**4. Conclusions**

Intravesical BoNT-A injections provided equally effective and durable therapeutic outcomes in both young and elderly patients ( ≥75 years old) with refractory OAB. The prevalence rates of common unfavorable outcomes were equal between the two age groups. For elderly patients receiving intravesical BoNT-A injection, female, lower bladder compliance, and higher PdetQmax were associated with postoperative UTI, whereas a history of DM and higher PdetQmax were associated with urinary retention postoperatively. A

thorough consultation for possible benefits and adverse events is mandatory, especially in elderly patients with certain risk factors.

#### **5. Materials and Methods**

We retrospectively reviewed patients with idiopathic OAB symptoms refractory to conventional medications who received intravesical injections of BoNT-A for the first time at a tertiary medical center in eastern Taiwan. All patients had persistent urgency urinary incontinence even with antimuscarinics, β3-adrenoceptor agonists, or a combination of both for more than three months. A multichannel urodynamic study, including cystometry and a pressure flow study, was performed preoperatively in accordance with the International Continence Society's good urodynamic practice recommendations [61] to confirm the presence of detrusor overactivity. All patients have been proven to be non-BOO by the video-urodynamic study before receiving the intravesical BoNT-A injections. Patients with underlying neurological factors that may cause neurogenic detrusor overactivity, or intrinsic sphincter deficiency were excluded from this study. Patients who were ≥75 years old while receiving the injections were classified into the elderly group, whereas the others belonged to the young group.

Baseline lower urinary tract function was assessed for each patient using uroflowmetry, PVR, and a multichannel urodynamic study before BoNT-A injection. Parameters including the VV, Qmax, CBC, and voiding efficiency were collected from the uroflowmetry. CBC was defined as the sum of VV and PVR, and voiding efficiency was defined as VV divided by CBC. For the multichannel urodynamic study, bladder sensations, compliance, and the presence of detrusor overactivity were recorded as the filling phase parameters, whereas PdetQmax, Qmax, VV, CBC, and PVR were recorded as the voiding phase parameters. BOO was defined as BOO index >40 for men [62], and as PdetQmax > 35 cmH2O for women [63]. Bladder sensations were further classified as the first sensation of filling, full sensation, and urge sensation, according to the patients' reports.

All patients were hospitalized and received intravesical injections of 100 units of Botox® (Allergan, Irvine, CA, USA), which is the standard dosage used to treat refractory OAB [26], under general anesthesia in the operating room. The injection method has been described previously [26]. Briefly, 10 mL normal saline was used to dilute each Botox vial. The injection needle was inserted into the posterior and lateral bladder walls under the guidance of rigid cystoscopy, and a total of 20 evenly distributed intradetrusor injections (0.5 mL for each injection) were performed while sparing the trigone area. A 14 Fr. urethral Foley catheter was placed and remained in place for one day after the Botox injection. Objective outcomes were assessed three months after the injections using uroflowmetry and PVR. Subjective treatment success and improvement of urge incontinence were reviewed according to the medical records at the out-patient department during serial follow-ups. As improvement of urinary incontinence and difficult urination might coexist after intravesical BoNT-A injection, patients might consider that they had unsuccessful treatment if they had severe difficulty in urination even though urinary incontinence had improved. Therefore, a subjective success was defined by having a Global Response Assessment (scoring from −3 to +3, indicating markedly worse to markedly improved after the treatment [64]) of +2 or +3. Underlying comorbidities and postoperative unfavorable outcomes, including a large PVR (defined as PVR >200 mL during the follow-up period), urinary retention, and UTI, were also collected from the patients' medical records. All patients were followed up regularly at the out-patient clinic with or without OAB medication, and repeat BoNT-A injections were performed if patients had recurrence of OAB symptoms and requested for injection, otherwise they were continuously treated with oral medications.

Statistical analyses were performed using SPSS Statistics for Windows, Version 17.0. Chicago: SPSS Inc. Continuous and categorical variables are expressed as mean ± standard deviation and as numbers and percentages, respectively. Statistical comparisons between groups were performed using the Mann–Whitney U test for continuous variables and the chi-square test for categorical variables. Fisher's exact test was applied when > 20% of the

expected frequencies were less than five. Comparisons between baseline and follow-up within-group differences were performed using the Wilcoxon signed-rank test. Age, gender, and variables demonstrating significant differences between patients with or without each unfavorable outcome were further analyzed with multivariate logistic regression analyses to identify factors associated with postoperative unfavorable outcomes in the elderly group. All statistical assessments were considered significant when the two-sided *p*-value was <0.05.

**Author Contributions:** Conceptualization, H.-C.K.; Data Curation, Y.-C.O. and H.-C.K.; Formal Analysis, Y.-C.O., Y.-L.K. and H.-C.K.; Investigation, Y.-C.O. and Y.-L.K.; Methodology, Y.-C.O., Y.-L.K., Y.-H.H. and K.-Y.W.; Project Administration, H.-C.K.; Resources, H.-C.K.; Supervision, H.-C.K.; Visualization, Y.-C.O., Y.-L.K., Y.-H.H. and K.-Y.W.; Writing—Original Draft, Y.-C.O.; Writing—Review and Editing, Y.-C.O., Y.-L.K. and H.-C.K. All authors have read and agreed to the published version of the manuscript.

**Funding:** The work was supported by grants from the National Cheng Kung University Hospital NCKUH-11206016 and Buddhist Tzu Chi Medical Foundation TCMF-SP-108-01 and TCMF-MP-110-03-01.

**Institutional Review Board Statement:** The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board of the Buddhist Tzu Chi General Hospital (IRB 104-23-A).

**Informed Consent Statement:** Patient informed consent was waived due to the retrospective study design.

**Data Availability Statement:** Data are available on request to the corresponding author.

**Conflicts of Interest:** The authors declare no conflict of interest.
