The Analysis Of Female OAB Patients’ Symptoms And Urodynamic Outcomes, And The Treatment Of Botulinum Toxin-A Injections For Female Refractory OAB

Backgroud:Overactive bladder is defined by ICS in 2012 as urgency with or without urgency urinary incontinence, usually accompanied by daytime frequency and nocturia, in the absence of UTI or other obvious pathology, large multinational population-based survey estimated the prevalence of overactive bladder (OAB) in Europe and Canada to be 12.8% in women and 10.8% in men。It is estimated the prevalence of OAB in China to be 5.9%in crowd over age of 18 and increase with age,over the age of 40, the prevalence of OAB up to 11.3%.OAB have a negative impact on patient’s life quality, social activities and career development. OAB has greater impact on people’s quality of life than diabetes,increasing the risk of falls and fractures, also may lead to mental problems such as depression, anxiety. OAB have a greater negative influence on female than male.A quarter female had complained of disturbing frequency, urgency or nocturia in life.20～30% of them were older than 55. Some studies reported OAB had a greater impact on women’s physical and psychological health than diabetes, causing lower satisfaction of sexual activity and marriage. In addition, OAB also increasedthe economic burden of patients and bring huge economic expenditure to the society.It cost 398 million Euro annually to cure OAB in Germany. The cost of curing OAB also increased rapidly in USA.OAB is a high prevalence and harmful disease to human and the society. A lot of research focused on the epidemiology, pathogenesis, and the effect of new treatments of OAB.But most studies have failed to press the different gender to OAB research, leading to obviously different results.There are obviously different symptoms between male and female OAB, DO is reported in 69% of men and 44% of women and urgency incontinence is reported in around 20% of men and 40% of women with overactive bladder symptoms. To avoid the big different even contradictory results,Some researcher suggested studies of OAB patients should be conducted by gender separately.Epidemiological survey has made a lot of study and evaluation on OAB patients’ symptoms.As epidemiological surveys were always conducted to large amount of crowds, they couldn’t make accurate diagnosis to a single patient. The data obtained is less valuable to clinical diagnosis and treatment. So it’s necessary to study confirmed female OAB patients’ clinical symptoms. It must be more valuable to clinic. Epidemiological survey has revealed morbidity of OAB is increased with age, but it needs further study to prove whether OAB patients’ symptoms exacerbate with age, and find the different symptoms between dry and wet OAB.OAB pathogenesis and etiology are not clear. Some researcher pointed out sensitive bladder and DO may related to OAB.Because OAB pathogenesis and etiology are not clear, there are many therapies but often difficult to cure. The main therapeutic principles is reducing symptoms, improving the patient’s quality of life. Treatments include behavioral therapy, oral drug therapy, sacralneuro modulation, and surgical. America Urology Assosiation recommend behavioral therapy should be associated with oral drug use (grade C recommendation). Oral drugs can alleviate OAB syndrom, however, many patients discontinue their use due to inadequate efficacy and/or intolerable side effects. Sacralneuro modulation has proved effective, but it is invasive, more expensive, and is difficult to use in clinical. Surgical treatment mainly is bladder expanding cystoplasty, due to the surgical trauma, irreversible, currently only applies to severe low compliance bladder, bladder capacity is small, harm to patients with upper tract function. Onabotulinum toxin A detrusor injection is a relatively safe, small trauma and effective treatment to refractory OAB. Chapple reports amulticentre, double-blind, randomised, placebo-controlled, phase 3 study enrolled patients with idiopathic OAB with> 3 urgency UI episodes over 3d and> 8 micturitions per day who were inadequately managed by anticholinergics. They found Onabotulinum toxin A significantly decreased UI episodes per day at week 12 Reductions from baseline in all other OAB symptoms were also significantly greater following onabotulinum toxin A compared with placebo.They conclude Onabotulinum toxin A 100u was well tolerated and demonstrated significant and clinically relevant improvements in all OAB symptoms, patient-reported benefit, and HRQOL in patients inadequately managed by anticholinergics. But the abotulinumtoxinA injection parts, dose and duration needs further study. The present study, there is no valid evidence to prove that onabotulinumtoxinA in which parts of the bladder injection can get the best treatment effect. Schurch indicates that