Treating moderate-to-severe menopausal vasomotor symptoms with fezolinetant: analysis of responders using pooled data from two phase 3 studies (SKYLIGHT 1 and 2).

OBJECTIVES: The aims of the study were to further characterize the efficacy of fezolinetant for the treatment of moderate-to-severe vasomotor symptoms (VMS) due to menopause using responder analysis and to investigate whether efficacy, not adjusted for placebo, resulted in clinically meaningful within-patient change. METHODS: This prespecified analysis used pooled data from two phase 3, randomized, double-blind, placebo-controlled studies (SKYLIGHT 1 and 2). Responders were those experiencing ≥50%, ≥75%, ≥90%, or 100% reduction in VMS frequency from baseline to weeks 4 and 12. Responder analysis was performed for patient-reported outcome (PRO) measures to evaluate participants achieving a clinically meaningful within-patient change (not placebo adjusted) at week 4 and 12 versus baseline. Single responders were based on outcomes of VMS frequency, Patient-Reported Outcomes Measurement Information System Sleep Disturbance-Short Form 8b Total Score, Menopause-Specific Quality of Life (MENQoL) Total Score, and MENQoL VMS Domain Score. Double and triple responder analyses combined VMS frequency plus one or more of the PRO. Patient Global Impression of Change VMS was deemed a suitable anchor measure for meaningful within-patient change in VMS frequency. RESULTS: A greater proportion of fezolinetant-treated versus placebo-treated participants had ≥50%, ≥75%, ≥90%, or 100% reduction in VMS frequency from baseline to weeks 4 and 12. A greater proportion of responders were observed in the fezolinetant groups versus placebo at week 12 in all four single responder analyses. In the double and triple responder analyses, odds ratios were supportive of a beneficial effect for both doses of fezolinetant versus placebo. CONCLUSIONS: Fezolinetant was associated with significantly higher within-patient clinically meaningful improvement in important PRO, including VMS frequency, PROMIS SD SF 8b Total Score, MENQoL Total Score, and MENQoL VMS Domain Score.

Psychometric Evaluation of the MENQOL Instrument in Women Experiencing Vasomotor Symptoms Associated with Menopause.

INTRODUCTION: Vasomotor symptoms (VMS) associated with menopause can negatively affect health-related quality of life (HRQoL). The Menopause-Specific Quality of Life (MENQOL) questionnaire has been developed to assess QOL specific to menopause. The objective of the current study was to assess the psychometric properties, sensitivity to change, and clinically meaningful within-patient change of the MENQOL using data from the fezolinetant SKYLIGHT 1 and 2 studies in individuals with VMS. METHODS: Individuals aged ≥ 40 to ≤ 65 years with moderate-to-severe VMS (≥ seven hot flashes/day) were enrolled. In addition to MENQOL, eight patient-reported outcome (PRO) measures were used for the psychometric evaluation. All 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 MENQOL was derived. RESULTS: In total, 1022 individuals were included from SKYLIGHT 1 and 2. Mean MENQOL total score at baseline was 4.30, improving to 3.16 at week 12. The confirmatory factor analysis supported established MENQOL domain structure, including the overall score. The internal consistency of the MENQOL overall and domain scores was supported using Cronbach's alpha and McDonald's omega, and MENQOL construct validity was supported for overall and domain scores. Item-to-item and item-total correlations were generally sufficient, and moderate test-retest reliability was noted. The scales against which construct validity and responsiveness for MENQOL domains were examined were moderately related to the MENQOL domains in general, providing additional support for acceptable measurement properties of MENQOL in this population. A reduction in MENQOL overall score of ≥ 0.9 points was identified as responding to treatment (a clinically important threshold). Thresholds of 2.0 points for the vasomotor domain and 0.9 for the psychosocial domain were estimated, in addition to distribution-based threshold estimates of 0.8 and 1.2 for the physical and sexual domains, respectively. CONCLUSIONS: The psychometric properties of the MENQOL overall and domain scores support use of this instrument to capture experiences among individuals with moderate-to-severe VMS associated with menopause and assess related endpoints in clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov identifiers NCT04003155 and NCT04003142.

Fezolinetant impact on health-related quality of life for vasomotor symptoms due to the menopause: Pooled data from SKYLIGHT 1 and SKYLIGHT 2 randomised controlled trials.

