Does choice of anesthesia during stage 1 sacral neuromodulation testing influence outcomes?

INTRODUCTION: Staged sacral neuromodulation (SNM) testing has been shown to have a high rate of progression to permanent implantation for the management of voiding dysfunction. Stage 1 lead placement (SNM-I) can be performed under monitored anesthesia care (MAC) or general anesthesia (GA). MAC allows for interpretation of sensory and motor responses to optimize lead placement while GA only permits for motor assessment. However, patient discomfort and movement can make lead placement challenging during MAC. Herein we evaluate whether the anesthesia type impacts the progression rate to permanent implantation (SNM-II). MATERIALS AND METHODS: A retrospective chart review was performed for patients who underwent SNM-I in the operating room for wet overactive bladder between 2005 and 2023. Patients were divided into two groups based on the type of anesthesia used, MAC or GA. Clinical variables and progression to SNM-II were compared between cohorts. Progression to SNM-II was based on ≥50% symptomatic improvement during a 1-2 week trial period following SNM-I. RESULTS: Of 121 patients included in the study, 95 (79%) underwent MAC and 26 (21%) GA for SNM-I. No difference in the progression rate to SNM-II was noted between groups (MAC, 68/95 patients, 72%; GA, 19/26, 73%; p = 0.39). We also found no difference when comparing the GA group to the 26 most recent MAC patients (MAC, 20/26 patients, 77%; GA, 19/26, 73%; p = 0.48). CONCLUSION: Types of anesthesia for SNM-I did not affect rate of progression to SNM-II. The result lends support to the reliance on motor responses alone for lead placement during SNM-I.

Is a 50% improvement threshold adequate to justify progression from sacral neuromodulation testing to implant?

PURPOSE: A ≥50% subjective improvement in urinary symptoms during sacral neuromodulation testing (SNM-I) is currently used as the indication for progression to second-stage implantation (SNM-II). While most patients will have successful SNM-I and proceed to SNM-II, deterioration in efficacy over time has been reported. It remains unclear if the durability of efficacy is related to the initial symptom reduction. We sought to determine if the degree of improvement after SNM-I is sufficient to predict long-term success. METHODS: The records of all patients who underwent sacral neuromodulation (SNM) for overactive bladder were reviewed. Subjects were divided into those who reported 50%-75% improvement (Group 1) and more than 75% improvement (Group 2) after SNM-I. Differences in clinical variables and long-term device efficacy were compared between groups. RESULTS: Of 213 patients who underwent SNM-I, 137 underwent permanent device implantation. A total of 76 (55%) and 61 (45%) patients reported 50%-75% (Group 1) and more than 75% (Group 2) symptomatic improvement, respectively. With a mean follow-up of 46 months, 44% of Group 1 patients and 68% of Group 2 patients still had a functioning device providing the symptomatic benefit (p = 0.007). Univariate analyses identified the presence of stress urinary incontinence at baseline and having a more than 75% improvement after SNM-I as predictors of long-term functional success. CONCLUSIONS: Compared to patients reporting 50%-75% symptomatic reduction after SNM-I, individuals with a more than 75% improvement during SNM-I were more likely to maintain device efficacy over time. Additional study is warranted to determine if the improvement threshold for progression to SNM-II should be increased.

Factors associated with recurrent urinary tract infections in spinal cord injured patients who use intermittent catheterization.

