Burden of adult atopic dermatitis and unmet needs with existing therapies.

OBJECTIVE: Patients with atopic dermatitis (AD) have low treatment satisfaction. In this study, we evaluated the humanistic burden, treatment satisfaction, and treatment expectations in patients with AD in the United States. METHODS: Adults with AD recruited through the National Eczema Association and clinical sites completed a web-based survey comprising the Patient-Oriented SCORing Atopic Dermatitis (PO-SCORAD), Dermatology Life Quality Index; Work Productivity and Activity Impairment Questionnaire-Atopic Dermatitis; Treatment Satisfaction Questionnaire for Medication (TSQM); and answered questions on healthcare provider (HCP) visits, treatment history, and treatment goals. Descriptive analyses were performed to compare participants by severity. RESULTS: Among 186 participants (mean [standard deviation] age 39.7 [15.3] years, 79.6% female), 26.9%, 44.6%, and 26.3% of the participants had mild, moderate, or severe AD, respectively, based on PO-SCORAD. Greater disease severity was associated with a greater impact on work and daily life, decreased TSQM scores, and increased HCP visits. Corticosteroid topical cream or ointment (53.8%) and oral antihistamines (31.2%) were most commonly used for the treatment of AD. Participants reported declining/stopping/changing AD treatment due to the potential for side effects or lack of efficacy. 'Leading normal lives' (28.0%) and 'being itch-free' (33.9%) were important treatment goals. CONCLUSIONS: Individuals with AD, especially severe disease, face a considerable humanistic burden even while using treatment.

Dysphagia Days as an Assessment of Clinical Treatment Outcome in Eosinophilic Esophagitis.

INTRODUCTION: The aim of this study was to evaluate Dysphagia Days as a measure of symptom improvement in patients with eosinophilic esophagitis from the HEROES study. METHODS: Dysphagia Days, defined as a yes answer to the following question: During any meal today, did food go down slowly or get stuck in your throat or chest? was assessed for cendakimab vs placebo. RESULTS: A statistically significant reduction in the mean number of Dysphagia Days experienced was observed with cendakimab 360 mg vs placebo at week 16 (-4.67 vs -1.83; P = 0.0115); an even greater improvement was observed in steroid-refractory patients vs placebo (-4.48 vs -0.04; P = 0.0079). DISCUSSION: Dysphagia Days represents a relevant clinical end point to capture dysphagia-related symptoms.

Nocturnal polyuria in women: results from the EpiNP study.

INTRODUCTION AND HYPOTHESIS: Data from a large US population-based, cross-sectional, epidemiological study (the EpiNP Study) were used to assess the symptoms and bother experienced by women with nocturnal polyuria (NP). METHODS: Consenting participants recruited from an online panel completed the baseline EpiNP survey online (Lower Urinary Tract Symptoms Tool and urological comorbidities). All reporting ≥2 voids/night and a random sample of 100 respondents, each reporting 0 or 1 void/night were asked to complete a 3-day web-based bladder diary recording time, volume, and urgency rating of each void. NP was calculated by the proportion of urine production that occurred during nocturnal hours using a Nocturnal Polyuria Index (NPI33) threshold of >0.33 or nocturnal urine production of >90 ml/h (NUP90). The frequency of participants reporting LUTS and bother was determined by age and NP: idiopathic NP, NP associated with overactive bladder (NPOAB), NP associated with comorbidities (NPCom), and no NP (did not meet NP criteria). RESULTS: A total of 5,290 women completed the baseline survey. Mean age (range) was 54.9 (30-95) years; 1,841 (34.8%) reported ≥2 nocturnal voids. The prevalence of LUTS increased across the lifespan; however, bother associated with each LUTS decreased with increasing age. The percentage of women rating bother by nocturia episodes ≥2 "> somewhat" ranged from 40.3% to 68.3%, with bother ratings highest in the NPOAB and No NP groups. CONCLUSIONS: NP is prevalent in women with considerable bother and is often associated with other urinary symptoms. Multifactorial causes and potential treatments of NP should be considered, particularly at a later age.

