Does industry-sponsored education foster overdiagnosis and overtreatment of depression, osteoporosis and over-active bladder syndrome? An Australian cohort study

ObjectivesTo investigate patterns of industry-sponsored educational events that focus on specific health conditions for which there are concerns about overdiagnosis and overtreatment.Design and settingThis retrospective cohort study examines publicly reported industry-sponsored events in Australia from October 2011 to September 2015 for three conditions potentially subject to overdiagnosis and overtreatment: depression, osteoporosis and overactive bladder. We used a database of transparency reports to identify events with a focus on depression, osteoporosis and overactive bladder and compared these with other sponsored events. We hypothesised that companies marketing treatments for each condition would sponsor related events and that target audiences would mainly work in primary care, reflecting a broad patient population.Main outcome measuresEvent and attendee characteristics, sponsoring companies, related marketed treatments, cost-effectiveness ratings and dispensing rates.ResultsOver the study period, we identified 1567 events focusing on depression, 1375 on osteoporosis and 190 on overactive bladder (total n=3132, with 96 660 attendees). These events were attended by primary care doctors more often than sponsored events without a focus on these three conditions: relative risk (RR)=3.06 (95% CI 2.81 to 3.32) for depression, RR=1.48 (95% CI 1.41 to 1.55) for osteoporosis and RR=2.59 (95% CI 2.09 to 3.21) for overactive bladder. Servier, which markets agomelatine and AstraZeneca (quetiapine) sponsored 51.2% and 23.0% of depression events, respectively. Amgen and GlaxoSmithKline, which co-market denosumab, sponsored 49.5% of osteoporosis events and Astellas and Commonwealth Serum Laboratories (CSL) (mirabegron and solifenacin) sponsored 80.5% of overactive bladder events.ConclusionsThis 4-year overview of industry-sponsored events on three overdiagnosed and overtreated conditions found that primary care clinicians were often targeted, dinner was often provided and that a few companies sponsored most events. In most cases, sponsors’ products are not cost-effective choices for the specified condition. This pattern highlights the need for professional education to be free of commercial sponsorship.</jats:sec

Neuromodulation in neurogenic bladder.

While neuromodulation is a well-established treatment option for patients with non-neurogenic overactive bladder and urinary retention, its applicability to the neurogenic bladder population has only recently been examined more in depth. In this article we will discuss the outcomes, contraindications, and special considerations of sacral and percutaneous tibial nerve stimulation (PTNS) in patients with neurogenic lower urinary tract dysfunction

Impact of onabotulinumtoxinA on quality of life and practical aspects of daily living : a pooled analysis of two randomized controlled trials

Objective: To evaluate the impact of onabotulinumtoxinA on individual domains of the quality of life questionnaires in a pooled analysis of two phase 3 trials in overactive bladder patients with urinary incontinence who were inadequately managed by >= 1 anticholinergic. Methods: Patients received intradetrusor injections of onabotulinumtoxinA 100U (n = 557) or placebo (n = 548). The proportions of patients with a positive response (condition "greatly improved" or "improved") on the Treatment Benefit Scale, and changes in Incontinence Quality of Life scores and King's Health Questionnaire domain scores were analyzed in the overall population and subgroups with clean intermittent catheterization use and urinary tract infection status during the first 12 weeks of treatment. Responses to individual King's Health Questionnaire items were also assessed. Results: Significantly greater proportions of onabotulinumtoxinA-treated patients achieved positive Treatment Benefit Scale response versus placebo (61.8% vs 28.0%; P < 0.001). OnabotulinumtoxinA showed significantly greater improvements versus placebo in Incontinence Quality of Life total (22.5 vs 6.6), Incontinence Quality of Life subscale scores and all domains of the King's Health Questionnaire. Notably, a similar trend was observed regardless of clean intermittent catheterization/urinary tract infection status. Additionally, onabotulinumtoxinA resulted in significantly greater improvements than the placebo in practical aspects of patients daily lives, including pad use, need to change undergarments, sleep, relationship with partner and work life/daily activities. Conclusion: In overactive bladder patients with urinary incontinence, onabotulinumtoxinA 100U demonstrated significant improvements across the individual domains of the quality of life questionnaires, regardless of clean intermittent catheterization or urinary tract infection status, and provided a positive impact on practical aspects of patients' daily lives

Patient-Reported Side Effects of Intradetrusor Botulinum Toxin Type A for Idiopathic Overactive Bladder Syndrome

