ABSTRACT
INTRODUCTION AND OBJECTIVE: Desmopressin is well accepted as first-line medical therapy for enuresis. If ineffective, combination therapy of desmopressin + oxybutynin or desmopressin + imipramine has been used. This study assessed the efficacy of adjunct therapy with either imipramine or oxybutynin in the management of enuresis patients who failed desmopressin treatment. STUDY DESIGN: A retrospective chart review of our database for patients with enuresis was performed. Patients who were prescribed desmopressin, oxybutynin, and imipramine over 14 years for enuresis were included. Two cohorts of patients were examined; group OXY was treated with desmopressin and oxybutynin, and group IMP received desmopressin and imipramine. Pretreatment measurement of Vancouver Symptom Scores (VSS) were used to compare groups using the VSS question "I wet my bed at night" where 4: every night, 3: 4-5 nights per week, 2: 1-2 nights per week, 1: 3-4 nights per month, and 0: never. International Children's Continence Society (ICCS) criteria for continence success was utilized to determine outcomes. RESULTS: 2521 patients prescribed one of the 3 medications were identified. Among them, 81 patients (mean age: 10.5 ± 2.8 years) received combination therapy. Of which, 55 were male and 26 female. Specifically, 58 were prescribed both desmopressin and imipramine (group IMP), 23 desmopressin and oxybutynin (group OXY), and 4 transitioned from OXY to IMP. Mean pretreatment VSS showed no difference between groups. Both groups experienced minimal drops in wet nights with desmopressin alone. A comparison revealed that group IMP reduced wet nights significantly more than group OXY (VSS wet night score 0.7 ± 1.2 vs. 2.3 ± 1.1 respectively, p < 0.0001). Non-intent-to-treat complete response rate was 68% vs 5% (OR = 42.5, p < 0.001) (IMP vs. OXY respectively). Intent-to-treat response rates were 58%. DISCUSSION: Although first-line desmopressin treatment for enuresis is effective, it does not work for all patients, and many parents and children desire nighttime dryness. Clinicians have combined desmopressin with oxybutynin or imipramine for improved results, but research comparing these modalities is scarce. Our study suggests that the desmopressin and imipramine combination is superior at reducing nights wet compared to desmopressin and oxybutynin, attributed to imipramine's probable central mechanism rather than its secondary anticholinergic properties. Limitations include a modest sample size, retrospective design, and subjective responses to the Vancouver questionnaire. CONCLUSION: A combination of desmopressin and imipramine was more effective in reducing wet nights and had a complete response rate that was 42.5 times greater than desmopressin and oxybutynin.
Subject(s)
Antidiuretic Agents , Deamino Arginine Vasopressin , Drug Therapy, Combination , Imipramine , Mandelic Acids , Nocturnal Enuresis , Humans , Mandelic Acids/administration & dosage , Mandelic Acids/therapeutic use , Deamino Arginine Vasopressin/administration & dosage , Deamino Arginine Vasopressin/therapeutic use , Retrospective Studies , Child , Male , Female , Imipramine/administration & dosage , Imipramine/therapeutic use , Nocturnal Enuresis/drug therapy , Antidiuretic Agents/administration & dosage , Antidiuretic Agents/therapeutic use , Adolescent , Treatment OutcomeABSTRACT
Existing therapies for neurogenic detrusor overactivity (NDO), i.e. oral anticholinergics and botulinum toxin injections, can be associated with serious adverse effects or are not always sufficiently effective. Therefore, there is a need for alternative safe and effective treatment options for NDO. Intravesical oxybutynin has been successfully used for several years as a prescription drug in adults and children with spinal cord injury and spina bifida. In 2019, VESOXX® (FARCO-PHARMA, Cologne, Germany) became the first registered intravesical oxybutynin product in Germany, which is indicated for the suppression of neurogenic detrusor overactivity (NDO) in children from 6 years of age and adults, who are managing bladder emptying by clean intermittent catheterisation (CIC), if they cannot be adequately managed by oral anticholinergic treatment due to lack of efficacy and/or intolerable side effects. Overall, there are limited data regarding therapy with intravesical oxybutynin, with the majority of publications being retrospective case series. To date, there are limited data on the efficacy and safety of the newly approved intravesical oxybutynin therapy (VESOXX®) in NDO patients. This noninterventional case series from daily routine treatment which evaluated the physician reports of 38 patients suggests that intravesical oxybutynin effectively improves maximum detrusor pressure (Pdet max) by decreasing it by 59% from 51.94â¯cm H2O⯱ 26.12 standard deviation (SD) to 21.07â¯cm H2O⯱ 17.32 SD (Pâ¯< 0.001, nâ¯= 34). Maximum bladder pressure (MBC) increased by 34% from 260.45â¯ml⯱ 200.26 SD to 348.45â¯ml⯱ 175.90 SD. Positive or similar effects compared to previous therapies were seen in bladder morphology, number of incontinence episodes, urinary tract infections and adverse drug effects. This case series demonstrates that intravesical oxybutynin is an important addition to current therapies for the treatment of NDO and it is also efficacious in the rare setting of other underlying diseases beyond spinal cord injury or spina bifida. The approved intravesical oxybutynin preparation VESOXX® may be a useful alternative for patients who do not respond to other therapies or suffered side effects.