OBJECTIVE: To assess the effect of fezolinetant treatment on health-related quality of life using pooled data from SKYLIGHT 1 and 2 studies. DESIGN: Prespecified pooled analysis. SETTING: USA, Canada, Europe; 2019-2021. POPULATION: 1022 women aged ≥40 to ≤65 years with moderate-to-severe vasomotor symptoms (VMS; minimum average seven hot flushes/day), seeking treatment for VMS. METHODS: Women were randomised to 12-week double-blind treatment with once-daily placebo or fezolinetant 30 or 45 mg. Completers entered a 40-week, active extension (those receiving fezolinetant continued that dose; those receiving placebo re-randomised to fezolinetant received 30 or 45 mg). MAIN OUTCOME MEASURES: Mean changes from baseline to weeks 4 and 12 on Menopause-Specific Quality of Life (MENQoL) total and domain scores, Work Productivity and Activity Impairment questionnaire specific to VMS (WPAI-VMS) domain scores, Patient Global Impression of Change in VMS (PGI-C VMS); percentages achieving PGI-C VMS of 'much better' (PGI-C VMS responders). Mean reduction was estimated using mixed model repeated measures analysis of covariance. RESULTS: Fezolinetant 45 mg mean reduction over placebo in MENQoL total score was -0.57 (95% confidence interval [CI] -0.75 to -0.39) at week 4 and -0.47 (95% CI -0.66 to -0.28) at week 12. Reductions were similar for 30 mg. MENQoL domain scores were also reduced and WPAI-VMS scores improved. Twice as many women receiving fezolinetant reported VMS were 'much better' than placebo based on PGI-C VMS assessment. CONCLUSIONS: Fezolinetant treatment was associated with improvement in overall QoL, measured by MENQoL, and work productivity, measured by WPAI-VMS. A high proportion receiving fezolinetant felt VMS were 'much better' based on PGI-C VMS responder analysis.

Systematic review and network meta-analysis comparing the efficacy of fezolinetant with hormone and nonhormone therapies for treatment of vasomotor symptoms due to menopause.

IMPORTANCE: The neurokinin 3 receptor antagonist fezolinetant 45 mg/d significantly reduced frequency/severity of moderate to severe vasomotor symptoms (VMS) of menopause compared with placebo in two phase 3 randomized controlled trials. Its efficacy relative to available therapies is unknown. OBJECTIVE: We conducted a systematic review and Bayesian network meta-analysis to compare efficacy with fezolinetant 45 mg and hormone therapy (HT) and non-HT for VMS in postmenopausal women. EVIDENCE REVIEW: Using OvidSP, we systematically searched multiple databases for phase 3 or 4 randomized controlled trials in postmenopausal women with ≥7 moderate to severe VMS per day or ≥50 VMS per week published/presented in English through June 25, 2021. Mean change in frequency and severity of moderate to severe VMS from baseline to week 12 and proportion of women with ≥75% reduction in VMS frequency at week 12 were assessed using fixed-effect models. FINDINGS: The network meta-analysis included data from the pooled phase 3 fezolinetant trials plus 23 comparator publications across the outcomes analyzed (frequency, 19 [34 regimens]; severity, 6 [7 regimens]; ≥75% response, 9 [15 regimens]). Changes in VMS frequency did not differ significantly between fezolinetant 45 mg and any of the 27 HT regimens studied. Fezolinetant 45 mg reduced the frequency of moderate to severe VMS events per day significantly more than all non-HTs evaluated: paroxetine 7.5 mg (mean difference [95% credible interval {CrI}], 1.66 [0.63-2.71]), desvenlafaxine 50 to 200 mg (mean differences [95% CrI], 1.12 [0.10-2.13] to 2.16 [0.90-3.40]), and gabapentin ER 1800 mg (mean difference [95% CrI], 1.63 [0.48-2.81]), and significantly more than placebo (mean difference, 2.78 [95% CrI], 1.93-3.62]). Tibolone 2.5 mg (the only HT regimen evaluable for severity) significantly reduced VMS severity compared with fezolinetant 45 mg. Fezolinetant 45 mg significantly reduced VMS severity compared with desvenlafaxine 50 mg and placebo and did not differ significantly from higher desvenlafaxine doses or gabapentin ER 1800 mg. For ≥75% responder rates, fezolinetant 45 mg was less effective than tibolone 2.5 mg (not available in the United States) and conjugated estrogens 0.625 mg/bazedoxifene 20 mg (available only as 0.45 mg/20 mg in the United States), did not differ significantly from other non-HT regimens studied and was superior to desvenlafaxine 50 mg and placebo. CONCLUSIONS: The only HT regimens that showed significantly greater efficacy than fezolinetant 45 mg on any of the outcomes analyzed are not available in the United States. Fezolinetant 45 mg once daily was statistically significantly more effective than other non-HTs in reducing the frequency of moderate to severe VMS. RELEVANCE: These findings may inform decision making with regard to the individualized management of bothersome VMS due to menopause.