INTRODUCTION: Urinary Tract Infection (UTI) has been cited as the primary cause of morbidity in patients with history of spinal cord injury (SCI). Despite the significance of recurrent UTI (rUTI) in this population, the causative physiologic and patient characteristics are not well described. We sought to assess associations between demographic, clinical and urodynamic variables and rUTI. MATERIALS AND METHODS: The records of 136 individuals with SCI who perform clean intermittent catheterization (CIC) were retrospectively reviewed. All had a video urodynamics study (VUDS) available for analysis. Individuals were divided into non-recurrent (< 3/year) or rUTI (≥ 3/year) groups. Differences between the cohorts were analyzed. Multivariable logistic regression was performed to determine associations between various demographic, clinical, and VUDS variables and rUTI. RESULTS: Self-reported rUTI were noted in 58 of 136 individuals. Of 124 individuals with urinary culture results, African American race (43.3% vs. 22.3%) and 'Other' race (13.3% vs. 8.5%) made up larger proportions in the rUTI group. Female gender (OR 4.96, 95% CI [1.44-17.13]) and African American race (OR 5.16, 95% CI [1.80-14.79]) were increasingly associated with rUTI on multivariable logistic regression. Shorter interval since injury was also significantly associated with recurrent infections with each year since injury indicating diminished likelihood (OR 0.91, 95% CI [0.82-0.99]). There were no significant differences in VUDS variables between groups and none were significant on regression as potential determinants of rUTI. CONCLUSIONS: Patient race, gender, and time since SCI appear to have significant associations with rUTI in individuals with SCI using CIC. However, VUDS variables were not found to be significantly associated with rUTI.

Designing a survey to monitor multi-scale impacts of agri-environment schemes on mobile taxa.

Agri-environment schemes (AES) are key mechanisms to deliver conservation policy, and include management to provide resources for target taxa. Mobile species may move to areas where resources are increased, without this necessarily having an effect across the wider countryside or on populations over time. Most assessments of AES efficacy have been at small spatial scales, over short timescales, and shown varying results. We developed a survey design based on orthogonal gradients of AES management at local and landscape scales, which will enable the response of several taxa to be monitored. An evidence review of management effects on butterflies, birds and pollinating insects provided data to score AES options. Predicted gradients were calculated using AES uptake, weighted by the evidence scores. Predicted AES gradients for each taxon correlated strongly, and with the average gradient across taxa, supporting the co-location of surveys across different taxa. Nine 1 × 1 km survey squares were selected in each of four regional blocks with broadly homogenous background habitat characteristics. Squares in each block covered orthogonal contrasts across the range of AES gradients at local and landscape scales. This allows the effects of AES on species at each scale, and the interaction between scales, to be tested. AES options and broad habitats were mapped in field surveys, to verify predicted gradients which were based on AES option uptake data. The verified AES gradient had a strong positive relationship with the predicted gradient. AES gradients were broadly independent of background habitat within each block, likely allowing AES effects to be distinguished from potential effects of other habitat variables. Surveys of several mobile taxa are ongoing. This design will allow mobile taxa responses to AES to be tested in the surrounding countryside, as well as on land under AES management, and potentially in terms of population change over time. The design developed here provides a novel, pseudo-experimental approach for assessing the response of mobile species to gradients of management at two spatial scales. A similar design process could be applied in other regions that require a standardized approach to monitoring the impacts of management interventions on target taxa at landscape scales, if equivalent spatial data are available.

Intradetrusor botulinum toxin injections (300 units) for the treatment of poorly compliant bladders in patients with adult neurogenic lower urinary tract dysfunction.

AIMS: To evaluate the therapeutic effects of intradetrusor onabotulinum toxin A (BTX) injections in patients with adult neurogenic lower urinary tract dysfunction (ANLUTD) and medically refractory poorly compliant bladders. METHODS: We retrospectively evaluated patients with urodynamic studies (UDS)-proven, medically refractory impaired bladder compliance (≤20 mL/cm H2 O) secondary to spinal myelopathy treated with 300 units of BTX cystoscopically injected into the detrusor muscle. Objective improvement in compliance was defined as an increase ≥5 mL/cm H2 O on repeat urodynamics. Characteristics were compared between patients who demonstrated symptomatic and objective improvement following treatment versus those without. RESULTS: Seventy-one individuals were included in the final analysis. Mean patient age was 37.2 years (range: 18-78) and ANLUTD duration was 14.5 years (range: 1-34). Average pre-injection bladder compliance was 9.2 mL/cm H2 O (range: 3.0-16.7). After treatment with BTX, 37 of 71 (52%) patients reported subjective reductions in lower urinary tract symptoms. Repeat UDS demonstrated objective bladder compliance improvements in 22 of 71 (31%). Individuals with shorter time intervals since neurologic injury responded better to BTX than those with longer durations (P = .032). CONCLUSION: BTX injections significantly improved symptoms and bladder compliance in 31% of ANLUTD patients with medical refractory poorly compliant bladders.