The patient burden of nocturnal polyuria in the United States: Results from the epidemiology of nocturnal polyuria (EpiNP) study.

OBJECTIVES: To explore the impact of nocturnal polyuria (NP) on health-related quality of life (HRQoL), work productivity, mental health, fatigue, bother, and daytime sleepiness. MATERIALS AND METHODS: This large-scale, US population-representative epidemiologic study was conducted in two parts: a web-based survey and 3-day bladder diary. Consenting participants completed the baseline Epidemiology of NP (EpiNP) survey online (Lower Urinary Tract Symptoms [LUTS] Tool, comorbidities, burden, and multiple HRQoL measures). Participants who reported ≥2 voids/night, and a random sample of 100 respondents each reporting 0 or 1 void/night, were sent urine measurement containers and asked to complete the 3-day bladder diary. NP was defined as Nocturnal Polyuria Index >0.33 (NPI33) or nocturnal urine production >90 ml/h (NUP90). Five subgroups were created: Idiopathic NP (NP with no underlying cause), NP associated with symptoms of overactive bladder (NPOAB) or bladder outlet obstruction (NPBOO; men only), NP associated with other comorbidities (NPCOM; e.g., diabetes, hypertension, heart disease, sleep apnea), and no NP (did not meet NP criteria). RESULTS: A total of 4893 men and 5297 women completed the EpiNP survey; mean age was 54.4 (SD = 14.7). Significantly greater patient burden (p < 0.0001) was evidenced in the nocturia group (≥2 voids/night) versus no nocturia group (0-1 void/night) on daily impact of nocturia, LUTS Bother, prostate symptoms (men only), work productivity, physical and mental health component scores, depression, fatigue, and daytime sleepiness. NP subgroup analyses showed men in the NPBOO group and women in the NPOAB group reported the greatest impact on LUTS bother, fatigue, physical health, work productivity impairment, daytime sleepiness, and depression (women only). CONCLUSION: This was the first large-scale, epidemiologic study to explore the impact of different forms of NP on patients' HRQoL. Findings demonstrate that NP associated with other urologic or comorbid conditions appears to have greater patient burden than idiopathic NP, in particular for women.

Validation and Meaningful Change Thresholds for an Objective Cough Frequency Measurement in Chronic Cough.

PURPOSE: Objective cough frequency is used to assess efficacy of chronic cough (CC) treatments. The objective of this study was to explore the relationship between objective cough frequency and cough-specific patient-reported outcomes (PROs) and estimate a clinically meaningful change threshold (MCT) for objective cough frequency. METHODS: Data collected in a phase 2b study in participants with refractory or unexplained CC were used to investigate the relationship between 24-h cough frequency (measured using an ambulatory cough monitor) and cough-specific PROs (i.e., cough severity visual analog scale, cough severity diary, Leicester Cough Questionnaire). Convergent validity was assessed using Spearman ρ. An MCT for 24-h cough frequency was estimated using the patient global impression of change (PGIC) scale as an anchor. RESULTS: Correlations between 24-h cough frequency and cough-specific PROs at baseline, Week 4, and Week 12 were significant (P < 0.0001) but low to moderate in strength (ρ = 0.30-0.58). Participants categorized as very much improved/much improved (i.e., PGIC of 1 or 2) or minimally improved (i.e., PGIC of 3) had mean 24-h cough frequency reductions of 55% and 30%, respectively. Receiver operating characteristic curve analysis suggested that a 24-h cough frequency reduction of 38% optimizes sensitivity and specificity for predicting a PGIC score of 1-3. CONCLUSION: Objective 24-h cough frequency is significantly associated with cough-specific PROs, but cough frequency and PROs most likely capture distinct aspects of CC. A ≥ 30% reduction in 24-h cough frequency is a reasonable MCT to define treatment response in CC clinical trials.

Understanding the patient experience of living with notalgia paresthetica: A qualitative interview study.