Psychometric evaluation of the PROMIS SD-SF-8b instrument in individuals experiencing vasomotor symptoms due to menopause.

BACKGROUND: 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. METHODS: Individuals (aged ≥ 40-≤65 years) with moderate-to-severe VMS (≥ 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. RESULTS: 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. CONCLUSIONS: The psychometric properties of the PROMIS SD-SF-8b support its use to measure sleep disturbance in women with VMS due to menopause. TRIAL REGISTRATION: ClinicalTrials.gov numbers: NCT04003155 and NCT04003142.

Paediatric Emergency Medicine: Reality, Expectation, Experience, and Need for Improvements from a Low- Income Settings.

Null.

Prevalence and quality-of-life burden of vasomotor symptoms associated with menopause: A European cross-sectional survey.

OBJECTIVES: To determine, in a European cohort, the prevalence and health-related quality-of-life (QOL) burden of moderate-to-severe vasomotor symptoms (VMS) in postmenopausal women, and among subgroups of women not taking hormone therapy (HT). STUDY DESIGN: Screening surveys were sent to a random sample of women aged 40-65 years; those meeting the inclusion criteria completed the full questionnaire. Women with successfully treated VMS or breast cancer or who were receiving HT for medical conditions were excluded. MAIN OUTCOME MEASURES: Frequency and duration of VMS, perceptions of menopause, seeking advice from a healthcare professional, treatment for VMS symptoms, perceptions of HT use, out-of-pocket costs, and other approaches to coping with menopause. The Menopause-Specific QOL (MENQOL) questionnaire and Work Productivity and Activity Impairment (WPAI) questionnaire were included. RESULTS: Of 11,452 women who completed the screening survey, 5178 were postmenopausal and 2035 completed the full questionnaire. Prevalence of moderate-to-severe VMS ranged from 31 % in France to 52 % in Italy. The majority were in the HT-caution or HT-averse group, despite being eligible for HT. Most common menopausal symptoms reported in the MENQOL were "feeling tired or worn out," with aching in muscles and joints reported as the most common symptom in Spain. Weight gain was the most bothersome symptom in all countries, except for Spain, where low backache was more bothersome. Hot flashes and night sweats had a greater impact on daily than on working activities, as measured by the WPAI. CONCLUSIONS: A high proportion of European women reported experiencing moderate-to-severe VMS, with associated symptoms influencing QOL.

Evaluation of the impact, treatment patterns, and patient and physician perceptions of vasomotor symptoms associated with menopause in Europe and the United States.

OBJECTIVES: This study elicited the views of physicians and patients with vasomotor symptoms (VMS) associated with menopause on the impact of VMS and treatment patterns/perceptions. STUDY DESIGN: Data from the Adelphi VMS Disease Specific Programme, a point-in-time survey conducted in 5 European countries and the United States in 2020, were used. Primary care providers (PCPs) and gynecologists seeing ≥3 patients/week with VMS associated with menopause completed a survey and chart review; their patients were invited to complete a survey and questionnaires. MAIN OUTCOME MEASURES: Physicians reported treatment patterns and patient-specific symptoms and treatment preferences. Patients described symptoms, impact of VMS, and treatment satisfaction. RESULTS: Participants included 115 PCPs and 118 gynecologists. Physicians reviewed the charts of 1816 patients, 854 of whom completed surveys. Moderate/severe impact of VMS on sleep, mood, quality of life, and work/study was reported by 35.8 %, 31.6 %, 23.6 %, and 15.4 % of women, respectively. Based on chart review, 64.8 % of women were currently prescribed treatment for VMS, most commonly hormone therapy (HT; 73.1 %), followed by selective serotonin or serotonin-norepinephrine reuptake inhibitors (31.3 %). Most women (57.3 %) with VMS were eligible for HT but averse to using it. Despite 91.4 % of physicians finding HT to be effective, 62.7 % agreed (slightly-strongly) that their patients are generally reluctant to use it. One-third of women were dissatisfied with VMS control. CONCLUSIONS: VMS can considerably impact daily life. Effective treatment options that are better accepted could potentially improve management of VMS and lead to better quality of life for women with VMS associated with menopause. CLINICAL TRIAL REGISTRATION: None.