A re-evaluation of teenage sunbed use following the introduction of banning legislation for under 18-year-olds.

BACKGROUND: There is little information on the effectiveness of introducing age restriction legislation alone to reduce the rate of sunbed usage by teenagers. Prior to the Public Health (Sunbed) Act of 2014 prohibiting the use of sunbeds in under 18-year-olds in Ireland we reported the rate of sunbed use at 7.5%. OBJECTIVES: The aim of the study was to compare the rate of sunbed usage among Irish teenagers before and after the introduction of banning legislation to determine if it had the desired effect of reducing its rate of use. METHODS: In a cross-sectional survey, students from the same schools as in our previous study completed an anonymous, written questionnaire pertaining to sunbed usage. RESULTS: In total, 783 questionnaires, from 13 schools across Ireland, were completed. The rate of sunbed use in the current study was 7.2%, compared to 7.5% in the pre-ban study, (P = 0.76). A higher rate of sunbed use was observed in Dublin schools and female public students. CONCLUSION: Our study suggests that legislation alone is ineffective at reducing sunbed usage in a teenage population. A multifaceted approach is required that includes enforcement of the legislation together with targeted public education and awareness campaigns using all aspects of the media.

The tension between efficiency and effectiveness: a study of dietetic practice in primary care.

BACKGROUND: Primary healthcare dietitians have a vital role to play in the prevention and management of chronic disease. Working in primary care requires efficient and effective management of practice to ensure client and practitioner needs are met. The present study aimed to explore the way in which primary care dietitians in Australia view the constructs of efficiency and effectiveness within the context of their practice. METHODS: The study used an exploratory qualitative design within a pragmatist framework. Individual semi-structured telephone interviews were conducted with Australian primary care dietitians. All interviews were audio-recorded, transcribed verbatim and analysed using an inductive thematic approach. RESULTS: Twenty dietitians (17 females) working as private practitioners in primary care from three Australian states participated in the present study. Three themes emerged from the data. The first theme revealed that seeking efficiency and especially effectiveness were important to primary care dietitians and that there was a tension between the two. The second theme identified that efficiency and effectiveness are influenced by personal and structural factors. The final theme explored how dietitians are actively seeking ways to be more efficient and effective, including supportive networks, as well as the utilisation of technology. CONCLUSIONS: Achieving a balance between efficiency and effectiveness in primary care dietetics is challenging to practitioners, who may require further training and support to enhance productivity, time management and resource utilisation. Structured issues exist for the workface. Further studies are required to quantify these findings and to explore whether it is possible to optimise efficiency and effectiveness and achieve sustainability of the dietetic workforce in primary care.

Is mesenteric defect closure needed in urologic surgery using ileum?

INTRODUCTION: Classic surgical teaching advocates for closure of the mesenteric defect (MD) after bowel anastomosis but the necessity is controversial. We sought to evaluate the necessity of MD closure at the time of harvest of ileum for genitourinary reconstructive surgery (GURS) by analyzing the incidence of early and late gastrointestinal adverse events (GIAE) in patients with and without MD closure. MATERIALS AND METHODS: A retrospective review was conducted on patients undergoing urologic reconstruction with ileum to identify incidence of ileus, small bowel obstruction (SBO), gastrointestinal (GI) fistula and stoma complications. Patient and procedure variables were analyzed to identify risk factors for GIAE. RESULTS: A total of 288 patients met inclusion criteria and 93% of GURS was for urinary diversion following cystectomy. MD was closed in 194 cases (67%). Median follow up was 19 months. Early (< 30 day) GIAE rates were 16.5% (n = 32) and 21.3% (n = 20) in the closure and non-closure groups, respectively (p = 0.22). The rate of early ileus/SBO requiring nasogastric tube decompression or laparotomy were similar after closure (15.0%) and non-closure (21.3%) (p = .18). The late GIAE rates were 5.7% (n = 11) and 6.4% (n = 6) in the closure and non-closure cohorts, respectively (p = 0.56). The rate of late SBO were similar and no cases of early or late SBO in either cohort were due to internal herniation. On multivariate analysis, increasing BMI was associated with both early and late GIAE. CONCLUSIONS: After harvesting ileum for urologic reconstruction, the MD can safely be left open as we found no association between non-closure and early or late GIAE..