Subject(s)
Mandelic Acids , Urinary Bladder, Neurogenic , Urinary Bladder, Overactive , Humans , Administration, Intravesical , Germany , Mandelic Acids/therapeutic use , Mandelic Acids/administration & dosage , Mandelic Acids/adverse effects , Muscarinic Antagonists/administration & dosage , Muscarinic Antagonists/therapeutic use , Muscarinic Antagonists/adverse effects , Treatment Outcome , Urinary Bladder, Neurogenic/drug therapy , Urinary Bladder, Overactive/drug therapy , Urological Agents/therapeutic use , Urological Agents/administration & dosage , Urological Agents/adverse effectsABSTRACT
OBJECTIVE: Summarize the evidence on drug therapies for obstructive sleep apnea. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. PubMed, Embase, Scopus, Web of Science, SciELO, LILACS, Scopus, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched on February 17th, 2023. A search strategy retrieved randomized clinical trials comparing the Apnea-Hypopnea Index (AHI) in pharmacotherapies. Studies were selected and data was extracted by two authors independently. The risk of bias was assessed using the Cochrane Risk of Bias tool. RevMan 5.4. was used for data synthesis. RESULTS: 4930 articles were obtained, 68 met inclusion criteria, and 29 studies (involving 11 drugs) were combined in a meta-analysis. Atomoxetine plus oxybutynin vs placebo in AHI mean difference of -7.71 (-10.59, -4.83) [Fixed, 95 % CI, I2 = 50 %, overall effect: Z = 5.25, p < 0.001]. Donepezil vs placebo in AHI mean difference of -8.56 (-15.78, -1.33) [Fixed, 95 % CI, I2 = 21 %, overall effect: Z = 2.32, p = 0.02]. Sodium oxybate vs placebo in AHI mean difference of -5.50 (-9.28, -1.73) [Fixed, 95 % CI, I2 = 32 %, overall effect: Z = 2.86, p = 0.004]. Trazodone vs placebo in AHI mean difference of -12.75 (-21.30, -4.19) [Fixed, 95 % CI, I2 = 0 %, overall effect: Z = 2.92, p = 0.003]. CONCLUSION: The combination of noradrenergic and antimuscarinic drugs shows promising results. Identifying endotypes may be the key to future drug therapies for obstructive sleep apnea. Moreover, studies with longer follow-up assessing the safety and sustained effects of these treatments are needed. PROSPERO REGISTRATION NUMBER: CRD42022362639.
Subject(s)
Sleep Apnea, Obstructive , Sleep Apnea, Obstructive/drug therapy , Humans , Randomized Controlled Trials as Topic , Treatment Outcome , Atomoxetine Hydrochloride/therapeutic use , Mandelic Acids/therapeutic useABSTRACT
BACKGROUND AND OBJECTIVE: There is a reported association between overactive bladder (OAB) treated with antimuscarinic drugs and an increased risk of a dementia diagnosis, although short-term data suggest that newer OAB antimuscarinics are cognitively safe. This study examined the cognitive safety of fesoterodine in older adults with mild cognitive impairment (MCI) and OAB. METHODS: This four-way randomised crossover study examined the cognitive effects of fesoterodine 4 and 8 mg and oxybutynin 5 mg b.i.d. compared with placebo. Older adult patients with OAB and MCI were included. Treatment and washout periods were of 1-week duration, to reach steady-state drug levels. The primary outcome was continuity of attention at 1 and 4 h after the dose. The secondary outcomes included other cognitive domains, change in Montreal Cognitive Assessment score, and alertness. KEY FINDINGS AND LIMITATIONS: Twenty-three patients completed the study (16 females and seven males). For the primary outcome, at 1 h after the dose, a trend towards worsening of continuity of attention was observed for fesoterodine 4 mg (p = 0.09) compared with placebo. At 4 h after the dose, a nonstatistically significant trend towards improvement compared with placebo was observed in the fesoterodine 4 mg group (p = 0.0633) compared with placebo. No differences were observed in any other treatment group at either time point. Apart from quality of working memory, associated with a statistically significant improvement with fesoterodine 4 mg, there was no difference in any comparison for other secondary outcomes. CONCLUSIONS: Exposure to steady-state dosing of fesoterodine 4 and 8 mg or oxybutynin 5 mg b.i.d. was not associated with any detectable effect on cognitive function using a sensitive battery of cognitive tests in a group of older adult patients with MCI and OAB. PATIENT SUMMARY: In this report, we investigated whether the medication fesoterodine, a member of a family of drugs called anticholinergics, commonly used for the treatment of a condition called overactive bladder that leads to accidental leakage of urine, affected the memory function of older adults with mild memory impairment. These people might be more sensitive to memory side effects. We found that at the doses most used by doctors, the drug had no effect on any of the memory functions we tested.
Subject(s)
Benzhydryl Compounds , Cognition , Cognitive Dysfunction , Cross-Over Studies , Mandelic Acids , Muscarinic Antagonists , Urinary Bladder, Overactive , Humans , Urinary Bladder, Overactive/drug therapy , Benzhydryl Compounds/therapeutic use , Benzhydryl Compounds/administration & dosage , Benzhydryl Compounds/pharmacology , Female , Male , Aged , Cognitive Dysfunction/drug therapy , Double-Blind Method , Mandelic Acids/therapeutic use , Mandelic Acids/administration & dosage , Muscarinic Antagonists/administration & dosage , Muscarinic Antagonists/therapeutic use , Aged, 80 and over , Cognition/drug effects , Drug Administration ScheduleABSTRACT
Sleep hyperhidrosis is defined as profuse nocturnal sweating that disrupts sleep. Although the mechanism is unknown, some cases are secondary to hot flushes during the menopausal period, medical, mental and sleep disorders, and medication, while dysregulation of thermoregulation during sleep is suspected in primary cases. We present the case of a woman with severe primary sleep hyperhidrosis, occurring nightly for 23 years, which definitively resolved after brief treatment with oxybutynin (a muscarinic receptor-blocking anticholinergic). An ammoniacal odor in the sweat and a sensation of coldness on awakening during sweating episodes suggest that the mechanism of her night sweating was not an exacerbation of thermoregulation during the night but shares the mechanical properties of emotional/psychological sweating. This extreme case of sleep hyperhidrosis was treated with excellent efficacy and minimal side effects using oxybutynin, which could benefit other patients with nighttime discomfort. CITATION: Dias L, Martinot C, Vaillant G, Arnulf I. Severe night sweating treated by oxybutynin. J Clin Sleep Med. 2024;20(1):169-172.