Objective: The aim of the study was a prospective assessment of patient-reported side effects in an open-label study after intradetrusor botulinum toxin injections for idiopathic overactive bladder (OAB). Patients and Methods: Botulinum toxin A injection was performed in 56 patients with idiopathic OAB. Patients were followed up for 6 months concerning side effects and patients' satisfaction. Results: Different types of side effects were assessed such as dry mouth (19.6%), arm weakness (8.9%), eyelid weakness (8.9%), leg weakness (7.1%), torso weakness (5.4%), impaired vision (5.4%) and dysphagia (5.4%). In all cases, symptoms were mild and transient. Urological complications such as gross hematuria (17.9%), acute urinary retention (8.9%) and acute urinary tract infection (7.1%) were noticed. In all cases, acute urinary retention was transient and treated with temporary intermittent self-catheterization. There was no statistically significant correlation between dosage and observed side effects. Patients' satisfaction rate was high (71.4%). Conclusion: Intradetrusor injection of botulinum toxin was associated with a high rate of neurourological side effects. In general, side effects were transient, mild and did not require special treatment. Copyright (C) 2010 S. Karger AG, Base

A Randomized Controlled Trial of Device Guided, Slow-Paced Respiration in Women with Overactive Bladder Syndrome.

PurposeWe evaluated the effects of device guided, slow-paced respiration on urgency associated urinary symptoms, perceived stress and anxiety, and autonomic function in women with overactive bladder syndrome.Materials and methodsWe performed a randomized, parallel group trial of slow-paced respiration to improve perceived stress and autonomic dysfunction as potential contributors to overactive bladder. Ambulatory women who reported at least 3 voiding or incontinence episodes per day associated with moderate to severe urgency were randomized to use a portable biofeedback device to practice daily, slow, guided breathing exercises or a control device which appeared identical and was reprogrammed to play music without guiding breathing. During 12 weeks we evaluated changes in urinary symptoms by voiding diaries, perceived stress and anxiety by validated questionnaires, and autonomic function by heart rate variability and impedance cardiography.ResultsIn the 161 randomized participants, including 79 randomized to paced respiration and 82 randomized to the control group, the average ± SD baseline frequency of voiding or incontinence associated with moderate to severe urgency was 6.9 ± 3.4 episodes per day. Compared to controls the participants randomized to paced respiration demonstrated greater improvement in perceived stress (average Perceived Stress Scale score decrease 2.8 vs 1.1, p=0.03) but not in autonomic function markers. During 12 weeks the average frequency of voiding or incontinence associated with moderate to severe urgency, which was the study primary outcome, decreased by a mean of 0.9 ± 3.2 episodes per day but no significant between group difference was detected.ConclusionsAmong women with overactive bladder slow-paced respiration was associated with a modest improvement in perceived stress during 12 weeks. However, it was not superior to a music listening control for reducing urinary symptoms or changing autonomic function

Stimulation of the tibial nerve: a protocol for a multicentred randomised controlled trial for urinary problems associated with Parkinson’s disease—STARTUP

Introduction Parkinson’s disease is the second most common chronic neurodegenerative condition with bladder dysfunction affecting up to 71%. Symptoms affect quality of life and include urgency, frequency, hesitancy, nocturia and incontinence. Addressing urinary dysfunction is one of the top 10 priority research areas identified by the James Lind Alliance and Parkinson’s UK. Objectives Conduct a randomised controlled trial (RCT) targeting people with Parkinson’s disease (PwP) who have self-reported problematic lower urinary tract symptoms, investigating the effectiveness of transcutaneous tibial nerve stimulation (TTNS) compared with sham TTNS. Implement a standardised training approach and package for the correct application of TTNS. Conduct a cost-effectiveness analysis of TTNS compared with sham TTNS. Methods and analysis An RCT of 6 weeks with twice weekly TTNS or sham TTNS. Participants will be recruited in 12 National Health Service neurology/movement disorder services, using a web-based randomisation system, and will be shown how to apply TTNS or sham TTNS. Participants will receive a weekly telephone call from the researchers during the intervention period. The trial has two coprimary outcome measures: International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form and the International Prostate Symptom Score. Secondary outcomes include a 3-day bladder diary, quality of life, acceptability and fidelity and health economic evaluation. Outcomes will be measured at 0, 6 and 12 weeks. A sample size of 208 randomised in equal numbers to the two arms will provide 90% power to detect a clinically important difference of 2.52 points on the Internatioanl Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF) and of 3 points in the International Prostate Symptom Score total score at 12 weeks at 5% significance level, based on an SD of 4.7 in each arm and 20% attrition at 6 weeks. Analysis will be by intention to treat and pre defined in a statistical analysis plan Ethics and dissemination East of Scotland Research Ethics Service (EoSRES), 18/ES00042, obtained on 10 May 2018. The trial will allow us to determine effectiveness, safety, cost and acceptability of TTNS for bladder dysfunction in PWP. Results will be published in open access journals; lay reports will be posted to all participants and presented at conferences. Trial registration number ISRCTN12437878; Pre-results

Serotonin and Noradrenaline Reuptake Inhibitors Improve Micturition Control in Mice