The Impact of Age and Deprivation on NHS Payment Claims for Domiciliary Dental Care in England.

Domiciliary dental care provides care to patients who are unable to attend dental clinics for a variety of reasons. OBJECTIVE: This research analyses NHS payment claim data for domiciliary dental care in England to identify any variations by area and determine whether age or deprivation are associated with levels of domiciliary care provided. METHODS: Publicly available data from the NHS Business Services Authority and demographic data from additional public datasets were linked to assess the variation in claims made for NHS domiciliary activity across England. Associations with factors such as the proportion of older people and deprivation were investigated using correlation, univariable and multivariable regression models. RESULTS: There was substantial variation by area in the number of NHS payment claims made for domiciliary activity and a statistically significant but very weak positive correlation between the population of each area and the number of domiciliary payment claims made. Correlation, univariable and multivariable analyses demonstrated positive but weak associations between area deprivation measures and the number of claims per population. There was little evidence of an association between proportions of older adults and numbers of domiciliary claims per population. CONCLUSION: As older and more deprived populations are those most likely to require domiciliary dental care, these results suggest that access to services is variable and not always based upon need. This highlights a potential need to reconsider the criteria upon which this type of dental care is offered and the commissioning of these services in different localities.

Management of Bone Fragility in Primary Care in Ireland.

This study evaluated the prevention of bone fragility fractures in a representative sample of four Irish general practices. The clinical records of 243 patients potentially at risk of bone fragility were studied. One hundred and fourteen (47%) had a dual energy x-ray absorptiometry (DEXA) scan. Osteoporosis was established in 42 (17%) and osteopaenia in 28 (11%). One hundred and fifty-two (63%) were currently being prescribed bisphosphonates. Thirty-four (22%) of those on bisphosphonates did not have a baseline DEXA scan performed prior to commencing treatment and further analysis did not show a clear rationale for initiation of the treatment in this group of patients. Forty-six (30%) patients on bisphosphonates had been prescribed them for over 5 years without any apparent review to see if they were still indicated. There was no record of any of the practices having carried out a fracture risk score assessment prior to commencing bone fragility treatment. The implications are that bone fragility management warrants urgent review.

In Vitro Induction of Human Regulatory T Cells Using Conditions of Low Tryptophan Plus Kynurenines.

Thymic regulatory T cells (tTregs) and induced regulatory T cells (iTregs) suppress murine acute graft-versus-host disease (GVHD). Previously, we demonstrated that the plasmacytoid dendritic cell indoleamine 2,3-dioxygenase (IDO) fosters the in vitro development of human iTregs via tryptophan depletion and kynurenine (Kyn) metabolites. We now show that stimulation of naïve CD4+ T cells in low tryptophan (low Trp) plus Kyn supports human iTreg generation. In vitro, low Trp + Kyn iTregs and tTregs potently suppress T effector cell proliferation equivalently but are phenotypically distinct. Compared with tTregs or T effector cells, bioenergetics profiling reveals that low Trp + Kyn iTregs have increased basal glycolysis and oxidative phosphorylation and use glutaminolysis as an energy source. Low Trp + Kyn iTreg viability was reliant on interleukin (IL)-2 in vitro. Although in vivo IL-2 administration increased low Trp + Kyn iTreg persistence on adoptive transfer into immunodeficient mice given peripheral blood mononuclear cells to induce GVHD, IL-2-supported iTregs did not improve recipient survival. We conclude that low Trp + Kyn create suppressive iTregs that have high metabolic needs that will need to be addressed before clinical translation.