the trigone should be spared because trigone injection can lead to bladder ureter reflux. But the other researchers report trigone injection should not cause bladder ureter reflux, most of the sensory nerve endings and bladder afferent nerve in the trigon, trigon injection will help to alleviate the symptoms of urinary frequency, urgency.Aims:The aim of our study is to record symptoms and characteristics of urine dynamics test, analysis the constituent ratio of them, patients were grouped by severity. Cases were divided into two groups by age, UUI and DO, Observed if there were difference in symptoms and characteristics of urine dynamics test between different groups. In order to provide evidence to choose a better clinic therapy.Refractory OAB patients,cases failed to respond to regular medical treatment,accepted Onabotulinum toxin A injection. Compare the different effects and safety in these two groups. In order to provides a new effective and safe method for female refractory OAB patients.Methods:K This was a prospective study. Inclusion criteria:a.Female,age≥18years old.b.Patients had frequency,urgency or nocturia with or without urgency urinary incontinence.c.course of disease were more than 3 months.d.Nerve system examination,urine regular test, urinary bacterial culture were normal.e. All patients had signed informed consent agreement.Exclusion criteria:a.Patients with lithiasis, urinary tract infection, tuberculosis, tumor or diabetes.b.patients with stress or mixed urinary incontinence.c.neurogenic bladder patient.d.pregnant women, e. patients had accepted OAB treatmentin last 2 months, such as behavior therapy, M receptor antagonis.f.Patients regarded as not suitable for this study.Recorded patients’age, course of the disease,3 days voiding diary,OABSS scores and QOL scores.109 cases were divided into two groups by age, UUI and DO respectively. Compared these parameters and found the difference of two groups.2、All patients underwent urodynamics studies, recorded maximum flow rate,voided volume, postvoid residual,volume at first desire,volume at urgent desire,and maximal cystometric capacity. Analysis patients’urodynamics characteristic.109 cases were divided into two groups by age, UUI and DO respectively. Compared urodynamics characteristicand found the difference of two groups.3-,40 women among 18 to 60 years old with refractory OAB were recruited from October 2012 to October 2014 in Foshan Women and Children hospital. Inclusion criteria:a.Female,age≥18years old.b.Patients had frequency,urgency or nocturia with or without urgency urinary incontinence. c. course of disease were more than 3 months. d. Patients were not satisfied with medicine and other regular treatment, or were nor tolerant to medicine side-effect.e.All patients had signed informed consent agreement.Exclusion criteria:a. Average urine volume>200ml or urinated less than 8 times in 24hours. b.Urine flow rate<15ml/s or residual urine volume>50ml.c.Patients with lithiasis, urinary tract infection, tuberculosis, tumor. d.Patients with stress or mixed urinary incontinence.e. Neurogenic bladder patient, f. Pregnant women, breast feeding women or preparing to be pregnant. g. Patients had accepted M receptor antagonist in last 2 months. h.Allergic to Onabotulinum toxin A. i. Patients with gastric retention, myasthenia gravis,or severe ulcerative colitis, j. Patients who were taking oral anticoagulants or with hemorrhagic disease. k. Patients were accepting other medicine test.1. Patients regarded as not suitable for this study. These patients were failure response to initial therapy of behavioral modifications and antimuscarinics more than 3 months. All cases were randomly allocated to the detrusor injection group (Group A)and detrusor combined trigon injection group(Group B).Patients accepted treatment via cystoscopy in condition of continuous epidural anesthesia. 100u OnabotulinumtoxinA was diluted into 30 ml sodium chloride, injected to 30 different sites of bladder,lml per site. Injection parts of group A patients were top, side wall and back wall of bladderexcluding the trigone, while group B patients including trigone injection 10ml solely, avoiding bilateral ureteral orifice and bladder neck injection.Evaluations were performed before treatment as baseline, and at the time of 1 and 3 month after treatment. Evaluations included 3 days’bladder diary recording frequence of daytime voiding,nocturia,urgency and urge, Overactive Bladder Symptom Score (OABSS), quality of life(QOL), and urodynamic test.4、Data was analyzed by SPSS 19.0 Measurement data were recorded as MEAN±TD. The statistic procedures of independent samplest tests were employed to analyze data of the two groups. Enumeration data were analyzed by rank sum test.Results:1、Clinical symptoms analysis109 female OAB patients were recruited in one hospital from December 2012 to December 