Background: Notalgia paresthetica (NP) is a chronic sensory neuropathy that causes intense pruritus, typically affecting the upper portion of the back and lasting for months to years. The impacts of pruritus and the full symptom experience are not well documented. Objective: To describe patients' NP symptom experience and the impacts of living with NP-related itch. Methods: Semistructured, one-to-one qualitative telephone interviews were conducted in adults living with NP. The worst itch severity during the previous 24 hours was assessed using an 11-point numerical rating scale. Results: Thirty participants (23 females; aged 41-80 years) completed interviews. Seventeen NP-related symptoms were described, with daily itch being the most common. Participants' itch ranged from severe to very severe (50%) and was experienced for a median of 2.8 years. Most (73%) participants were not receiving treatment for NP at the time of the study. Other reported symptoms included skin pain or sensitivity and secondary symptoms from itching (skin discoloration, lumps or bumps, bleeding or scabbing). NP-related itch was frequently reported to affect mood, interfere with sleep, and disrupt self-care. Limitations: Only English-speaking participants living in the United States were included. Conclusion: This study highlights the patient experience of living with NP and findings reveal that there remains an unmet need for effective therapeutic options to address NP-related itch.

Leicester Cough Questionnaire validation and clinically important thresholds for change in refractory or unexplained chronic cough.

INTRODUCTION: The Leicester Cough Questionnaire (LCQ), a cough-specific quality-of-life measure, evaluates the impact of cough across physical, psychological, and social domains in patients with chronic cough (CC). This study assessed the psychometric properties of the LCQ. METHODS: Data from a phase IIb, randomized controlled trial of the P2X3-receptor antagonist gefapixant were analyzed (NCT02612610). Subjective [Cough Severity Diary, cough severity visual analogue scale, and patient global impression of change (PGIC)] and objective (awake and 24-h cough frequency) data were used to validate the LCQ for use in patients with refractory or unexplained CC (RCC and UCC, respectively). Psychometric analyses included confirmatory factor analyses, internal consistency and test-retest reliability, validity, responsiveness, and estimated within-patient thresholds for clinically meaningful change. RESULTS: Model-fit values for the proposed three-factor LCQ domains and most individual items were acceptable. Analyses suggest that a mean improvement ranging from 1.3 to 2.3 points for the LCQ total and ⩾0.8, ⩾0.9, and ⩾0.8 points for physical, psychological, and social domain scores, respectively, had the best sensitivity and/or specificity for predicting patient ratings of improvement on the PGIC. CONCLUSIONS: The LCQ is a valid and reliable measure to evaluate cough-specific quality of life and is a fit-for-purpose measure for use in patients with RCC or UCC. Although a single threshold for defining clinically meaningful change depends on the context of use, the results can help guide both treatment decisions and drug development. Therefore, clinicians may consider a ⩾1.3-point increase in the LCQ total score as clinically meaningful.

Differences in the Prevalence of Nocturnal Polyuria in the U.S. by Definition: Results from the Epidemiology of Nocturnal Polyuria Study.

PURPOSE: Prevalence data on nocturnal polyuria (NP), nocturia caused by overproduction of urine during sleep, is primarily limited to men and varies by NP definition. This U.S.-representative epidemiological study of men and women ≥30 years old assessed the prevalence of NP. MATERIALS AND METHODS: Consenting participants completed the baseline EpiNP (Epidemiology of Nocturnal Polyuria) survey (eg Lower Urinary Tract Symptoms Tool, comorbidities). All reporting ≥2 voids/night and a target of 100 random respondents reporting 0 or 1 void/night were asked to complete 3-day bladder diaries. NP was defined as nocturnal polyuria index (NPI) >0.33 (NPI33) and nocturnal urine production >90 ml/hour (NUP90). Extrapolated prevalence was stratified by sex and subgroups: idiopathic (without underlying causes), associated with overactive bladder (NPOAB), bladder outlet obstruction (NPBOO; men) and comorbidities. Voided volumes and timing, including first uninterrupted sleep period, were assessed by subgroup. RESULTS: A total of 10,190 individuals completed the baseline survey; mean age (range) was 54.4 (30-95). A total of 3,938 individuals were invited to complete the diary; 1,763 (49.3%) completed 3-day bladder diaries. Urine production (maximum nighttime volume, total volume, nocturnal urine production, nocturia index) was higher in both men and women with idiopathic NP and comorbidities. The median number of nighttime voids was greatest for NPBOO in men and NPOAB in women. Bother associated with nighttime voiding differed by NP subgroup but was highest in NPBOO for men (NPI33: 69.6%; NUP90: 71.1%) and NPOAB for women (NPI33: 67.5%; NUP90: 66.0%). CONCLUSIONS: This population-based NP prevalence study including men and women characterizes NP subgroups and provides insights into nocturia treatment by emphasizing factors influencing urine production versus factors influencing bladder capacity.