Less is more-A pilot study evaluating one to three intradetrusor sites for injection of OnabotulinumtoxinA for neurogenic and idiopathic detrusor overactivity.

AIMS: To determine if minimizing the number of onabotulinumtoxinA (BTX) injection sites to one to three locations provides similar clinical efficacy and duration of effect compared to the established technique in treating patients with neurogenic (NDO) or idiopathic detrusor overactivity (IDO). METHODS: Prospective data were collected on BTX naïve patients with NDO or IDO who were intolerant or refractory to oral medications. Patients were treated with 100-300 U of BTX via one to three injection sites. Patients completed the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) prior to and after treatment. The primary endpoint was defined as ICIQ-SF score improvement of >5 points. Secondary endpoints included subjective success, complete continence, quality of life score, post void residual (PVR), duration of effect and adverse events. RESULTS: Fourty-five patients (22 IDO, 23 NDO) were included. ICIQ-SF score improvement of >5 points was achieved in 73% (IDO 55%, NDO 91%) and the subjective success rate was 69% (50% IDO, 87% NDO). 52% of NDO patients attained complete continence. PVR increased by a mean of 32 and 156 ml in the IDO and NDO groups. Hematuria occurred in 6.7% and symptomatic urinary tract infection occurred in 11.1%. No systemic BTX adverse events occurred. Mean duration of effect was 31 weeks. CONCLUSIONS: Our technique for administering BTX via one to three intradetrusor injection sites has similar clinical efficacy and rates of adverse events compared to the established technique for treating patients with IDO and NDO. Neurourol. Urodynam. 36:1104-1107, 2017. © 2016 Wiley Periodicals, Inc.

Seeking help in times of economic hardship: access, experiences of services and unmet need.

BACKGROUND: Economic recessions are often accompanied by increased levels of psychological distress and suicidal behaviour in affected populations. Little is known about the experiences of people seeking help for employment, financial and benefit-related difficulties during recessions. We investigated the experiences of people struggling financially in the aftermath of the Great Recession (2008-9) - including some who had self-harmed - and of the frontline support staff providing assistance. METHODS: Interviews were conducted with three groups of people in two cities: i) people who had self-harmed due to employment, financial or benefit concerns (n = 19) ('self-harm'); ii) people who were struggling financially drawn from the community (n = 22), including one focus group) ('community'); iii) and frontline staff from voluntary and statutory sector organisations (e.g., Job Centres, Debt Advice and counselling agencies) providing support services to the groups (n = 25, including 2 focus groups) ('service providers'). Data were analysed using the constant comparison method. RESULTS: Service provision was described by people as confusing and difficult to access. The community sample reported considerably more knowledge and access to debt advice than the participants who had self-harmed - although both groups sought similar types of help. The self-harm group exhibited greater expectation that they should be self-reliant and also reported lower levels of informal networks and support from friends and relatives. They had also experienced more difficult circumstances such as benefit sanctions, and most had pre-existing mental health problems. Both self-harm and community groups indicated that practical help for debt and benefit issues would be the most useful - a view supported by service providers - and would have particularly helped those who self-harmed. CONCLUSION: Interventions to identify those in need and aid them to access practical, reliable and free advice from support agencies could help mitigate the impact on mental health of benefit, debt and employment difficulties for vulnerable sections of society.

Isolation of subtelomeric sequences of porcine chromosomes for translocation screening reveals errors in the pig genome assembly.