2014.75cases were younger than thirty-nine,34 cases were older than forty.Frequency were the most popular urinary symptoms.58.7% of patients urinated more than 15 times each day.56% of patients had more than 5 times urgency a day.87.2%(95/109) of patients complained of nocturia; 53.2%(58/109) of patients had to wake up more than three times to void.21.1%(23/109) of patients complained of urge incontinence;OABSS scores ranged from 4 to 15 points, the average scores were 8.92±2.42,9 cases (8.3%)ranged from 0 to 5 points,87 cases (79.8%) ranged from 6 to 11 points,13 cases (11.9%) were more than 12 points. QOL scores range from 4 to 6, average scores were 5.29±0.74,18 cases (16.5%) ranged from 0 to 4,41cases (37.6%) scored 5, and 50 cases (45.9%) scored 6. Patients were divided into two groups by age. Compared their clinical symptoms, OABSS and QOL scores. Elderly group had a higher UUI incidence and OABSS scores. If patients were grouped by DO, patients with DO were obviously older and had a higher OABSS scores, QOL scores than patients without DO.2> Urodynamic analysisQmax ranged from 3-40ml/s in these 109 cases,the average Qmax were 13.05±6.54ml/s,77cases (70.6%)≤15ml/s,26cases (23.9%) 15～25ml/s,6 cases (5.5%)>25ml/s.Voiding volume ranged from 100-420ml,the average voiding volume were 185.90±85.59 ml,50cases (45.9%)<150ml,34cases(31.2%)ranged from 150-250ml,25cases (22.9%)>250ml;PVR ranged from 0 to 80ml,the average PVR were 19.91±31.16ml,volume at first desire (VFD) range from 40 to 230ml,The average of VFD were 92.32±45.11ml,24 (22%) cases VFD<50ml,54cases (49.5%) 51～100ml,31 cases (28.4%) VFD>101 ml; volume at urgent desire(VUD)range from 80 to 350ml,The average of VUD were 168.14±63.66 ml,153 cases (48.6%) ≤150m,49 cases (45%) 151-250ml,7 cases (6.4%)>250ml. maximal capacity (MCC) ranged from 110 to 480ml,The average of MCC were 259.81±93.67ml.38cases (34.9%) MCC≤200ml,40cases (36.7%) MCC201-300ml,3 leases (28.4%) MCO 300ml.97cases (89%) without detrusor overactive(DO),12cases (11%) with detrusor overactive(DO).Patients were divided into 2groups by age,Group A>40 years old and Group B<40years old. Compared these parameters and we found group A had a higher DO incidence. If patients were grouped by UUI, patients with UUI had a higher DO incidence than patients without UUI.If patients were grouped by DO, patients with DO were older and had a higher OABSS scores, QOL scores, less voiding volume and maximal capacity than patients without DO.3、Onabotulinum toxin A therapeutic effect and safety analysisDetrusor injection group (group A) and detrusor combined trigon injection group (group B) general information:age, duration, weight, f test of variance showed equal variance, t test showed that indexes mentioned of two groups had no statistical difference, proved that the two groups were comparable.3.1 All index of group A cases at different time point(before treatment (baseline),1 month after treatment,3 month after treatment)were recorded, Compare index at different time point each other. There were significant improvement in frequency,Voiding volume、Urgency episodes、VFD、MCC、QOI、OABSS (P <0.05)3.2All index of group B cases at different time point(before treatment(baseline), 1 month after treatment,3month after treatment)were recorded, Compare index at different time point each other. There were significant improvement in frequency,Voided volume、Urgency episodes、VFD、MCC、QOL、OABSS (P <0.05)3.3Comparison Group A and B at the same time point after treatment:when compared 1 months s after treatment with the two group, group B were significant improvement in frequency,Voided volue、 Urgency episodes、VFD、MC、QOI、 OABSS, Compared among them were statistically significant differences.when compared 3 months s after treatment with the two group, group B were significant improvement in frequency,Voided volume、Urgency episodes、VFD、MC、QOL、 OABSS, Compared among them were statistically significant differences(P<0.05).4、Statistical analysis was performed by SPSS 19.0. For statistical analysis, QOL to MCC were analyzed by Two sample mean t test,P<0.05 was considered as statistically significant.Urgency,DO and urge incontinence were analyzed by rank test.Conclusions:Through the female OAB patients’ clinical symptoms and urodynamics research,we found OAB affects female’s quality of life,and with the age increasing, Women with OAB syndrome were more seriouse, DO also increased. Female patients with DO experienced a more significant impairment of their quality of life and have a greater degree of bladder dysfunction than those without it. Both Onabot A detrusor injection and detrusor combined trigon to treat refractory OAB obtained good effect in short term,Detrusor combined trigon injection’s curative effect was better. Detrusor combined trigon injection was a safe and effective treatment, which was suitable for wider clinical use.