom scores, and baseline maximum urinary flow rate. At 3 months mean improvement from baseline plus or minus standard deviation in Boyarsky score was 0.6 +/- 6.5 and 4.9 +/- 6.6 in the 4 and 8 mg. groups (p <0.05), respectively, mean improvement in AUA symptom score was 1.6 +/- 5.3 and 5.3 +/- 8.0 (p <0.05), and mean maximum flow rate difference was -0.6 +/- 6.4 and +1.4 +/- 7.9 (p >0.05). Of the patients 7 and 8 in the 4 and 8 mg. groups dropped out of the study, and there were no statistical differences in side effects between dosages. CONCLUSIONS: A dose of 8 mg. doxazosin was more efficacious than 4 mg. and the side effects associated with both dosages appeared to be similar. The 8 mg. dose should be tried in patients who have not achieved an adequate therapeutic response to 4 mg. and are tolerating the medication. Consideration should be given to increasing the dosage to 8 mg. in patients who are clinically improved at lower dosages.

Eradication of Aujeszky's disease from New Zealand pig herds 1976-1997.

Aujeszky's disease was first diagnosed in the North Island of New Zealand in 1976. It has never been reported in the South Island. An industry-funded eradication programme was initiated in 1989 to eradicate the disease from the national pig herd. By using a combination of serological surveys, abattoir surveillance, test and slaughter, depopulation, vaccination and movement restrictions, Aujeszky's disease was eradicated by 1997.

A comparison of ambulatory and conventional urodynamic studies in men with borderline outlet obstruction.

OBJECTIVE: To compare detrusor function and outlet behaviour on ambulatory urodynamic monitoring (AUM) with conventional cystometrography in symptomatic men with borderline evidence of bladder outlet obstruction (BOO), as determined by conventional cystometrography, and to assess the usefulness of AUM in reclassifying this population of patients into obstructed and unobstructed groups. PATIENTS AND METHODS: Sixty-nine consecutive men (mean age 59.6 years) with lower urinary tract symptoms (mean International Prostate Symptom Score 19.1) and borderline BOO on a medium-fill conventional urodynamic study (CUS) were examined prospectively with AUM. Detrusor contractility, obstruction grade, maximal voiding detrusor pressure (pdet(max)), detrusor pressure at peak flow (pdet Qmax) and peak flow rate (Qmax) determined by both methods were compared. The incidence of detrusor instability (DI) detected by both modalities was also evaluated. RESULTS: There was considerable disagreement between the investigations during the voiding phase. Detrusor contractility was higher on AUM than on CUS (P= 0.003) and obstruction grade was significantly lower on AUM (P=0.018). There was no difference in pdet(max) nor pdet Qmax. The mean (95% confidence interval) Qmax was higher on AUM, at 12.9 (1.3) mL/s, than on CUS, at 8.9 (0.8) mL/s. On the Abrams-Griffiths nomogram the most significant changes were six men (10%) from equivocal to obstructed, seven (11%) from equivocal to unobstructed and two (3%) from obstructed to unobstructed on CUS and on AUM, respectively. Thus, in 24% of patients there was a potentially clinically significant change resulting from the information generated by AUM. DI was identified on CUS in 26 (41%) men and on AUM in 25 (40%); 35 men (56%) had evidence of DI on either AUM or CUS. CONCLUSION: The significant disagreement between the findings on CUS and AUM suggests that the conditions under which pressure-flow investigations are carried out significantly affect findings in borderline cases. The reclassification of patients by AUM into obstructed and unobstructed groups occurs in 24% and may be clinically relevant. AUM appears to be complementary to CUS in the assessment of men who are borderline for obstruction on conventional testing, but the clinical implications of this have yet to be determined.

An assessment of the comprehension of the American Urological Association Symptom Index.

PURPOSE: We determine the reading grade level of the American Urological Association (AUA) symptom index, and assessed patient ability to read and understand the index using a standardized reading and IQ test. MATERIALS AND METHODS: The reading grade level required to read and understand the AUA symptom index was determined using the Spache and Dale-Chall readability formulas. A total of 202 men a mean of 66.1 years old completed the AUA symptom index, Wonderlic personnel test and scholastic level examination, and revised Ohio literacy test. Patients were instructed to report any difficulty in reading or understanding the AUA symptom score. RESULTS: According to the Spache and Dale-Chall readability formulas, the AUA symptom index requires a grade 6 reading level. Of the 202 patients 30 (14.9%) did not complete the symptom index due to an inability to read it (28, 13.9%) and poor comprehension (2, 1%). Tested mean IQ and reading grade level was 91.7 and 11, respectively. CONCLUSIONS: A grade 6 reading level is required to read and understand the AUA symptom index. A significant percentage of patients cannot read the index and require assistance from others for its completion. This assistance may introduce significant interviewer bias, potentially altering study outcome.