Subject(s)
Hyperhidrosis , Sweating , Female , Humans , Hyperhidrosis/drug therapy , Hyperhidrosis/chemically induced , Muscarinic Antagonists/therapeutic use , Mandelic Acids/therapeutic useABSTRACT
PURPOSE: Pollakiuria is defined as a change in the pattern of daily urination. Students have mentioned wetting their pants at school as the third tragic event after the death of a parent or going blind. In this study, the effect of adding Montelukast to oxybutynin on the improvement of urinary symptoms of patients with pollakiuria was studied. MATERIALS AND METHODS: This study was a pilot clinical trial in which children with pollakiuria aged 3-18 years old were included. These children were randomly divided into two groups of intervention (Montelukast plus oxybutynin) and the control group (only oxybutynin). At the beginning and the end of the study (after 14 days), mothers were asked about the frequency of daily urination. Finally, the gathered data were compared between two groups. RESULTS: In the present study, 64 patients were examined in two intervention and control groups (32 in each group). The results revealed that although significant changes were observed in both groups before and after intervention, the average changes in the intervention group were significantly higher (p = 0.014). CONCLUSION: The results of this study showed that adding montelukast to oxybutynin has a significant decrease in frequency of daily urination in patients with pollakiuria, although further studies are recommended in this area.
Subject(s)
Muscarinic Antagonists , Urination , Humans , Child , Child, Preschool , Adolescent , Muscarinic Antagonists/pharmacology , Mandelic Acids/therapeutic use , Mandelic Acids/pharmacology , Double-Blind Method , Treatment OutcomeABSTRACT
Polymeric drug-releasing vaginal rings are useful for both local and systemic administration of drugs via the intravaginal route. Typically, they provide continuous sustained or controlled release of drug(s) over extended time periods, thereby avoiding overdose and improving adherence. This first-in-human study (EudraCT number: 2020-0050044-30) evaluated the pharmacokinetics, safety, and tolerability of a single dose of oxybutynin administered by a novel microprocessor-controlled vaginal ring (MedRing). Eight healthy female subjects received an electronically controlled single intravaginal dose of 3 mg oxybutynin hydrochloride (100 mg/mL) dissolved in 1:1 water/propylene glycol administered via MedRing. Following dosing, MedRing was kept in situ for up to 6 h. Blood samples were collected 1 h prior to oxybutynin dosing and subsequently at regular intervals post-dose for the assessment of plasma concentrations of oxybutynin and its active metabolite N-desethyloxybutynin. The results showed that MedRing efficiently administered oxybutynin via the intravaginal route, resulting in plasma oxybutynin levels comparable to orally administered oxybutynin. The mean ± standard deviation pharmacokinetic parameters for oxybutynin were Cmax 5.4 ± 2.7 ng/mL, AUCinf 34.9 ± 17.4 h ng/mL, t1/2 8.5 ± 3.5 h and for N-desethyloxybutynin were Cmax 3.9 ± 2.5 ng/mL, AUCinf 51.1 ± 43.1 h ng/mL, t1/2 7.7 ± 5.9 h. No serious adverse events were reported. The study demonstrates that intravaginal administration of oxybutynin hydrochloride using the MedRing device was well tolerated.
Subject(s)
Cholinergic Antagonists , Mandelic Acids , Humans , Female , Cholinergic Antagonists/adverse effects , Cross-Over Studies , Mandelic Acids/metabolism , Mandelic Acids/therapeutic useABSTRACT
BACKGROUND: Neurogenic detrusor overactivity (NDO) can damage the upper urinary tract leading to chronic renal impairment. Antimuscarinic therapy is used to improve urinary incontinence and protect the upper urinary tract in patients with NDO. OBJECTIVE: This study investigated safety and efficacy of fesoterodine, a muscarinic receptor antagonist, in 6â<18-year-old patients with NDO (NCT01557244). STUDY DESIGN: This open-label phase 3 study included 2 pediatric cohorts. Patients in Cohort 1 (bodyweight >25 kg) were randomized to fesoterodine 4 or 8 mg extended-release tablets or oxybutynin XL tablets administered over the 12-week active comparator-controlled phase. The safety extension phase evaluated fesoterodine 4 and 8 mg for a further 12 weeks, with patients in the oxybutynin arm allocated to fesoterodine 4 or 8 mg. Patients in Cohort 2 (bodyweight ≤25 kg) were randomized to fesoterodine 2 or 4 mg extended-release beads-in-capsule (BIC) administered over a 12-week efficacy phase and 12-week safety extension phase. Patients with stable neurologic disease and clinically or urodynamically proven NDO were included. The primary endpoint was change from baseline to Week 12 in maximum cystometric bladder capacity (MCC). Secondary efficacy endpoints included detrusor pressure at maximum bladder capacity, bladder volume at first involuntary detrusor contraction, bladder compliance, and incontinence episodes. Safety endpoints included adverse event incidence, and specific assessments of cognition, behavior and vision. The pharmacokinetics of 5-hydroxymethyl tolterodine (5-HMT; fesoterodine's active metabolite) was determined using population-pharmacokinetic analysis. RESULTS: In Cohort 1 (n = 124), fesoterodine 4 and 8 mg treatment resulted in significant increases from baseline in the primary endpoint of MCC at Week 12. In Cohort 2 (n = 57), fesoterodine 2 and 4 mg BIC treatment resulted in improvements in MCC from baseline. Fesoterodine 4 and 8 mg and fesoterodine 4 mg BIC led to improvements in some secondary efficacy endpoints. The most common treatment-related adverse reactions were gastrointestinal effects, such as dry mouth, which occurred more frequently with oxybutynin than fesoterodine. No detrimental effects on visual accommodation or acuity, or on cognitive function or behavior were observed. DISCUSSION: These safety and efficacy results are consistent with limited published data on fesoterodine treatment in pediatric populations with overactive bladder or NDO. Study limitations include the lack of placebo control and the small sample size, which limits the ability to make formal efficacy comparisons and detect rare adverse reactions. CONCLUSION: Fesoterodine has a favorable benefit-risk profile in 6â<18-year-old patients with NDO and may represent an additional option for pediatric NDO treatment.