Developing a Conceptual Disease Model of Patient Experiences and Identifying Patient-Reported Clinical Outcome Assessments for Use in Trials of Treatments for Focal Onset Seizures.

Purpose: To identify concepts important to understanding the experiences of adults with focal onset seizures (FOS) and evaluate clinical outcome assessments (COAs) for measuring these concepts in clinical trials of treatments for FOS. Methods: A search of published qualitative research, clinical trials, and approved product labels for FOS treatments was performed to develop a conceptual disease model (CDM) of patients' experience of living with FOS. Concepts of interest (COI) were selected, and a second literature search was conducted to identify COAs measuring these concepts. Ten COAs were selected and reviewed to document their development process, evidence of measurement properties, and methods for interpreting change scores using criteria proposed in regulatory guidelines for patient-reported outcomes to support label claims. Results: Concepts identified from the published literature (13 articles, 1 conference abstract), 24 clinical trials, and 8 product labels were included in a novel CDM. Impacts on physical, cognitive, and social and emotional function were chosen as COI for evaluating treatment outcomes for FOS; the additional concept of social support and coping strategies was chosen to understand patients' lived experiences. From 51 unique COAs identified, 10 were selected based on their potential coverage of the COI; some symptom severity and health-related quality of life (HRQoL) COAs covered multiple COI. Of these 10, 8 COAs evaluated impacts/limitations on physical function, 8 measured social and emotional impacts, and 5 assessed social support and coping strategies. While most assessments had gaps in evidence validating their measurement properties, 2 COAs measuring symptom severity and 1 COA measuring HRQoL had evidence confirming their potential utility in clinical trials to support label claims. Conclusion: This research provides insights into the experience of patients with FOS and identifies COAs that measure concepts considered to support endpoints in clinical trials for FOS.

Time to response for clinical and patient-reported outcomes in patients with psoriatic arthritis treated with tofacitinib, adalimumab, or placebo.

BACKGROUND: This study examined the time to clinically meaningful response in patients with active psoriatic arthritis treated with tofacitinib, adalimumab, or placebo switching to tofacitinib. METHODS: Data were from two phase 3 studies, OPAL Broaden (12 months) and OPAL Beyond (6 months). Patients received tofacitinib 5 or 10 mg twice daily (BID), adalimumab 40 mg once every 2 weeks (OPAL Broaden only), or placebo switching to tofacitinib 5 or 10 mg BID at month 3. Baseline to initial response time was according to pre-defined clinically meaningful criteria on Health Assessment Questionnaire-Disability Index (HAQ-DI; ≥ 0.35-point improvement), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F; ≥ 4-point improvement), Psoriatic Arthritis Disease Activity Score (PASDAS; post-baseline score ≤ 3.2 and > 1.6-point improvement from baseline), and minimal disease activity (MDA; meeting at least 5 of 7 criteria) composite. RESULTS: In OPAL Broaden, median time to initial HAQ-DI score response was 29, 53, and 30 days in patients treated with tofacitinib 5 mg BID, tofacitinib 10 mg BID, or adalimumab, compared with 162 and 112 days in patients treated with placebo switching to tofacitinib 5 or 10 mg BID at month 3, respectively. Across studies, median time to initial FACIT-F total score response was shorter in patients receiving tofacitinib 5 mg BID (31 days) vs other groups (84-92 days). Median time to initial response was approximately 11 (MDA)/6-9 months (PASDAS) in tofacitinib/adalimumab groups in OPAL Broaden. CONCLUSION: This analysis demonstrates tofacitinib's efficacy on most patient-reported and clinical endpoints over time and shows a shorter time to initial, clinically meaningful response in patients receiving tofacitinib vs patients switching from placebo to tofacitinib. TRIAL REGISTRATION: ClinicalTrials.gov , NCT01877668. Registered June 12, 2013. ClinicalTrials.gov , NCT01882439. Registered June 18, 2013.

