Abstract Context Overactive bladder (OAB) treatment guidelines recommend antimuscarinics as first-line pharmacologic therapy. Mirabegron is a first-in-class β3-adrenoceptor agonist licensed for the ...treatment of OAB and has shown to be well tolerated and effective in the treatment of OAB symptoms. Objective To assess the relative efficacy and tolerability of OAB medications, specifically mirabegron 50 mg versus antimuscarinics in patients with OAB. Evidence acquisition A systematic literature search was performed on published peer-reviewed articles from 2000 to 2013. This review included randomised controlled trials (RCTs) studying changes in symptoms (micturition frequency, incontinence, and urgency urinary incontinence UUI episodes) and incidence of the most frequently reported adverse events (dry mouth, constipation) associated with current OAB medications. The following drugs were considered in addition to mirabegron: darifenacin, tolterodine immediate release (IR) and extended release (ER), oxybutynin IR/ER, trospium, solifenacin, and fesoterodine. Bayesian mixed treatment comparisons (MTCs) were performed for efficacy (micturition, incontinence, UUI) and tolerability (dry mouth, constipation, blurred vision). Evidence synthesis Overall, 44 RCTs involving 27 309 patients were included. The MTCs showed that mirabegron 50 mg was as efficacious as antimuscarinics in reducing the frequency of micturition incontinence and UUI episodes, with the exception of solifenacin 10 mg that was more efficacious than mirabegron 50 mg in improving micturition frequency and frequency of UUI. Mirabegron 50 mg had an incidence of dry mouth similar to placebo and significantly lower than all included antimuscarinics. Conclusions Mirabegron 50 mg had similar efficacy to most antimuscarinics and lower incidence of dry mouth, the most common adverse event reported with antimuscarinics and one of the main causes of discontinuation of treatment. Despite being a powerful tool for evidence-based health care evaluation, the Bayesian MTC method has limitations. Further head-to-head comparisons between mirabegron and antimuscarinics should be conducted to confirm our results.
Women with vasomotor symptoms (VMS) due to menopause frequently experience poor sleep quality. The Patient-Reported Outcomes Measurement Information System Sleep Disturbance - Short Form 8b (PROMIS ...SD-SF-8b) has been developed to assess sleep disturbance. The study objective was to use data from the fezolinetant SKYLIGHT 1 and 2 studies in individuals with VMS to assess the psychometric properties of the PROMIS SD-SF-8b. Individuals (aged greater than or equal to 40-less than or equal to65 years) with moderate-to-severe VMS (greater than or equal to 7 hot flashes/day) were enrolled. Besides PROMIS SD-SF-8b, eight other patient-reported outcome (PRO) measures were used for the psychometric evaluation. All the PRO assessments were completed at weeks 4 and 12 during the treatment period and most were completed at baseline. Psychometric analyses included factor analysis and reliability, construct validity, and sensitivity to change assessments. The within-patient threshold for a clinically meaningful change in sleep disturbance was derived. Overall, 1022 individuals were included from the SKYLIGHT 1 and 2 studies. Mean PROMIS SD-SF-8b total score at baseline was 26.80, which decreased to 22.68 at week 12, reflecting improved sleep disturbance. The confirmatory factor analysis supported the proposed PROMIS SD-SF-8b domain structure. Internal consistency was excellent, with Cronbach's alpha values of 0.915 and 0.935 and a McDonald's omega of 0.917. Item-to-item and item-total correlations were sufficient and moderate test-retest reliability was noted. The construct validity assessments showed that moderate Spearman rank correlations (r: 0.608 to 0.651) were observed between PROMIS SD-SF-8b total scores and measures of sleep disturbance and sleep-related impairment, and that significant differences were noted in the total scores across PRO categories. The responsiveness of PROMIS SD-SF-8b total scores was supported by the results from the correlations in change scores and comparisons of mean change scores by PRO categories. Statistically significant differences in mean scores were observed between responder and non-responder PRO groups. A PROMIS SD-SF-8b total score of 8 points was identified as the within-patient threshold to use to confirm a meaningful change in sleep disturbance. The psychometric properties of the PROMIS SD-SF-8b support its use to measure sleep disturbance in women with VMS due to menopause.
Purpose
We evaluated the impact of menopause-associated vasomotor symptoms (VMS) on sleep. We also sought to establish the content validity of Patient-Reported Outcomes Measurement Information System ...(PROMIS) short form Sleep-Related Impairment and Sleep Disturbance measures in postmenopausal women with moderate to severe VMS.
Methods
Cross-sectional, in-person, qualitative interviews were conducted in the United States (Texas, Illinois) and European Union (UK, France) with women aged 40–64 years experiencing moderate to severe VMS (≥35/wk). Main outcomes were impact of VMS on sleep based on concept elicitation and content validity of PROMIS Sleep-Related Impairment and Sleep Disturbance short forms via cognitive debriefing.