Subject(s)
Urinary Bladder, Neurogenic , Urinary Bladder, Overactive , Urinary Incontinence , Humans , Child , Adolescent , Urinary Bladder, Overactive/complications , Treatment Outcome , Mandelic Acids/pharmacology , Mandelic Acids/therapeutic use , Urinary Incontinence/drug therapy , Muscarinic Antagonists/therapeutic use , Urodynamics/physiologyABSTRACT
Background: Enuresis, defined as involuntary nocturnal urination without any underlying organic disorder in a child expected to control urination, poses a common problem. This study evaluated the effectiveness of Tolterodine and Oxybutynin in children presenting with primary desmopressin-resistant enuresis. Materials and Methods: A randomized clinical trial was undertaken involving 68 participants aged between 5 and 16 years, all suffering from primary enuresis. These patients were randomly assigned to one of two treatment groups for a three-month period: Group 1, treated with Oxybutynin and Desmopressin, and Group 2, treated with Tolterodine and Desmopressin. Data on demographics, clinical and laboratory findings, and subjective responses to treatment were gathered. The response was measured based on the frequency of wetting incidents per night and week and compared with pre-treatment data. Results: Patients were divided into two groups (30 patients in Group 1 and 38 patients in Group 2). The mean age of the patients was 88.97±27.09 months. In the first treatment group, 6 out of 30 patients (20%) experienced a complete treatment response, as did 5 out of 38 patients (13.2%) in the second treatment group. This difference between the groups was not statistically significant. Seven patients (23%) in the Oxybutynin group and 13 patients (34%) in the Tolterodine group reported a lack of response to treatment, a difference that also lacked statistical significance. Conclusion: For patients resistant to Desmopressin, the addition of anticholinergic drugs elicited a significant response in over half of the patients. However, no benefit was observed in using either Oxybutynin or Tolterodine in the treatment of Desmopressin-resistant enuresis.
Subject(s)
Deamino Arginine Vasopressin , Mandelic Acids , Tolterodine Tartrate , Humans , Tolterodine Tartrate/therapeutic use , Child , Mandelic Acids/therapeutic use , Male , Female , Deamino Arginine Vasopressin/therapeutic use , Adolescent , Treatment Outcome , Child, Preschool , Nocturnal Enuresis/drug therapy , Muscarinic Antagonists/therapeutic use , Antidiuretic Agents/therapeutic use , Urological Agents/therapeutic use , Enuresis/drug therapy , Drug ResistanceABSTRACT
Background: Despite the therapeutic advancements of the last several decades, neurogenic bladder remains a significant source of morbidity for patients with a spinal pathology. Oxybutynin is a mainstay of treatment in pediatric populations despite significant side effects and highly variable bioavailability. Objectives: To characterize the use of oxybutynin in a cohort of pediatric patients with neurogenic bladder. Methods: Retrospective data were collected of dosing, drug interactions, and urodynamics parameters in the 100 consecutive patients in a spinal differences clinic who had an appointment between October 7, 2015, and December 30, 2015. In addition to descriptive statistics, a linear regression model of oxybutynin dose versus age and sex was developed to examine the impact of age on dosing variability. Results: One hundred patients (52% female) with a median age of 6.8 years were included. The median daily dose of oxybutynin was 0.36 mg/kg (interquartile range, 0.28-0.54 mg/kg). Of the 48 patients with a recent urodynamics study, 13 had a detrusor leak point pressure (DLPP) greater than the typical cutoff of 40 cm H2O, indicating a need for management escalation. However, of these 13 patients, 38% were already on or exceeding oxybutynin's maximum recommended dose. Conclusion: The wide dosing variability and high DLPPs despite maximal dosing indicate a need for further investigation of oxybutynin's bioavailability in this population compared to its side effects and clinical outcomes. If variability in response to the medication is due to differences in bioavailability, then a precision-dosing model based on patient genomics could be developed for oxybutynin.