Epidemiology and treatment patterns of UK women diagnosed with vasomotor symptoms: Findings from the Clinical Practice Research Datalink GOLD database.

OBJECTIVES: To describe the epidemiology and treatment of vasomotor symptoms (VMS) in the UK. STUDY DESIGN: Retrospective study that used electronic medical records from UK primary care centers. MAIN OUTCOME MEASURES: The prevalence and incidence of moderate-to-severe VMS, the proportion treated, persistence with initial treatment, treatment patterns, and menopausal hormone therapy (HT) experience were investigated over the study period (Jan. 2009-Dec. 2018). The study population comprised women aged 40-65 years registered at general practitioner clinics. For incident cases, the uptake of pharmacological non-hormonal or hormonal treatment was recorded, which included experience of HT. RESULTS: Over the 10-year study period, 1,481,646 women were included from the database, among whom there were 313,031 prevalent and 90,434 incident cases of VMS. Annual prevalence and incidence rates were stable over time, with a weighted average of 21.1 % and 15.3 per 1000 person-years, respectively (results varied across age groups). Among women who were incident VMS cases, 32.4 % (29,275) were initially prescribed non-hormonal treatments for a median of 3.9 months, 49.4 % (44,700) were prescribed hormonal treatments for 4.0 months, and 18.2 % (16,459) had no treatment. Approximately one-third of treated women switched between non-hormonal and hormonal treatments. The HT experience results showed that 52.7 % (47,639) of women were HT-eligible, 13.1 % (11,872) were HT-contraindicated (they may or may not have received HT), and 34.2 % (30,923) did not receive HT. CONCLUSIONS: Variations in prescribed treatment patterns suggest that education may be needed for clinicians and women regarding the potential pharmacological options for treating VMS in the UK.

Use of Steroids in COVID-19 Patients: What is known?

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.

Anticholinergic Burden and Associated Healthcare Resource Utilization in Older Adults with Overactive Bladder.

BACKGROUND: Bladder anticholinergics are the most widely used drugs to treat overactive bladder (OAB) but can contribute to cumulative anticholinergic burden, which may be associated with adverse outcomes. OBJECTIVE: This study aimed to evaluate the association between cumulative anticholinergic burden and healthcare resource utilization (HRU) and costs in older adults with OAB. MATERIALS AND METHODS: This was a retrospective, observational study that used data from the UK Clinical Practice Research Datalink (CPRD) GOLD database. Participants were aged ≥ 65 years with ≥ 3 years of continuous enrolment before and ≥ 2 years after the index date (date of OAB diagnosis or first prescription for any OAB drug between 1 April 2007 and 31 December 2015). The primary endpoint was the association between cumulative anticholinergic burden (assessed using the Anticholinergic Cognitive Burden [ACB] scale during the 3-year pre-index period) and HRU (GP consultations, specialist referrals, urological tests, hospital admissions) over the 2-year post-index period. RESULTS: Data from 23,561 adults were included in the analysis. Mean (SD) ACB scores in the pre- and post-index periods were 1.0 (1.1) and 2.4 (1.7), respectively; urological drugs contributed most (58.8%) to the latter. For the primary endpoint, higher pre-index ACB scores were associated with higher post-index HRU and costs. Mean (SD) ACB scores in the post-index period were 1.2 (1.3) and 2.5 (1.7) in those treated with mirabegron (beta-3 agonist) or bladder anticholinergics, respectively. LIMITATIONS: The generalizability of the results outside the UK is unclear. CONCLUSIONS: In older adults with OAB, higher anticholinergic burden before initiating OAB drugs is associated with higher HRU and costs. When making treatment decisions in older adults, consideration should be given to assessing the existing anticholinergic burden and using OAB treatments that do not add to this burden.

Global cross-sectional survey of women with vasomotor symptoms associated with menopause: prevalence and quality of life burden.

