Efficacy and safety of mirabegron for the treatment of neurogenic detrusor overactivity resulting from traumatic spinal cord injury: A prospective study.

OBJECTIVE: To assess the clinical, urodynamic efficacy, and safety of mirabegron in patients with neurogenic detrusor overactivity (NDO) consequent to traumatic spinal cord injury (SCI). METHODS: This prospective cohort study was performed between January 2018 and July 2019 and included adult patients with stable traumatic suprasacral SCI, performing clean intermittent catheterization (CIC), and demonstrating NDO on urodynamic study (UDS). A 3-day bladder diary was made at the baseline after which all patients were started on Mirabegron 50 mg. They were followed up at 6 weeks with a repeat bladder diary and UDS which were compared with those at the baseline. RESULTS: A total of 30 patients (4 females, 26 males, mean age: 30.07 years) were included. After 6 weeks of treatment, 5 out of the 29 incontinent patients became completely dry. The mean frequency of CIC decreased from 6.63 at the baseline to 5.37 at 6 weeks (p = .002), the mean CIC volume increased from 275 ml to 341 ml (p = .0002), the mean number of incontinence episodes in between CIC reduced from 3.97 to 2.27 (p < .0001) and time from CIC to leakage increased from 1.73 h to 2.75 h (p < .0001). The mean cystometric capacity increased from 348 ml to 406 ml (p = .008) and the maximum amplitude of NDO decreased from 54 cm H2 O to 41 cm H2 O (p = .005) at 6 weeks. Only two patients reported new onset dry mouth. No major adverse events were noted and none discontinued treatment. CONCLUSION: Mirabegron is efficacious and safe in patients with NDO consequent to traumatic SCI.

"Mesh free" autologous transobturator mid urethral sling placement for predominant stress urinary incontinence: A pilot study.

AIMS: To assess the efficacy and safety of autologous mid-urethral sling (MUS) in women with predominant stress urinary incontinence (SUI). MATERIALS AND METHODS: This prospective cohort study included adult women with predominant SUI seen in our urology clinic between January 2018 and March 2019. Patients with: negative cough stress test, history of prior incontinence surgery, urogenital malignancy, pelvic radiation, neurological disease, body mass index more than 40 kg/m2 , the presence of more than Stage I pelvic organ prolapse, active urinary tract infection, maximum flow rate less than 15 ml/sec, postvoid residual urine more than 100 ml, abdominal leak point pressure less than 60 cm of H2 O, and pregnant women were excluded. Eligible patients underwent a transobturator MUS procedure using rectus fascia as a sling. Before the procedure, patients filled the International Consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptom (ICIQ-FLUTS) and the Female Sexual Function Index (FSFI) questionnaire. Urinary outcomes were assessed at 3- and 12-months while sexual outcomes were assessed at 12-months. RESULTS: Thirty patients with median age of 44.5 years were included. All patients had a negative cough stress test during follow up. A significant improvement was noted in the ICIQ-FLUTS scale, bother scale, filling and incontinence subscales at 3 and 12 month follow-up. A significant improvement was also noted in the FSFI full scale score and FSFI domains of mean sexual desire, arousal and lubrication at 12 months follow-up. Two patients developed voiding dysfunction requiring urethral dilatation. CONCLUSION: Autologous transobturator MUS surgery appears to be safe and efficacious in the short term. More research is needed to clarify its role in the surgical management of SUI in women.

Semisolid matrix-filled hard gelatin capsules for rapid dissolution of amlodipine besilate: Development and assessment.

The objective of the study was to prepare semisolid capsules (SSCs) of poorly water-soluble drug amlodipine besilate (AB) using a combination of technologies involving solid dispersion (SD) preparation and converting it into semisolid matrix filled in hard gelatin capsules (termed as SSCs) with the aim of reducing lag time in drug release and to improve the dissolution rate. AB is used for its anti-arrhythmic, anti-anginal, and anti-hypertensive activity. These are the emergency activities which should be treated as fast as possible like in the case of angina attack (heart attack). Any lag time that is generated due to its poor dissolution can add on in this emergency and that can be avoided by developing a readily dissolvable formulation: SDs of AB. SD of AB was prepared by fusion method using varying combinations of Poloxamer 407 and Plasdone S630. A total of nine batches (SD1-SD9) were characterized for the in vitro dissolution behavior in phosphate buffer pH7.4. SD8 with 95.8% cumulative drug release in 60 min, t 50% = 4.1 min and DE30 Min = 84.2% were selected for the development of the semisolid matrix. Differential scanning calorimetry of SD8 revealed molecular dispersion of AB and Plasdone S630 in Poloxamer 407. SD8 was then formulated as SSCs using gelucire 44/14 and PEG 400 as semisolid components and PEG 6000 as a suspending agent to achieve the reduction in lag time for drug release. A total of seven SSC formulations were prepared and evaluated for drug release. Formulation of SSC4 showed maximum cumulative drug release (CDR) of 98.9% within 20 min that was almost a threefold reduction in the time required to achieve similar CDR by SD of AB. Thus, SSCs present an excellent approach to enhance the dissolution as well as to reduce the lag time of dissolution for poor water-soluble drugs especially to those therapeutic classes that are intended for faster onset of action.