Dataset Information

The Impact of Gene Polymorphisms on the Success of Anticholinergic Treatment in Children with Overactive Bladder.

ABSTRACT:

Aim

To determine the impact of gene polymorphisms on detrusor contraction-relaxation harmony in children with lower urinary tract symptoms (LUTS).

Materials and methods

Toilet trained children older than 5 years of age with LUTS and normal neurological examination underwent videourodynamic study. The control group was composed of age matched children with no voiding complaints. The study group who filled out the voiding dysfunction symptom score before and after the treatment received standard oxybutynin treatment and was reevaluated 1 year after treatment. Genomic DNA was isolated from all patients and subjected to PCR for amplification. Genotyping of ARGHEF10, ROCK2, ADRB3, and CYP3A4 was carried out with Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP) method.

Results

34 (45%) and 42 (55%) patients were enrolled in the study and control group, respectively. ARGEF10 GG, ADRB3 TC, and CYP3A4 AG genotype patients displayed insignificant difference between pre- and posttreatment voiding dysfunction symptom score and bladder volumes.

Conclusions

The polymorphism of genes in the cholinergic pathway did not significantly differ clinical parameters. On the other hand, polymorphic patients in the adrenergic pathway seemed to suffer from clinical disappointment. For this reason, we think that the neglected adrenergic pathway could be a new therapeutic target for the treatment of anticholinergic resistant LUTS in children.

SUBMITTER: Gurocak S

PROVIDER: S-EPMC4488149 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

The Impact of Gene Polymorphisms on the Success of Anticholinergic Treatment in Children with Overactive Bladder.

Gurocak Serhat S Konac Ece E Ure Iyimser I Senol Cem C Onen Ilke Hacer IH Sozen Sinan S Menevse Adnan A

Disease markers 20150624

<h4>Aim</h4>To determine the impact of gene polymorphisms on detrusor contraction-relaxation harmony in children with lower urinary tract symptoms (LUTS).<h4>Materials and methods</h4>Toilet trained children older than 5 years of age with LUTS and normal neurological examination underwent videourodynamic study. The control group was composed of age matched children with no voiding complaints. The study group who filled out the voiding dysfunction symptom score before and after the treatment rece ...[more]

PMID: 26166934

Similar Datasets

Project description:OBJECTIVE:To determine the effectiveness of anticholinergic drugs for the treatment of overactive bladder syndrome. DESIGN:Systematic review of randomised controlled trials. DATA SOURCES:Published papers and abstracts. STUDY SELECTION:Randomised controlled trials with anticholinergic drug treatment in one arm and placebo in another. DATA EXTRACTION:Primary outcomes of interest were patient perceived cure or improvement in symptoms, differences in number of incontinent episodes and number of voids in 24 hours, and side effects. Secondary outcomes of interest were urodynamic measures of bladder function (volume at first contraction, maximum cystometric capacity, and residual volume) and adverse events. DATA SYNTHESIS:32 trials were included, totalling 6800 participants. Most trials were described as double blind but were variable in other aspects of quality. At the end of treatment, cure or improvement (relative risk 1.41, 95% confidence interval 1.29 to 1.54), differences in incontinent episodes in 24 hours (estimated mean difference 0.6, 0.4 to 0.8), number of voids in 24 hours (0.6, 0.4 to 0.8), maximum cystometric capacity (54 ml, 43 ml to 66 ml), and volume at first contraction (52 ml, 37 ml to 67 ml), were significantly in favour of anticholinergics (P<0.0001 for all). Anticholinergics were associated with significantly higher residual volumes (4 ml, 1 ml to 7 ml; P=0.02) and an increased rate of dry mouth (relative risk 2.56, 2.24 to 2.92; P<0.0001). Sensitivity analysis, although affected by small numbers of studies, showed little likelihood of an effect of age, sex, diagnosis, or choice of drug. CONCLUSIONS:Although statistically significant, the differences between anticholinergic drugs and placebo were small, apart from the increased rate of dry mouth in patients receiving active treatment. For many of the outcomes studied, the observed difference between anticholinergics and placebo may be of questionable clinical significance. None of these studies provided data on long term outcome.

Project description:BackgroundFew studies have addressed whether anticholinergic (AC) medications for overactive bladder (OAB) cause cognitive decline in individuals with existing cognitive impairment, and whether the APOE ε4 gene increases this risk.ObjectiveTo determine whether OAB AC use is associated with a clinically relevant change in cognitive measures among adults with normal and abnormal cognition.Design setting and participantsThis was a retrospective cohort study using data from the National Alzheimer's Coordinating Center. Patients were enrolled at specialized centers in the USA between 2005 and 2019. Patients with existing OAB AC use, missing APOE ε4 status, and confounding neurologic diagnoses were excluded. New users of an OAB AC were matched 1:1 to patients not taking an OAB AC using propensity scores.InterventionNew use of oxybutynin, tolterodine, solifenacin, trospium, darifenacin, or fesoterodine.Outcome measurements and statistical analysisThe outcome was a change in cognitive function, measured as a ≥1-point increase on the Clinical Dementia Rating (CDR) instrument or a ≥3-point decrease on the Mini-Mental State Examination (MMSE). Conditional logistic regression with odds ratios (ORs) was conducted. We also tested for APOE ε4 effect modification.Results and limitationsAmong 18 835 eligible patients, 782 matched pairs were identified. The most common OAB ACs were oxybutynin (38%) and tolterodine (23%). There was no significant increase in the risk of a clinically relevant cognitive decline among OAB AC users (CDR: OR 1.38, 95% confidence interval [CI] 0.93-2.05; p = 0.11, MMSE: OR 1.06, 95% CI 0.79-1.43; p = 0.70). There was no significant interaction between APOE ε4 status and OAB AC use for the CDR (p = 0.38) or MMSE (p = 0.95) outcomes. Users of oxybutynin or tolterodine had numerically higher odds of a change on the CDR test (OR 1.65, 95% CI 0.98-2.77) that was close to statistical significance (p = 0.06). Limitations include the inability to determine medication dose or duration, and residual confounding.ConclusionsOAB AC use was not associated with a significant change in cognitive function among individuals with normal and abnormal cognition. Further research is necessary to determine if oxybutynin and tolterodine are significantly more likely to cause cognitive decline.Patient summaryUse of a specific class of overactive bladder medication was not associated with negative changes in brain function among patients with either normal or abnormal function. A genetic risk factor for Alzheimer's disease did not predispose individuals to cognitive decline when taking these drugs. Two of the drugs (oxybutynin and tolterodine) may lead to a higher risk of cognitive decline in comparison to other drugs, and this needs further research.