OBJECTIVE: To determine prevalence and health-related quality of life (HRQOL) of moderate-to-severe vasomotor symptoms (VMS) in postmenopausal women in Europe, the US, and Japan, and among subgroups of women not taking hormone therapy (HT). METHODS: Screening surveys were sent to a random sample of women aged 40 to 65 years; full questionnaires followed to those who completed them and met inclusion criteria. Women with successfully treated VMS, breast cancer, or on HT for medical conditions were excluded. The Menopause-Specific QOL (MENQOL) and Work Productivity and Activity Impairment (WPAI) questionnaires were included in the questionnaire. RESULTS: Of 25,161 women completing the screening survey, 11,771 were postmenopausal and 3,460 met inclusion criteria and completed the full questionnaire. Prevalence of moderate-to-severe VMS was 40%, 34%, and 16% in Europe, the US, and Japan, respectively. A large proportion were HT averse, albeit eligible (Europe 56%, US 54%, Japan 79%). In total, 12%, 9%, and 8% in Europe, the US, and Japan, respectively, were HT-contraindicated. A high proportion were HT-cautious (Europe 70%, US 69%, Japan 52%). Most common menopausal symptoms reported in the MENQOL were feeling tired or worn out (Europe/US 74%, Japan 75%), aching in muscles and joints (Europe 69%, US 68%, Japan 61%), difficulty sleeping (Europe 69%, US 66%, Japan 60%), and hot flashes (Europe 67%, US 68%, Japan 62%). Overall, the most bothersome symptom was weight gain. As measured by the WPAI, hot flashes and night sweats had a greater impact on daily activities than on working activities. CONCLUSIONS: A high proportion of women experienced moderate-to-severe VMS, with associated symptoms impacting QOL.

Qualitative study: burden of menopause-associated vasomotor symptoms (VMS) and validation of PROMIS Sleep Disturbance and Sleep-Related Impairment measures for assessment of VMS impact on sleep.

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.

Fezolinetant in the treatment of vasomotor symptoms associated with menopause.

Introduction: Although international clinical practice guidelines recognize a continued role for menopausal hormone therapy (HT), particularly for symptomatic women <60 years of age or within 10 years of menopause, safety and tolerability concerns have discouraged HT use due to potential links with a perceived increased risk of hormone-dependent cancers, and an established risk of stroke and venous thromboembolism. There is therefore a need for safe, effective non-hormonal therapy for relief of menopausal vasomotor symptoms (VMS).Areas covered: This narrative review summarizes the dataset accrued for fezolinetant, a neurokinin-3 receptor (NK3R) antagonist in clinical development for menopause-associated VMS.Expert opinion: Altered signaling in neuroendocrine circuits at menopause leads to VMS wherein NK3R activity plays a key role to modulate the thermoregulatory center in a manner conducive to triggering the 'hot flash' response. Thus, a new generation of NK3R antagonists has entered clinical development to specifically target the mechanistic basis of VMS. Fezolinetant is the most advanced NK3R antagonist in terms of stage of clinical development. Results to date have demonstrated rapid and substantial reduction in VMS frequency and severity and associated improvements in health-related quality of life. NK3R antagonists offer a non-hormonal alternative to HT for the treatment of menopause-related VMS.

Validation of the Overactive Bladder-Bladder Assessment Tool (OAB-BAT): A Potential Alternative to the Standard Bladder Diary for Monitoring OAB Outcomes.