The Prevalence of Nocturnal Polyuria in the United States: Results from the Epidemiology of Nocturnal Polyuria Study.

BACKGROUND: The prevalence of nocturnal polyuria (NP), which is passing large volumes of urine during the main sleep period, has been investigated primarily in middle-aged to older men. There is thus a gap in the NP evidence base for women and for younger individuals. OBJECTIVE: To estimate the prevalence of nocturia due to NP in the USA. DESIGN, SETTING, AND PARTICIPANTS: This large epidemiologic study used a US population-representative sample of men and women aged ≥30 yr to assess the prevalence of NP (NCT04125186). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Consenting participants completed an online survey (Lower Urinary Tract Symptoms Tool and comorbidities). All who reported two or more voids per night and 100 random respondents each reporting no or one void per night were asked to complete a 3-d bladder diary. Two NP definitions were used: nocturnal urine production >90 ml/h (NUP90) and Nocturnal Polyuria Index >0.33 (NPI33). Crude and population-adjusted prevalence results were calculated from completed diaries for the following subgroups by sex and age: idiopathic NP; NP with overactive bladder (NP-OAB) or bladder outlet obstruction (NP-BOO; men only); NP associated with other comorbidities; and no NP (did not meet the NPI33 or NUP90 definition). RESULTS AND LIMITATIONS: Among the 10,190 respondents who completed the survey, the mean age was 54.4 yr (range 30-95); 3,339 reported two or more nocturnal voids and 1,763 completed the 3-d diary (response rate 49.3%). The adjusted overall NP prevalence was 31.5% among men and 38.5% among women using the NPI33 definition, and 23.8% among men and 18.1% among women using NUP90. The adjusted idiopathic NP prevalence was lower among men (NPI33: 5.2%; NUP90: 1.4%) than among women (NPI33: 9.8%; NUP90: 4.0%). The prevalence of idiopathic NP decreased with age as NP associated with other possible causes increased with age in men (most common, BOO) and women (most common, OAB). CONCLUSIONS: This is the first population-based study of NP prevalence to include men, women, and young adults. NP is common; a multifactorial etiology should be considered, particularly as age increases. PATIENT SUMMARY: In this population-based US study, we examined the frequency of nighttime urination among men and women aged ≥30 y and older. We found that nighttime urination is common among men and women. Many conditions can lead to increased nighttime urination as people age.

Patient-Reported Disease Burden and Unmet Therapeutic Needs in Atopic Dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a common, chronic, relapsing, inflammatory skin disease causing a variety of dermatologic signs and symptoms, affecting patient’s quality of life. While treatment options are available, they are of variable effectiveness. This study sought to characterize patient-reported AD signs and symptoms, flare, and associated bother, by disease severity and control. METHODS: Adults diagnosed with AD were recruited through the National Eczema Association (NEA) and clinical sites and completed a web-based survey including the Patient-Oriented SCORing Atopic Dermatitis (PO-SCORAD), Recap of Atopic Eczema (RECAP), and Skin Pain numeric rating scale (NRS), as well as questions on previous/current clinical presentation, flare frequency and severity, past/ present AD treatment, and sociodemographic characteristics. RESULTS: A total of 186 participants completed the survey (mean age 39.7 years, 80% female). The most frequently reported current AD signs and symptoms included dryness, itch, redness, roughness, and flaking skin, and the most bothersome were itch, dryness, and redness (63%). The majority of participants (84%) were either currently experiencing a flare or had experienced one within the past month. The most common signs and symptoms that grew worse during the most recent flare were itch and redness across all disease severity groups. Participants most often experienced one to three flares in the last three months. Flare frequency, duration, and average severity increased with greater disease severity and lack of disease control. CONCLUSIONS: The results of this study demonstrate the diverse and considerable symptomatic burden experienced by people with AD, even while being treated for AD. J Drugs Dermatol. 2021;20(11):1222-1230. doi:10.36849/JDD.6329.