Results
Thirty-two women (US:
n
= 16; EU: n = 16) participated. A majority (US: 93.8%; EU: 93.8%) said VMS affected sleep; specifically, they had sleep interrupted by sweating or overheating and had difficulty returning to sleep. Sleep disturbance was the most bothersome aspect of VMS (US: 75%; EU: 50%). VMS-associated sleep disturbance affected next-day work productivity, mood, relationships, daily activities, concentration, social activities, and physical health. Participants found both PROMIS sleep measures relevant and easy to answer; the Sleep Disturbance measure was considered the most relevant. Participants had no difficulty remembering their experiences over the 7-day recall period and found the response options to be distinct.
Conclusion
VMS associated with menopause significantly interferes with sleep and next-day functioning (e.g., work productivity), supporting assessment of sleep outcomes in studies evaluating treatment of VMS. Women with moderate to severe VMS found that the PROMIS Sleep-Related Impairment and Sleep Disturbance short forms assessed constructs important to understanding sleep in the context of menopause-associated VMS.
COVID-19 pandemic has exaggerated the role of steroids in the standard of care despite minimum direct evidence of their efficacy in COVID-19 patients and their well-known adverse effects. The ...literature abounds on the side effects of steroids affecting different organ systems of the body. COVID-19 patients, who are on long-term steroids, are more susceptible to their adverse effects. We, herein, briefly review the potential uses and the adverse effects of steroids on different organ systems of the body. Key Words: Steroids, COVID-19, Adverse effects.
Objective:
To compare the efficacy and safety of mirabegron 50 mg and solifenacin 5 mg in overactive bladder (OAB) patients dissatisfied with previous antimuscarinic treatment due to lack of ...efficacy.
Patients and methods:
This randomized, double-blind, phase IIIb, noninferiority study, enrolled male and female patients aged ⩾18 years old, with symptoms of OAB for ⩾3 months, who were dissatisfied with their previous antimuscarinic drug due to lack of efficacy. A total of 1887 patients were randomized to receive mirabegron 50 mg (n = 943) or solifenacin 5 mg (n = 944) daily for 12 weeks. The primary efficacy endpoint was change from baseline to end of treatment in mean number of micturitions/24 h. Noninferiority was confirmed if the lower limit of the two-sided 95% confidence interval (CI) for the treatment difference between solifenacin and mirabegron was > −0.20. Secondary efficacy endpoints, which included change from baseline in mean number of incontinence episodes/24 h, urgency incontinence episodes/24 h, urgency episodes (grade 3 or 4)/24 h and nocturia episodes/24 h, were analyzed using analysis of covariance.
Results:
For the primary endpoint, adjusted mean treatment difference (95% CI) in mean number of micturitions/24 h was −0.18 (−0.42, 0.06) and therefore noninferiority of mirabegron to solifenacin was not demonstrated. Both treatments demonstrated clinically meaningful reductions in efficacy variables and were well tolerated, with a lower incidence of dry mouth with mirabegron.
Conclusions:
Noninferiority of mirabegron compared with solifenacin for reduction in micturition frequency could not be demonstrated in this population of OAB patients who were dissatisfied with previous antimuscarinic therapy due to lack of efficacy. Both mirabegron and solifenacin improved key OAB symptoms with no statistically significant differences observed between the two treatments. Both drugs were well tolerated.
Background:
Oral pharmacotherapies to treat overactive bladder (OAB) are used less in men despite a similar prevalence of storage symptoms as women. The efficacy and safety of once-daily mirabegron ...50 mg was evaluated in male OAB patients from five phase III studies that included placebo or antimuscarinic (tolterodine ER 4 mg or solifenacin 5 mg) as a comparator.
Methods:
Three pooled 12-week placebo-controlled studies (mirabegron 50 mg versus placebo) and one 12-week non-inferiority phase IIIb study (BEYOND; mirabegron 50 mg versus solifenacin 5 mg) were used for efficacy (daily micturition frequency, urgency and incontinence episodes) and safety analyses. An additional 52-week active-controlled phase III safety study (mirabegron 50 mg versus tolterodine ER 4 mg) was included in the safety analysis. Male patients aged ⩾18 years with OAB for ⩾3 months were included in the analyses. Patients may also have a history of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH)/benign prostatic enlargement (BPE) or concomitant use of α1-blockers.
Results:
In the pooled studies, mirabegron 50 mg demonstrated superiority versus placebo (treatment difference: −0.37 95% confidence interval (CI): −0.74, −0.01) for reducing micturition frequency; improvements in urgency and incontinence were not significantly different between mirabegron 50 mg and placebo. In BEYOND, mirabegron 50 mg was comparable with solifenacin 5 mg for reducing micturition frequency, urgency, and incontinence episodes. Mirabegron was well tolerated at 12 and 52 weeks and overall treatment-emergent adverse events (AEs) were similar to those with placebo.
Conclusions:
In a male OAB population with or without LUTS associated with BPH/BPE, mirabegron 50 mg provided similar improvements in urgency, frequency, and incontinence as solifenacin 5 mg, and is a well-tolerated alternative to antimuscarinics. In the three pooled 12-week studies, significant differences were not seen for urgency and incontinence versus placebo, although mirabegron 50 mg did demonstrate significant improvements versus placebo for frequency.