BACKGROUND: An advisory board concluded that a new, comprehensive overactive bladder (OAB) patient-reported outcome (PRO) measure should be developed in accordance with regulatory guidelines. The OAB-Bladder Assessment Tool (OAB-BAT) was developed with qualitative input from OAB patients and experts to measure symptoms, bother, impacts, and satisfaction with treatment. OBJECTIVE: Psychometric evaluation of the OAB-BAT assessing PRO OAB symptoms, bother, and impacts during a 7-d recall period. DESIGN, SETTING, AND PARTICIPANTS: Psychometric testing was conducted for a 28-d observational study of 170 OAB patients. Eligibility criteria included clinician-confirmed OAB diagnosis with at least eight micturitions per day. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Assessments included the OAB-BAT, a 7-d bladder diary, and co-validating OAB PROs. Analysis included classical and modern test theories. A scoring algorithm was developed and psychometric properties were assessed. RESULTS AND LIMITATIONS: The majority of participants were women (72.4%) with moderate OAB symptom severity (53.5%). More than one-third of participants (34.1%) were incontinent. Responses were well balanced across bother and impact items, while symptom frequency items showed sparse responses. Analysis supported an eight-item unidimensional model based on bother and impacts. No items performed differently by gender or continence status. The OAB-BAT showed internal consistency (ω=0.918), retest reliability (two-way random intraclass correlation coefficient=0.81), and convergent validity with the OAB-q (r>0.4). Known groups showed the expected trend. Comparisons between OAB-BAT scores and components of the bladder diary showed a moderate effect size (r>0.4). CONCLUSIONS: The eight-item OAB-BAT with 7-d recall is valid and reliable as an OAB PRO measure. Structural modeling, balanced with content validity considerations, produced robust scores. The OAB-BAT is a useful addition to the clinical assessment of patients, designed to complement the use of bladder diaries for monitoring OAB outcomes, in clinical trial and clinical practice environments. Future studies will need to assess the treatment satisfaction items in a larger sample of patients receiving OAB treatment. PATIENT SUMMARY: We tested a questionnaire designed to assess overactive bladder (OAB) symptoms, bother, satisfaction, and impacts by asking patients to complete it on a weekly basis. We found that the questionnaire accurately captures the symptoms and impacts that are most important to patients with OAB. We conclude that the questionnaire could be a useful instrument and, after further assessment in clinical practice and research, a possible alternative to a bladder diary in measuring OAB outcomes.

Safety and Efficacy of Mirabegron: Analysis of a Large Integrated Clinical Trial Database of Patients with Overactive Bladder Receiving Mirabegron, Antimuscarinics, or Placebo.

BACKGROUND: Mirabegron, a ß3-adrenoreceptor agonist, is an alternative drug to antimuscarinics for overactive bladder (OAB) symptoms. OBJECTIVE: To summarise safety and efficacy reporting of mirabegron treatment for OAB symptoms. DESIGN, SETTING, AND PARTICIPANTS: Pooled data analysed from 10 phase 2-4, double-blind, 12-wk mirabegron monotherapy studies in adults with OAB who had received one or more doses of study drug. INTERVENTION: Mirabegron: 25 and 50mg; antimuscarinics: solifenacin (2.5, 5, and 10mg) and tolterodine extended release (4mg). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Baseline OAB-related characteristics, intrinsic and extrinsic factors, and analyses by age (<65 vs ≥65yr and <75 vs ≥75yr) and sex were assessed. Solifenacin 2.5 and 10mg groups were not included in the efficacy analyses (small patient numbers). Safety was evaluated using the proportion of treatment-emergent adverse events. Efficacy variables were derived from bladder diaries (baseline and week 12). RESULTS AND LIMITATIONS: Baseline hypertension and diabetes were more frequent across treatment groups in the older versus younger age groups and in men versus women. Within sexes, frequencies were similar between treatment groups. Some differences were observed in baseline characteristics, including type of incontinence and medical history between sexes. No previously unreported safety concerns were identified. Improvements in efficacy (mean number of incontinence episodes/24h, micturitions/24h, urgency episodes/24h, volume voided/micturition, and nocturia episodes) versus placebo were observed in all treatment groups. Significant treatment-by-subgroup interactions included change from baseline in the mean number of incontinence episodes/24h by age (<65 vs ≥65yr), nocturia by age (<65 vs ≥65yr and <75 vs ≥75yr), and urgency episodes by previous OAB medication. CONCLUSIONS: Data from this integrated database of 10 mirabegron studies reaffirm the safety and efficacy profiles of mirabegron, solifenacin, and tolterodine in adults of different age groups and sexes. PATIENT SUMMARY: Overactive bladder is a complex of symptoms including a compelling desire to pass urine that leads to increased frequency, which may lead to a degree of incontinence if you do not reach the toilet in time and may wake you from sleep. We pooled data from 10 different studies of mirabegron in patients with overactive bladder symptoms, and looked at the effect in the total number of patients who received the treatment, as well as in different age groups and between men and women. No new safety concerns were identified, and mirabegron improved the symptoms of overactive bladder.

Clinical outcome of paediatric patients with traumatic brain injury (TBI) receiving 3% hypertonic saline (HTS) in the emergency room of a tertiary care hospital.

OBJECTIVE: 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). METHODOLOGY: 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. RESULTS: 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. CONCLUSIONS: Paediatric patients with TBI receiving 3% hypertonic saline results in improved GCS and a decrease in the length of hospital stay.