Balanced chromosomal aberrations have been shown to affect fertility in most species studied, often leading to hypoprolificacy (reduced litter size) in domestic animals such as pigs. With an increasing emphasis in modern food production on the use of a small population of high quality males for artificial insemination, the potential economic and environmental costs of hypoprolific boars, bulls, rams etc. are considerable. There is therefore a need for novel tools to facilitate rapid, cost-effective chromosome translocation screening. This has previously been achieved by standard karyotype analysis; however, this approach relies on a significant level of expertise and is limited in its ability to identify subtle, cryptic translocations. To address this problem, we developed a novel device and protocol for translocation screening using subtelomeric probes and fluorescence in situ hybridisation. Probes were designed using BACs (bacterial artificial chromosomes) from the subtelomeric region of the short (p-arm) and long (q-arm) of each porcine chromosome. They were directly labelled with FITC or Texas Red (p-arm and q-arm respectively) prior to application of a 'Multiprobe' device, thereby enabling simultaneous detection of each individual porcine chromosome on a single slide. Initial experiments designed to isolate BACs in subtelomeric regions led to the discovery of a series of incorrectly mapped regions in the porcine genome assembly (from a total of 82 BACs, only 45 BACs mapped correctly). Our work therefore highlights the importance of accurate physical mapping of newly sequenced genomes. The system herein described allows for robust and comprehensive analysis of the porcine karyotype, an adjunct to classical cytogenetics that provides a valuable tool to expedite efficient, cost effective food production.

Hidradenitis Suppurativa and Crohn's Disease: A Case Series.

Hidradenitis Suppurativa (HS) is characterized by chronic recurrent abscesses, nodules and draining sinus tracts with scar formation. Cutaneous Crohn's Disease (CD) may also present similarly. We wished to identify and describe an Irish cohort with combined HS and CD, with a view to a better recognition of clinical manifestations and understanding of the pathophysiology underlying these two overlapping conditions. Cases were identified using the HIPE Code at Tallaght Hospital from 1990-2014 and retrospective review was performed. Seven patients with both HS and CD were identified, 5(71%) female. The median age of diagnosis with both conditions was 37 years. In all cases, CD had preceded the diagnosis of HS. All patients smoked. Six had an increased BMI and 43% had additional autoimmune conditions. All patients required treatment with a TNF-alpha inhibitor for HS with 5 of 6 subjects having reduced frequency of flare ups and clinically less active HS on follow up.

Interventions to Improve the Treatment of Malaria in an Acute Teaching Hospital in Ireland.

Malaria is the most serious parasitic infection. At our institution over a two year period there were treatment errors in 18% (n=3) of cases. The aim of this multidisciplinary study was to ensure appropriate and timely treatment of malaria by implementation of a cluster of interventions: reconfiguration of existing guidelines, provision of prescribing information; delivery of education sessions to front-line staff and enabling rapid access to medication. Staff feedback was assessed through a questionnaire. Perceived benefits gained included awareness of guidelines (91%, n= 39), how to diagnose (81%, n =35), how to treat (86%, n=37), that treatment must be prompt (77%, n=33) and where to find treatment out of hours (84%, n=36). 'Others' perceived benefits (5% n= 2) noted referred to treatment in pregnancy. Going forward, a programme of on-going staff education, repeated audits of guideline compliance and promotion of reporting of medication errors should help ensure that these benefits are sustained.

Bile acids destabilise HIF-1α and promote anti-tumour phenotypes in cancer cell models.

BACKGROUND: The role of the microbiome has become synonymous with human health and disease. Bile acids, as essential components of the microbiome, have gained sustained credibility as potential modulators of cancer progression in several disease models. At physiological concentrations, bile acids appear to influence cancer phenotypes, although conflicting data surrounds their precise physiological mechanism of action. Previously, we demonstrated bile acids destabilised the HIF-1α subunit of the Hypoxic-Inducible Factor-1 (HIF-1) transcription factor. HIF-1 overexpression is an early biomarker of tumour metastasis and is associated with tumour resistance to conventional therapies, and poor prognosis in a range of different cancers. METHODS: Here we investigated the effects of bile acids on the cancer growth and migratory potential of cell lines where HIF-1α is known to be active under hypoxic conditions. HIF-1α status was investigated in A-549 lung, DU-145 prostate and MCF-7 breast cancer cell lines exposed to bile acids (CDCA and DCA). Cell adhesion, invasion, migration was assessed in DU-145 cells while clonogenic growth was assessed in all cell lines. RESULTS: Intracellular HIF-1α was destabilised in the presence of bile acids in all cell lines tested. Bile acids were not cytotoxic but exhibited greatly reduced clonogenic potential in two out of three cell lines. In the migratory prostate cancer cell line DU-145, bile acids impaired cell adhesion, migration and invasion. CDCA and DCA destabilised HIF-1α in all cells and significantly suppressed key cancer progression associated phenotypes; clonogenic growth, invasion and migration in DU-145 cells. CONCLUSIONS: These findings suggest previously unobserved roles for bile acids as physiologically relevant molecules targeting hypoxic tumour progression.