Measuring respiratory symptoms in moderate/severe asthma: evaluation of a respiratory symptom tool, the E-RS®: COPD in asthma populations.

BACKGROUND: Symptom constructs included in the Evaluating Respiratory Symptoms in Chronic Obstructive Pulmonary Disease (E-RS®: COPD) tool may be relevant to patients with asthma. The purpose of this study was to evaluate content validity and psychometric performance of the E-RS: COPD in moderate/severe asthma patients. METHODS: Content validity of the E-RS: COPD was evaluated in patients with moderate/severe asthma using concept elicitation and cognitive debriefing interviews. Secondary analyses using data from two clinical trials in patients with moderate/severe asthma evaluated the factor structure of the E-RS: COPD plus two supplementary items (wheeze; shortness of breath with strenuous physical activity) and assessed psychometric properties of the tool, which will be referred to as E-RS®: Asthma when used in asthma populations. RESULTS: Qualitative interviews (N = 25) achieved concept saturation for asthma respiratory symptoms. Concepts in the E-RS: COPD were relevant to patients and instructions were understood. Most patients (19/25; 76%) reported experiencing all concepts in the E-RS: COPD; no patients indicated missing symptoms. Secondary analyses of clinical trial data supported the original factor structure (RS-Total and three symptom-specific subscales). The two supplemental items did not fit with this factor structure and were not retained. RS-Total and subscale score reliability was high (internal consistency [α] > 0.70). Validity was demonstrated through significant (P < 0.0001) relationships with the St George's Respiratory Questionnaire (SGRQ) and Asthma Symptom Severity scale. E-RS: Asthma was responsive to change when evaluated using SGRQ, Patient Global Impression of Change and Asthma Quality of Life Questionnaire as anchors (P < 0.0001). Clinically meaningful change thresholds were also identified (RS-Total: - 2.0 units). CONCLUSIONS: The E-RS: Asthma is reliable and responsive for evaluating respiratory symptoms in patients with moderate/severe asthma.

Validation of a visual analog scale for assessing cough severity in patients with chronic cough.

INTRODUCTION: Patients with chronic cough experience considerable burden. The cough severity visual analog scale (VAS) records patients' assessment of cough severity on a 100-mm linear scale ranging from "no cough" (0 mm) to "worst cough" (100 mm). Although cough severity scales are widely used in clinical practice and research, their use in patients with refractory or unexplained chronic cough has not been formally validated. METHODS: This analysis includes data from a phase 2b randomized controlled trial of the P2X3-receptor antagonist gefapixant for treatment of refractory or unexplained chronic cough (NCT02612610). Cough severity VAS scores were assessed at baseline and Weeks 4, 8, and 12. The cough severity VAS was validated using several outcomes, including the Cough Severity Diary (CSD), Leicester Cough Questionnaire (LCQ), patient global impression of change (PGIC) scale, and objective cough frequency. Validation metrics included test-retest reliability, convergent and known-groups validity, responsiveness, and score interpretation (i.e., clinically meaningful change threshold). RESULTS: The analysis included 253 patients (median age, 61.0 years; females, 76%). Test-retest reliability of the cough severity VAS was moderate (intraclass correlation coefficient, 0.51). The cough severity VAS had acceptable convergent validity with other related measures (Pearson r of 0.53 and -0.41 for CSD and LCQ total scores, respectively; p < 0.0001 for each). Known-groups validity was supported by significant differences in mean cough severity VAS scores across severity groups defined using CSD, LCQ, and cough frequency tertiles. A large effect size was observed in patients with the greatest improvements in PGIC (Cohen d = -1.8). A ⩾ 30-mm reduction in the cough severity VAS was estimated as a clinically meaningful change threshold for clinical trials in chronic cough. CONCLUSIONS: The cough severity VAS is a valid and responsive measure. A cough severity VAS reduction of ⩾ 30 mm can discriminate clinically meaningful changes in chronic cough severity in clinical studies.