Subject(s)
Spinal Cord Injuries , Urinary Bladder, Neurogenic , Child , Female , Humans , Male , Mandelic Acids/adverse effects , Mandelic Acids/therapeutic use , Retrospective Studies , Urinary Bladder, Neurogenic/drug therapy , UrodynamicsABSTRACT
BACKGROUND: The recent discovery that a combination of noradrenergic and antimuscarinic drugs improved upper airway muscle function during sleep and reduced OSA severity has revitalized interest in pharmacologic therapies for OSA. RESEARCH QUESTION: Would 1 week of reboxetine plus oxybutynin (Reb-Oxy) be effective on OSA severity? STUDY DESIGN AND METHODS: A randomized, placebo-controlled, double-blind, crossover trial was performed comparing 4 mg reboxetine plus 5 mg oxybutynin (Reb-Oxy) vs placebo in patients with OSA. After a baseline in-laboratory polysomnogram (PSG), patients underwent PSGs after 7 nights of Reb-Oxy and 7 nights of placebo to compare apnea-hypopnea index (AHI), which was the primary outcome. Response rate was based on the percentage of subjects with a ≥ 50% reduction in AHI from baseline. Secondary outcomes included Epworth Sleepiness Scale (ESS) score and psychomotor vigilance test (PVT) values. Home oximetry evaluated overnight oxygen desaturation index (ODI) throughout treatment. RESULTS: Sixteen subjects aged 57 [51-61] years (median [interquartile range]) with a BMI of 30 [26-36] kg/m2 completed the study. Reb-Oxy lowered AHI from 49 [35-57] events per hour at baseline to 18 [13-21] events per hour (59% median reduction) compared with 39 [29-48] events per hour (6% median reduction) with placebo (P < .001). Response rate for Reb-Oxy was 81% vs 13% for placebo (P < .001). Although ESS scores were not significantly lowered, PVT median reaction time decreased from 250 [239-312] ms at baseline to 223 [172-244] ms on Reb-Oxy vs 264 [217-284] ms on placebo (P < .001). Home oximetry illustrated acute and sustained improvement in the oxygen desaturation index on Reb-Oxy vs placebo. INTERPRETATION: The administration of Reb-Oxy greatly decreased OSA severity and increased vigilance. These results highlight potential possibilities for pharmacologic treatment of OSA. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04449133; URL: www.clinicaltrials.gov.
Subject(s)
Adrenergic Uptake Inhibitors/therapeutic use , Mandelic Acids/therapeutic use , Muscarinic Antagonists/therapeutic use , Reboxetine/therapeutic use , Sleep Apnea, Obstructive/drug therapy , Cross-Over Studies , Double-Blind Method , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Polysomnography , Severity of Illness Index , Sleep Apnea, Obstructive/blood , Sleep Apnea, Obstructive/physiopathology , Treatment OutcomeABSTRACT
Overactive bladder (OAB) is often treated with medications that block the cholinergic receptors in the bladder (known as anticholinergics). The effect of this medication class on cognition and risk of dementia has been increasingly studied over the past 40 years after initial studies suggested that the anticholinergic medication class could affect memory. Short-term randomized clinical trials demonstrated that the administration of the anticholinergic oxybutynin leads to impaired memory and attention, and large, population-based studies showed associations between several different anticholinergic medications and dementia. However, trials involving anticholinergics other than oxybutynin have not shown such substantial effects on short-term cognitive function. This discordance in results between short-term cognitive safety of OAB anticholinergics and the long-term increased dementia risk could be explained by the high proportion of patients using oxybutynin in the OAB subgroups of the dementia studies, or a study duration that was too short in the prospective clinical trials on cognition with other OAB anticholinergics. Notably, all studies must be interpreted in the context of potential confounding factors, such as when prodromal urinary symptoms associated with the early stages of dementia lead to an increase in OAB medication use, rather than the use of OAB medication causing dementia. In patients with potential risk factors for cognitive impairment, the cautious use of selected OAB anticholinergic agents with favourable physicochemical and pharmacokinetic properties and clinical trial evidence of cognitive safety might be appropriate.
Subject(s)
Cholinergic Antagonists/adverse effects , Cognition , Cognitive Dysfunction/chemically induced , Dementia/epidemiology , Urinary Bladder, Overactive/drug therapy , Benzhydryl Compounds/adverse effects , Benzhydryl Compounds/therapeutic use , Benzofurans/adverse effects , Benzofurans/therapeutic use , Cholinergic Antagonists/therapeutic use , Cognitive Dysfunction/epidemiology , Humans , Mandelic Acids/adverse effects , Mandelic Acids/therapeutic use , Prodromal Symptoms , Pyrrolidines/adverse effects , Pyrrolidines/therapeutic use , Risk Assessment , Risk Factors , Solifenacin Succinate/adverse effects , Solifenacin Succinate/therapeutic use , Tolterodine Tartrate/adverse effects , Tolterodine Tartrate/therapeutic useABSTRACT
Harlequin syndrome (HS) is a rare entity derived from the dysfunction of the sympathetic nervous system. It is characterised by unilateral facial flushing and sweating induced by exercise, heat and emotion. Most cases are primary with an unknown pathogenic mechanism. In these cases, the prognosis is favourable. Medical or surgical treatments are not usually required for idiopathic HS. However, symptomatic treatment may be indicated when symptoms affect the quality of life of patients. We present the case of a patient with idiopathic HS successfully treated with oxybutynin and propranolol. In this patient, a marked improvement in both hyperhidrosis and facial erythema was noted with this combined therapy. We consider it of interest to highlight the response of our patient to the treatment employed, which may be advantageous in future cases of this rare disorder.