Poor micturition control may cause profound distress, because proper voiding is mandatory for an active social life. Micturition results from the subtle interplay of central and peripheral components. It involves the coordination of autonomic and neuromuscular activity at the brainstem level, under the executive control of the prefrontal cortex. We tested the hypothe- sis that administration of molecules acting as reuptake inhibitors of serotonin, noradrenaline or both may exert a strong effect on the control of urine release, in a mouse model of overac- tive bladder. Mice were injected with cyclophosphamide (40 mg/kg), to increase micturition acts. Mice were then given one of four molecules: the serotonin reuptake inhibitor imipra- mine, its metabolite desipramine that acts on noradrenaline reuptake, the serotonin and nor- adrenaline reuptake inhibitor duloxetine or its active metabolite 4-hydroxy-duloxetine. Cyclophosphamide increased urine release without inducing overt toxicity or inflammation, except for increase in urothelium thickness. All the antidepressants were able to decrease the cyclophosphamide effects, as apparent from longer latency to the first micturition act, decreased number of urine spots and volume of released urine. These results suggest that serotonin and noradrenaline reuptake inhibitors exert a strong and effective modulatory ef- fect on the control of urine release and prompt to additional studies on their central effects on brain areas involved in the social and behavioral control of micturition

Making Rasch decisions: the use of Rasch analysis in the construction of preference based health related quality of life instruments

Objective: To set out the methodological process for using Rasch analysis alongside traditional psychometric methods in the development of a health state classification that is amenable to valuation. Methods: The overactive bladder questionnaire is used to illustrate a four step process for deriving a reduced health state classification from an existing nonpreference based health related quality of life instrument. Step I excludes items that do not meet the initial validation process and step II uses criteria based on Rasch analysis and psychometric testing to select the final items for the health state classification. In step III, item levels are examined and Rasch analysis is used to explore the possibility of reducing the number of item levels. Step IV repeats steps I to III on alternative data sets in order to validate the selection of items for the health state classification. Conclusions: The techniques described enable the construction of a health state classification amenable for valuation exercises that will allow the derivation of preference weights. Thus, the health related quality of life of patients with conditions, like overactive bladder, can be valued and quality adjustment weights such as quality adjusted life years derived.Rasch analysis; health related quality of life; condition specific measure; preference-based measures; overactive bladder syndrome

Bowel dysfunction after transposition of intestinal segments into the urinary tract : 8-year prospective cohort study

Purpose Bowel function may be disturbed after intestinal segments are transposed into the urinary tract to reconstruct or replace the bladder. In 1997, our group were the first to report major bowel dysfunction in a cohort of such patients: up to 42% of those who were asymptomatic preoperatively describing new bowel symptoms postoperatively including explosive diarrhoea, nocturnal diarrhoea, faecal urgency, faecal incontinence and flatus leakage . We now describe bowel symptoms in this same cohort eight years later (2005). Materials and Methods 116 patients were evaluable. Of the remaining 37 from the original report: 30 had died, five no longer wished to be involved, and two could not be traced. Patients were asked to complete postal questionnaires identical to those used in the first follow-up, assessing the severity of bowel symptoms and quality of life using two validated instruments. Responses were compared with those from the original study. The Nottingham Health Profile quality of life scores were also compared to age and sex matched norms. Results 96 (83%) completed eight-year follow-up questionnaires: 43 after ileal conduit diversion (Group 1), 17 after clam enterocystoplasty for overactive bladder (Group 2), 18 after reconstructed bladder for neurogenic bladder dysfunction (Group 3), and 18 with bladder replacement for non-neurogenic causes (Group 4). High prevalence rates of bowel symptoms persisted with no statistically significant differences between the two time points. Of those with symptoms in 2005, around 50% had reported similar symptoms in 1997. Clam enterocystoplasty patients (Group 2) still reported the highest prevalence (59%) of troublesome diarrhoea with one in two on regular anti-diarrhoeal medication. They also had high rates of faecal incontinence (47%), faecal urgency (41%) and nocturnal bowel movement (18%); with high proportions reporting a moderate or severe adverse effect on work (36%), social life (50%) and sex life (43%). High rates were also reported by neurogenic bladder dysfunction patients, including 50% with troublesome diarrhoea. This symptom was reported by 19% after ileal conduit and by 17% after bladder replacement for non-neurogenic causes. The impact of bowel symptoms on every-day activities and quality of life persisted, remaining most severe after clam enterocystoplasty, with 24% regretting undergoing the procedure because of subsequent bowel symptoms. Conclusions: After more than eight years, operations involving transposition of intestinal segments continue to be associated with high rates of bowel symptoms, which impact on everyday activities. These are particularly troublesome following enterocystoplasty for overactive bladder and bladder reconstruction for neurogenic bladder dysfunction. These risks should influence patient selection and potential patients should be warned prior to surgery