Project description:IntroductionA prespecified pooled analysis of two placebo-controlled, phase 3 trials evaluated whether the number of prior anticholinergics used or reason for their discontinuation affected the treatment response to onabotulinumtoxinA 100U in overactive bladder (OAB) patients with urinary incontinence (UI).MethodsPatients with symptoms of OAB received intradetrusor injections of onabotulinumtoxinA 100U or placebo, sparing the trigone. Change from baseline at week 12 in UI episodes/day, proportion of patients reporting a positive response ('greatly improved' or 'improved') on the treatment benefit scale (TBS), micturition and urgency were evaluated by number of prior anticholinergics (1, 2 or ≥ 3) and reason for their discontinuation (insufficient efficacy or side effects). Adverse events (AE) were assessed.ResultsPatients had taken an average of 2.4 anticholinergics before study enrolment. OnabotulinumtoxinA reduced UI episodes/day from baseline vs. placebo, regardless of the number of prior anticholinergics (-2.82 vs. -1.52 for one prior anticholinergic; -2.58 vs. -0.58 for two prior anticholinergics; and -2.92 vs. -0.73 for three or more prior anticholinergics; all p < 0.001). The proportion of TBS responders was higher with onabotulinumtoxinA vs. placebo (69.0% vs. 37.2% for one prior anticholinergic; 58.8% vs. 24.8% for two prior anticholinergics and 56.4% vs. 22.5% for three or more prior anticholinergics; all p < 0.001). Similar results were observed regardless of the reason for discontinuation. OnabotulinumtoxinA reduced the episodes of urgency and frequency of micturition vs. placebo in all groups. AEs were well tolerated, with a comparable incidence in all groups.ConclusionIn patients with symptoms of OAB who were inadequately managed by one or more anticholinergics, onabotulinumtoxinA 100U provided significant and similar treatment benefit and safety profile regardless of the number of prior anticholinergics used or reason for inadequate management of OAB. ClinicalTrials.gov: NCT00910845, NCT00910520.

Project description:ObjectiveTo estimate the association between cumulative anticholinergic burden and falls and fractures in patients with overactive bladder (OAB).DesignA retrospective claims-based study (2007-2015) of patients with OAB; outcomes from a subset were contrasted to a non-OAB comparison.SettingUnited States, commercially and Medicare-insured population.Participants154 432 adults with OAB and 86 966 adults without OAB, mean age of 56 years, and 67.9% women.Main outcome measuresCumulative anticholinergic burden, a unitless value representing exposure over time, was estimated over the 12 months pre-index ('at baseline') and every 6 months post index. Burden was categorised as no burden (0), low burden (1-89), medium burden (90-499) or high burden (500+). Unadjusted rates of falls or fractures were estimated, and the increased risk associated with anticholinergic burden (measured at the closest 6-month interval prior to a fall or fracture) was assessed using a Cox proportional hazards model and a marginal structural model.ResultsMedian (IQR) baseline anticholinergic burden was 30 (0.0-314.0) and higher among older (≥65 years, 183 [3.0-713.0]) versus younger (<65 years, 13 [0.0-200.0]) adults. The unadjusted rate of falls or fractures over the period was 5.0 per 100 patient-years, ranging from 3.1 (95% CI 3.0-3.2) for those with no burden, to 7.4 (95% CI 7.1-7.6) for those with high burden at baseline. The adjusted risk of falls and fractures was greater with higher anticholinergic burden in the previous 6 months, with an HR of 1.2 (95% CI 1.2 to 1.3) for low burden versus no burden, to 1.4 (95% CI 1.3 to 1.4) for high versus no burden. Estimates from marginal structural models adjusting for time-varying covariates were lower but remained significantly higher with a higher anticholinergic burden. Rates of falls and fractures were approximately 40% higher among those with OAB (vs those without).ConclusionHigher levels of anticholinergic burden are associated with higher rates of falls and fractures, highlighting the importance of considering anticholinergic burden when treating patients with OAB.

Dataset Information

The Impact of Gene Polymorphisms on the Success of Anticholinergic Treatment in Children with Overactive Bladder.

Aim

Materials and methods

Results

Conclusions

Publications

The Impact of Gene Polymorphisms on the Success of Anticholinergic Treatment in Children with Overactive Bladder.

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