The aim of the present review article was to summarize the efficacy and tolerability for mirabegron 50 mg over 12 weeks and 1 year versus placebo (SCORPIO) or tolterodine ER 4 mg (SCORPIO and ...TAURUS). After a 2‐week placebo run‐in, adults with overactive bladder symptoms for ≥3 months were randomized if, during a 3‐day micturition diary period before baseline, they had an average of ≥8 micturitions/24 h and ≥3 urgency episodes. Efficacy end‐points were change from baseline to each study visit and final visit in incontinence, micturitions, volume voided/micturition, urgency incontinence, urgency (grades 3 or 4), level of urgency and nocturia. Additional secondary efficacy variables included patient‐reported outcomes. Safety variables included changes in treatment‐emergent adverse events and vital signs. For SCORPIO, statistically significant improvements from baseline in efficacy variables and patient‐reported outcomes were seen with mirabegron versus placebo from week 4, and were maintained over time. For TAURUS, numerical improvements in efficacy were evident from month 1, and were maintained throughout 12 months. Treatment‐emergent adverse events incidence was similar between groups, except for dry mouth, which was reported by fourfold (SCORPIO) and threefold (TAURUS) more patients taking tolterodine than mirabegron. Mirabegron 50 mg for 12 weeks was associated with statistically significant improvements in objective measures of efficacy and patient‐reported outcomes. At final visit, improvements with mirabegron 50 mg were statistically greater versus placebo. The efficacy profile of mirabegron 50 mg appears to be maintained over 12 months.
To determine the clinical outcome and mean length of hospital stay of paediatric patients with severe blunt traumatic head injury (THI) receiving 3% hypertonic saline (HTS) in the Emergency ...Department (ED).
This case series study was conducted at the Department of Emergency Medicine, Aga Khan University Hospital, Karachi, from 2014 to 2015 via chart review of 105 patients. Detailed history and clinical examination of all paediatric patients aged 2-16 years was recorded which included moderate to severe head injury as classified by the Glasgow Coma Scale (GCS) by the Brain Trauma Foundation. As per routine care after admission of such a patient, for resuscitation 3% HTS was administered. GCS was recorded at 6 hours and at the time of discharge.
Of the 105 patients, 76 (72.4%) were male and 29 (27.6%) were female, and the mean age was 61.6+45.9 months. Traumatic brain injury (TBI) was found moderate in 60 (57.1%) cases and severe in 45 (42.9%) of our patients as per the GCS. Six hours after resuscitation with 3% hypertonic saline, 45 (43%) patients normalised as per GCS, 39 (37%) patients had moderate TBI and 21 (20%) had severe TBI. Forty five patients had a hospital stay of 2-3 days. The GCS improved after resuscitation with 3% hypertonic saline in emergency department, with a mean length of stay of 4.6+3.9 and 12.6+10.7 days in moderate and severe head injury respectively with a P value of <0.001, and was normal in 94 (89.5%) patients at the time of discharge.
Paediatric patients with TBI receiving 3% hypertonic saline results in improved GCS and a decrease in the length of hospital stay.
Abstract Context Debate exists on overactive bladder (OAB) treatment-response assessment in clinical trials and the nature and shortcomings of the different endpoints used in OAB clinical research. ...Objective To evaluate current evidence and tools that measure OAB treatment response in clinical trials and to inform the development of a new multidimensional patient-reported outcome (PRO) that could be used as a primary endpoint in OAB trials. Evidence acquisition We conducted a narrative review of OAB literature available in the PubMed database published between January 1, 2004 and June 30, 2015. Eighty articles were selected for full text review. Evidence synthesis The assessment of treatment outcomes in OAB is challenging due to the heterogeneity of symptoms and reliance on PROs. OAB studies report a high level of placebo effect and the placebo response is poorly understood. We found significant correlations between PRO measures and bladder diaries. There is evidence of several issues with the bladder diary: burden, over/underestimation, recall period, and lack of validation. Trials for other conditions—interstitial cystitis, benign prostatic hyperplasia, headache, and restless legs syndrome—have used symptom scales rather than diaries to measure treatment outcomes and some now incorporate PRO measures as primary, coprimary, and secondary endpoints. The International Consultation on Incontinence Research Society recommends evaluation of satisfaction, symptoms, health-related quality of life, and adverse events. Conclusions There is strong evidence of the shortcomings in current approaches to measuring OAB outcomes in clinical trials and recognition that a new simpler approach which incorporates symptom and health-related quality of life assessment could provide a more comprehensive, standardized approach to OAB assessment. Patient summary Overactive bladder is a urinary syndrome. Individuals experience different symptoms to varying degrees, which poses difficulties in accurately measuring the effect of treatment. This review found evidence and recommendations that propose a simpler but more comprehensive way to measure treatment outcomes.
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