Subject(s)
Autonomic Nervous System Diseases/diagnosis , Autonomic Nervous System Diseases/drug therapy , Flushing/diagnosis , Flushing/drug therapy , Hypohidrosis/diagnosis , Hypohidrosis/drug therapy , Mandelic Acids/therapeutic use , Parasympatholytics/therapeutic use , Propranolol/therapeutic use , Vasodilator Agents/therapeutic use , Female , Humans , Middle AgedABSTRACT
One recent study showed that atomoxetine-oxybutynin combination (AOC) use is effective in reducing obstructive sleep apnea (OSA) severity. We used a nationwide database to examine the association between AOC use and the risk of OSA incidence. This retrospective cohort study used Taiwan's National Health Insurance Research Database between the years 2000 and 2015. The patients who used atomoxetine or oxybutynin were included as an exposed cohort. The exposed and unexposed groups were selected in a ratio of 1:3 with sex, age, and index year matching. We used the multivariate Cox proportional regression model to evaluate the association between AOC use and the risk of an incident diagnosis of OSA. The incidence rates of OSA in the exposed cohort (N = 8940) and the unexposed cohort (N = 26,820), were 21.92 and 22.93 per 100,000 person-years, respectively. The adjusted hazard ratio of oxybutynin use only and AOC with a treatment duration of ≥ 366 days were 0.307 (95% CI 0.204-0.995, P = 0.045) and 0.299 (95% CI 0.102-0.933, P = 0.002), respectively. Long-term atomoxetine-oxybutynin combination therapy may be beneficial to reduce the risk of obstructive sleep apnea. Further studies to examine these mechanisms are warranted.
Subject(s)
Atomoxetine Hydrochloride/therapeutic use , Mandelic Acids/therapeutic use , Sleep Apnea, Obstructive/drug therapy , Adolescent , Adult , Aged , Child , Child, Preschool , Databases, Factual , Drug Discovery , Humans , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Risk Factors , Sleep Apnea, Obstructive/epidemiology , Sleep Apnea, Obstructive/pathology , Taiwan/epidemiology , Young AdultABSTRACT
OBJECTIVE: To determine the true failure rate of opioid free ureteroscopy (OF-URS) and rates of new-persistent opioid use utilizing a national prescription drug monitoring program. MATERIAL AND METHODS: We identified 239 patients utilizing our retrospective stone database who underwent OF-URS from Februrary 2018-March 2020. In Feb 2018, we initiated a OF-URS pathway (diclofenac, tamsulosin, acetaminophen, pyridium and oxybutynin). Patients who had a contraindication to NSAIDs were excluded from primary analyses. A prescription drug monitoring program was then utilized to determine the number of patients who failed OF-URS (defined as receipt of an opioid within 31 days of surgery) as well as rates of new-persistent opioid use (defined as receipt of opioid 91-180 days after surgery). All statistical analyses were performed using SAS 9.4. Tests were 2-sided and statistical significance was set at P<0.05. RESULTS: We found a OF-URS failure rate of 16.6% and 14.0% in the total and opioid naïve cohorts, respectively. Rates of new-persistent opioid use were 0.9% and 1.2%, respectively (lower than published expected rate of ~6% after URS with postoperative opioids). 91% of patients obtained opioid from alternative sources. Uni/multivariate analyses were performed for both cohorts. In the total cohort, benzodiazepine users had a lower risk of OF-URS failure on multivariate analysis. No variables were associated with OF-URS failure in the opioid naïve cohort. CONCLUSION: The true failure rate of OF-URS is higher than previously thought at 16.6% and 14.0%. However, efforts to reduce opioid prescriptions with OF-URS pathways have successfully reduced new-persistent opioid use.
Subject(s)
Analgesics, Non-Narcotic/therapeutic use , Analgesics, Opioid/therapeutic use , Drug Prescriptions/statistics & numerical data , Pain, Postoperative/drug therapy , Ureteroscopy , Acetaminophen/therapeutic use , Diclofenac/therapeutic use , Female , Humans , Kidney Calculi/surgery , Male , Mandelic Acids/therapeutic use , Middle Aged , Phenazopyridine/therapeutic use , Retrospective Studies , Tamsulosin/therapeutic useABSTRACT
PURPOSE: Williams-Beuren syndrome is a chromosomal disorder caused by a deletion at region 7q11.23. Lower urinary tract symptoms are highly prevalent and significantly affect quality of life. We assessed the long-term outcomes of lower urinary tract symptoms in children with Williams-Beuren syndrome. MATERIALS AND METHODS: From February 2001 to July 2016, 90 patients with Williams-Beuren syndrome were evaluated in our hospital, of whom 31 (20 boys) had at least 5 years of followup. Baseline evaluation included a history of lower urinary tract symptoms, frequency-volume chart and the impact on quality of life measured on a scale of 0 (delighted) to 6 (terrible). Pharmacological therapy with oxybutynin or doxazosin was offered to symptomatic patients. We present the outcome of lower urinary tract symptoms after 5 and 10 years of followup. RESULTS: At baseline 27 (87.1%) patients were symptomatic. Median duration of followup was 10 (range 6-13) years. Pharmacological therapy was started for 25 (92.6%) symptomatic patients at baseline, including oxybutynin for 19 (76.0%), doxazosin for 1 (4.0%) and a combination of the 2 agents for 5 (20.0%). Medical therapy was still in use by 61.2% after 5 years and 52.9% after 10 years (p=0.043). Median duration of pharmacological treatment was 7 (range 6-11) years. A significant improvement of lower urinary tract symptoms was observed over time, with 35.5% and 29.5% patients considered symptomatic after 5 years and 10 years, respectively (p <0.001). Quality of life was also markedly improved over time (p <0.001). CONCLUSIONS: This long-term study showed significant improvement of lower urinary tract symptoms in children and adolescents with Williams-Beuren syndrome over time. Long-term pharmacological treatment was needed in most patients.