Cystectomy and Urinary Diversion for the Management of a Devastated Lower Urinary Tract Following Prostatic Cryotherapy and/or Radiotherapy.

INTRODUCTION: We investigated the outcomes and quality of life measures in men who underwent cystectomy and urinary diversion for devastating lower urinary tract toxicity after prostatic radiotherapy and/or cryotherapy for the treatment of prostate cancer. METHODS: Records of patients who underwent cystectomy and urinary diversion for the management of a devastated lower urinary tract following prostatic radiotherapy or cryotherapy were reviewed retrospectively. A postoperative, retrospective quality of life (QOL) survey was designed specific to this patient subset and obtained by telephone interview. RESULTS: Extirpative surgery with urinary diversion for management of a devastated lower urinary tract was performed on 15 patients with a mean age of 72 years (range 63-82). Toxicities leading to bladder removal included bladder neck contractures, prostatic necrosis, incontinence, osteomyelitis, bladder calculi, fistulae, urethral strictures, abscesses, necrotizing fasciitis, and radiation/hemorrhagic cystitis. The mean number of failed conservative, minimally invasive interventions per patients prior to cystectomy was 3.7 (range 1-12). The average time period from major complication following radiotherapy/cryotherapy to cystectomy was 29.1 months (range 5-65). The QOL survey showed all of the patients who completed the survey (n = 13) would undergo the procedure again and 11 (85%) would have undergone the procedure an average of 13.2 months sooner (range 5-36). CONCLUSION: Toxicities secondary to prostatic radiotherapy or cryotherapy may be debilitating. Our results demonstrate that cystectomy with urinary diversion can improve QOL in patients with a devastated lower urinary tract.

Peripheral chemoreceptors tune inspiratory drive via tonic expiratory neuron hubs in the medullary ventral respiratory column network.

Models of brain stem ventral respiratory column (VRC) circuits typically emphasize populations of neurons, each active during a particular phase of the respiratory cycle. We have proposed that "tonic" pericolumnar expiratory (t-E) neurons tune breathing during baroreceptor-evoked reductions and central chemoreceptor-evoked enhancements of inspiratory (I) drive. The aims of this study were to further characterize the coordinated activity of t-E neurons and test the hypothesis that peripheral chemoreceptors also modulate drive via inhibition of t-E neurons and disinhibition of their inspiratory neuron targets. Spike trains of 828 VRC neurons were acquired by multielectrode arrays along with phrenic nerve signals from 22 decerebrate, vagotomized, neuromuscularly blocked, artificially ventilated adult cats. Forty-eight of 191 t-E neurons fired synchronously with another t-E neuron as indicated by cross-correlogram central peaks; 32 of the 39 synchronous pairs were elements of groups with mutual pairwise correlations. Gravitational clustering identified fluctuations in t-E neuron synchrony. A network model supported the prediction that inhibitory populations with spike synchrony reduce target neuron firing probabilities, resulting in offset or central correlogram troughs. In five animals, stimulation of carotid chemoreceptors evoked changes in the firing rates of 179 of 240 neurons. Thirty-two neuron pairs had correlogram troughs consistent with convergent and divergent t-E inhibition of I cells and disinhibitory enhancement of drive. Four of 10 t-E neurons that responded to sequential stimulation of peripheral and central chemoreceptors triggered 25 cross-correlograms with offset features. The results support the hypothesis that multiple afferent systems dynamically tune inspiratory drive in part via coordinated t-E neurons.