Quantitative measurement properties and score interpretation of the Cough Severity Diary in patients with chronic cough.

AIMS: The Cough Severity Diary (CSD) was developed in accordance with the FDA guidance for patient-reported outcome measures and is focused on capturing the patient's perception of cough in terms of frequency, intensity, and disruption due to their cough. The measure includes a series of seven items asking patients to rate the frequency (three items), intensity (two items), and disruptiveness (two items) of their cough. The instrument was designed to be completed daily before bedtime, has a recall period of 'today,' and responses to items are entered on an 11-point numeric rating scale ranging from 0 to 10 with anchors on each end. The objective of this analysis was to confirm the domain structure of the CSD and assess its reliability, validity, and responsiveness in adult patients with refractory or unexplained chronic cough (RCC/UCC). Criteria for defining meaningful changes in mean weekly CSD total and domain scores in the context of a clinical trial were also developed. METHODS: Pooled data from a phase II randomized controlled trial of an investigational treatment for RCC/UCC were analyzed. Participants were non-smokers, had RCC/UCC for ⩾1 year, and a baseline cough severity visual analogue scale (VAS) ⩾40 mm. CSD scores (baseline, week 4), were analyzed; the Leicester Cough Questionnaire (LCQ), cough severity VAS, Patient Global Impression of Change (PGIC), and objective cough frequency counts were used for validation. CSD domain structure (Total, Frequency, Intensity, Disruption) was assessed for scoring. RESULTS: A total of 253 participants were included (mean age 60.2; 76% female). Global fit of the three-factor CSD was acceptable. For the CSD total score, internal consistency (α = 0.89) and test-retest reliability (intraclass correlation coefficient = 0.68) were high. CSD total scores were correlated with the LCQ total (r = -0.62) and cough severity VAS (r = 0.84). Participants with a PGIC score of 1 or 2 (most improved groups) had the greatest mean score improvement on the CSD Total (Day 0 to Day 28), supporting responsiveness (similar findings for subscales). A change threshold of ⩾1.3-point reduction on the total and subscale scores is appropriate to define clinically meaningful improvement. CONCLUSION: The CSD is a reliable, valid, and responsive measure of cough symptom severity in patients with refractory or unexplained chronic cough and fit-for-purpose for assessing changes in cough severity in clinical trials. The reviews of this paper are available via the supplemental material section.

Understanding side effects of therapy for myasthenia gravis and their impact on daily life.

BACKGROUND: Myasthenia gravis is a chronic, autoimmune, neuromuscular junction disorder characterized by skeletal muscle weakness. Current therapies for myasthenia gravis are associated with significant side effects. The objective of this study was to characterize the side effects, and associated health-related quality of life and treatment impacts, of traditional myasthenia gravis treatments. METHODS: This study had two phases; a Phase 1 interview and a 2-part web-based survey in Phase 2 that included brainstorming (Step 1) and rating (Step 2) exercises using group concept mapping. In Phase 1, all 14 participants reported experiencing side effects from myasthenia gravis treatments which had significant impacts on daily life. In Phase 2, 246 participants contributed to Step 1; 158 returned for Step 2. RESULTS: The brainstorming exercise produced 874 statements about side effects and their impact, which were reduced to 35 side effects and 23 impact-on-daily life statements. When rating these statements on severity, frequency, and tolerability, blood clots, infections/decreased immunity, weight gain, and diarrhea were the least tolerable and most severely rated. The most frequent and severe impacts were sleep interference and reduced physical and social activities. CONCLUSIONS: Based on these findings, there appears to be a need for better and more tolerable treatments for myasthenia gravis patients.