Subject(s)
Lower Urinary Tract Symptoms/etiology , Williams Syndrome/complications , Adolescent , Adrenergic alpha-1 Receptor Antagonists/therapeutic use , Child , Doxazosin/therapeutic use , Female , Follow-Up Studies , Humans , Lower Urinary Tract Symptoms/drug therapy , Male , Mandelic Acids/therapeutic use , Time Factors , Urological Agents/therapeutic use , Williams Syndrome/drug therapyABSTRACT
OBJECTIVE: To examine the geographic and pharmacy-type variation in costs for generic benign prostatic hyperplasia (BPH) medications in order to improve drug price transparency and reduce health disparities. Medical therapy for BPH can be expensive, having significant implications for uninsured and underinsured patients. METHODS: We generated a 20% random sample of all pharmacies in Pennsylvania and queried each for the uninsured cash price of a 30-day prescription of tamsulosin 0.4mg daily, finasteride 5mg daily, oxybutynin immediate release 5mg TID and oxybutynin XL 10mg daily. Our primary objectives were to identify price variation based on pharmacy type (i.e., big chain and independent) and between geographic regions (predetermined by the Pennsylvania Health Care Cost Containment Council Database). We fit multivariable quantile regression models to test for an association between drug price and region after controlling for pharmacy type. RESULTS: Among 575 retail pharmacies contacted, 473 responded (82% response rate). The median cash price was significantly higher for big chain pharmacies than for independent pharmacies for tamsulosin ($66 vs. $15), finasteride ($68 vs. $15), oxybutynin immediate release ($49 vs. $35), and oxybutynin XL ($79 vs. $31) (all p < 0.05). When controlling for region, the median and 75th percentile price of all drugs was significantly higher for big chain pharmacies. When controlling for pharmacy type, regional variation was noted in all four drugs at the 75th percentile price and was greater for independent pharmacies. CONCLUSION: Compared to independent pharmacies, big chain pharmacies charged significantly more for generic BPH medications to uninsured patients. However, independent pharmacies demonstrated more regional variation in their pricing.
Subject(s)
Costs and Cost Analysis , Drugs, Generic/economics , Finasteride/economics , Mandelic Acids/economics , Prostatic Hyperplasia/economics , Tamsulosin/economics , Finasteride/therapeutic use , Humans , Male , Mandelic Acids/therapeutic use , Pennsylvania , Prostatic Hyperplasia/drug therapy , Tamsulosin/therapeutic useABSTRACT
INTRODUCTION: Although antimuscarinics form the first-line therapy in overactive bladder (OAB), little is known regarding antimuscarinic discontinuation among OAB patients in nursing homes. This study examined treatment patterns and predictors of antimuscarinic discontinuation among long-term nursing home (LTNH) residents with OAB. METHODS: The study cohort included LTNH residents (defined as residents staying ≥ 101 consecutive days) from the Minimum Data Set linked 2013-2015 Medicare claims data. Patients with OAB were defined by OAB-related claims and medication codes. Treatment patterns and discontinuation (medication gap ≥ 30 days) were characterized by examining OAB-specific antimuscarinics prescribed during LTNH stays. The Andersen Behavioral Model was used to identify predisposing, enabling and need factors that predict discontinuation. Kaplan-Meier curves and multivariable Cox proportional hazards regression model were used to assess the unadjusted and adjusted times to discontinuation, respectively, among different antimuscarinics. RESULTS: The mean age of the study cohort (n = 11,012) was 81.6 years (± 8.5), 74.6% were female, and 89.8% were non-Hispanic White. The mean duration of nursing home stay was 530.1 (± 268.4) days. The most commonly prescribed OAB-specific antimuscarinic was oxybutynin (69.8%). Overall, 66.5% of the study cohort discontinued the index antimuscarinic. Multivariable Cox PH regression analysis revealed that compared to LTNH residents who initiated treatment with oxybutynin, treatment discontinuation was lower with solifenacin or fesoterodin and discontinuation was more frequent when treatment was initiated with tolterodine, darifenacin or trospium compared with oxybutynin. In addition, several need factors (comorbidities, medication use and anticholinergic burden, etc.) were associated with antimuscarinic discontinuation. CONCLUSION: About two-thirds of LTNH residents with OAB discontinued their index antimuscarinic during their nursing home stay. There was significant variation in discontinuation based on the index antimuscarinic agent with lowest risk of discontiuation with solifenacin and fesoterodin. Concerted efforts to optimize antimuscarinic use are needed to improve the management of OAB in nursing homes.
Subject(s)
Benzofurans/therapeutic use , Mandelic Acids/therapeutic use , Muscarinic Antagonists/therapeutic use , Pyrrolidines/therapeutic use , Urinary Bladder, Overactive/drug therapy , Urological Agents/therapeutic use , Withholding Treatment/statistics & numerical data , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Male , Medicare/statistics & numerical data , Nursing Homes/statistics & numerical data , Proportional Hazards Models , Retrospective Studies , United StatesABSTRACT
BACKGROUND: Acne is an inflammatory disorder with a high global burden. It is common in adolescents and primarily affects sebaceous gland-rich areas. The clinical benefit of the topical acne treatments azelaic acid, salicylic acid, nicotinamide, sulphur, zinc, and alpha-hydroxy acid is unclear. OBJECTIVES: To assess the effects of topical treatments (azelaic acid, salicylic acid, nicotinamide, zinc, alpha-hydroxy acid, and sulphur) for acne. SEARCH METHODS: We searched the following databases up to May 2019: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers. SELECTION CRITERIA: Clinical randomised controlled trials of the six topical treatments compared with other topical treatments, placebo, or no treatment in people with acne. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Key outcomes included participants' global self-assessment of acne improvement (PGA), withdrawal for any reason, minor adverse events (assessed as total number of participants who experienced at least one minor adverse event), and quality of life. MAIN RESULTS: We included 49 trials (3880 reported participants) set in clinics, hospitals, research centres, and university settings in Europe, Asia, and the USA. The vast majority of participants had mild to moderate acne, were aged between 12 to 30 years (range: 10 to 45 years), and were female. Treatment lasted over eight weeks in 59% of the studies. Study duration ranged from three months to three years. We assessed 26 studies as being at high risk of bias in at least one domain, but most domains were at low or unclear risk of bias. We grouped outcome assessment into short-term (less than or equal to 4 weeks), medium-term (from 5 to 8 weeks), and long-term treatment (more than 8 weeks). The following results were measured at the end of treatment, which was mainly long-term for the PGA outcome and mixed length (medium-term mainly) for minor adverse events. Azelaic acid In terms of treatment response (PGA), azelaic acid is probably less effective than benzoyl peroxide (risk ratio (RR) 0.82, 95% confidence interval (CI) 0.72 to 0.95; 1 study, 351 participants), but there is probably little or no difference when comparing azelaic acid to tretinoin (RR 0.94, 95% CI 0.78 to 1.14; 1 study, 289 participants) (both moderate-quality evidence). There may be little or no difference in PGA when comparing azelaic acid to clindamycin (RR 1.13, 95% CI 0.92 to 1.38; 1 study, 229 participants; low-quality evidence), but we are uncertain whether there is a difference between azelaic acid and adapalene (1 study, 55 participants; very low-quality evidence). Low-quality evidence indicates there may be no differences in rates of withdrawal for any reason when comparing azelaic acid with benzoyl peroxide (RR 0.88, 95% CI 0.60 to 1.29; 1 study, 351 participants), clindamycin (RR 1.30, 95% CI 0.48 to 3.56; 2 studies, 329 participants), or tretinoin (RR 0.66, 95% CI 0.29 to 1.47; 2 studies, 309 participants), but we are uncertain whether there is a difference between azelaic acid and adapalene (1 study, 55 participants; very low-quality evidence). In terms of total minor adverse events, we are uncertain if there is a difference between azelaic acid compared to adapalene (1 study; 55 participants) or benzoyl peroxide (1 study, 30 participants) (both very low-quality evidence). There may be no difference when comparing azelaic acid to clindamycin (RR 1.50, 95% CI 0.67 to 3.35; 1 study, 100 participants; low-quality evidence). Total minor adverse events were not reported in the comparison of azelaic acid versus tretinoin, but individual application site reactions were reported, such as scaling. Salicylic acid For PGA, there may be little or no difference between salicylic acid and tretinoin (RR 1.00, 95% CI 0.92 to 1.09; 1 study, 46 participants; low-quality evidence); we are not certain whether there is a difference between salicylic acid and pyruvic acid (1 study, 86 participants; very low-quality evidence); and PGA was not measured in the comparison of salicylic acid versus benzoyl peroxide. There may be no difference between groups in withdrawals when comparing salicylic acid and pyruvic acid (RR 0.89, 95% CI 0.53 to 1.50; 1 study, 86 participants); when salicylic acid was compared to tretinoin, neither group had withdrawals (both based on low-quality evidence (2 studies, 74 participants)). We are uncertain whether there is a difference in withdrawals between salicylic acid and benzoyl peroxide (1 study, 41 participants; very low-quality evidence). For total minor adverse events, we are uncertain if there is any difference between salicylic acid and benzoyl peroxide (1 study, 41 participants) or tretinoin (2 studies, 74 participants) (both very low-quality evidence). This outcome was not reported for salicylic acid versus pyruvic acid, but individual application site reactions were reported, such as scaling and redness. Nicotinamide Four studies evaluated nicotinamide against clindamycin or erythromycin, but none measured PGA. Low-quality evidence showed there may be no difference in withdrawals between nicotinamide and clindamycin (RR 1.12, 95% CI 0.49 to 2.60; 3 studies, 216 participants) or erythromycin (RR 1.40, 95% CI 0.46 to 4.22; 1 study, 158 participants), or in total minor adverse events between nicotinamide and clindamycin (RR 1.20, 95% CI 0.73 to 1.99; 3 studies, 216 participants; low-quality evidence). Total minor adverse events were not reported in the nicotinamide versus erythromycin comparison. Alpha-hydroxy (fruit) acid There may be no difference in PGA when comparing glycolic acid peel to salicylic-mandelic acid peel (RR 1.06, 95% CI 0.88 to 1.26; 1 study, 40 participants; low-quality evidence), and we are uncertain if there is a difference in total minor adverse events due to very low-quality evidence (1 study, 44 participants). Neither group had withdrawals (2 studies, 84 participants; low-quality evidence). AUTHORS' CONCLUSIONS: Compared to benzoyl peroxide, azelaic acid probably leads to a worse treatment response, measured using PGA. When compared to tretinoin, azelaic acid probably makes little or no difference to treatment response. For other comparisons and outcomes the quality of evidence was low or very low. Risk of bias and imprecision limit our confidence in the evidence. We encourage the comparison of more methodologically robust head-to-head trials against commonly used active drugs.