Patient Preferences for GLP-1 Receptor Agonist Treatment of Type 2 Diabetes Mellitus in Japan: A Discrete Choice Experiment.

INTRODUCTION: The incidence and prevalence of type 2 diabetes mellitus (T2D) are increasing in Japan, and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly used to treat the disease. The objective of this study was to use a discrete choice experiment (DCE) to characterize patient preferences for clinical treatment features of two GLP-1 RAs-dulaglutide 0.75 mg and semaglutide 0.50 mg-among patients with T2D in Japan. METHODS: Adult patients with T2D in Japan were administered the DCE via a web-based survey. The DCE examined patient preferences for five treatment attributes (each described by two or three levels), including method of administration, HbA1c change, reduction in cardiovascular (CV) risk, weight change, and common side effects (i.e., nausea). Results were analyzed using multinomial and mixed logit models, and predicted choice probability was calculated to determine the overall probability that either dulaglutide or semaglutide DCE levels were preferred. One DCE choice task included a direct comparison of the dulaglutide 0.75 mg versus semaglutide 0.50 mg treatment profiles. RESULTS: 190 subjects completed the survey; 29 were excluded after failing the predefined internal validity assessments. In the final analysis sample (N = 161), the attribute with the largest effect on the subjects' choices was reduction in CV risk, followed by HbA1c change and common side effects. Patients' predicted choice probability for the semaglutide profile was 78%, versus 22% for the dulaglutide profile. 28% of patients were "very willing" to initiate treatment with semaglutide's product profile, versus 6% for dulaglutide. CONCLUSION: In this study, reduction in CV risk and HbA1c change were the key drivers of GLP-1 RA medication preference in Japanese patients with T2D. Overall, the majority of the patients preferred a product with attribute levels reflecting the semaglutide 0.50 mg profile, with a known CV risk reduction benefit and superior HbA1c reduction. FUNDING: Novo Nordisk.

Can CAPTURE be used to identify undiagnosed patients with mild-to-moderate COPD likely to benefit from treatment?

Background: COPD Assessment in Primary Care To Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE™) uses five questions and peak expiratory flow (PEF) thresholds (males ≤350 L/min; females ≤250 L/min) to identify patients with a forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) <0.70 and FEV1 <60% predicted or exacerbation risk requiring further evaluation for COPD. This study tested CAPTURE's ability to identify symptomatic patients with mild-to-moderate COPD (FEV1 60%-80% predicted) who may also benefit from diagnosis and treatment. Methods: Data from the CAPTURE development study were used to test its sensitivity (SN) and specificity (SP) differentiating mild-to-moderate COPD (n=73) from no COPD (n=87). SN and SP for differentiating all COPD cases (mild to severe; n=259) from those without COPD (n=87) were also estimated. The modified Medical Research Council (mMRC) dyspnea scale and COPD Assessment Test (CAT™) were used to evaluate symptoms and health status. Clinical Trial Registration: NCT01880177, https://ClinicalTrials.gov/ct2/show/NCT01880177?term=NCT01880177&rank=1. Results: Mean age (+SD): 61 (+10.5) years; 41% male. COPD: FEV1/FVC=0.60 (+0.1), FEV1% predicted=74% (+12.4). SN and SP for differentiating mild-to-moderate and non-COPD patients (n=160): Questionnaire: 83.6%, 67.8%; PEF (≤450 L/min; ≤350 L/min): 83.6%, 66.7%; CAPTURE (Questionnaire+PEF): 71.2%, 83.9%. COPD patients whose CAPTURE results suggested that diagnostic evaluation was warranted (n=52) were more likely to be symptomatic than patients whose results did not (n=21) (mMRC >2: 37% vs 5%, p<0.01; CAT>10: 86% vs 57%, p<0.01). CAPTURE differentiated COPD from no COPD (n=346): SN: 88.0%, SP: 83.9%. Conclusion: CAPTURE (450/350) may be useful for identifying symptomatic patients with mild-to-moderate airflow obstruction in need of diagnostic evaluation for COPD.