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.

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.

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.

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.

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.

Performance of the inFLUenza Patient-Reported Outcome (FLU-PRO) diary in patients with influenza-like illness (ILI).

BACKGROUND: The inFLUenza Patient Reported Outcome (FLU-PRO) measure is a daily diary assessing signs/symptoms of influenza across six body systems: Nose, Throat, Eyes, Chest/Respiratory, Gastrointestinal, Body/Systemic, developed and tested in adults with influenza. OBJECTIVES: This study tested the reliability, validity, and responsiveness of FLU-PRO scores in adults with influenza-like illness (ILI). METHODS: Data from the prospective, observational study used to develop and test the FLU-PRO in influenza virus positive patients were analyzed. Adults (≥18 years) presenting with influenza symptoms in outpatient settings in the US, UK, Mexico, and South America were enrolled, tested for influenza virus, and asked to complete the 37-item draft FLU-PRO daily for up to 14-days. Analyses were performed on data from patients testing negative. Reliability of the final, 32-item FLU-PRO was estimated using Cronbach's alpha (α; Day 1) and intraclass correlation coefficients (ICC; 2-day reproducibility). Convergent and known-groups validity were assessed using patient global assessments of influenza severity (PGA). Patient report of return to usual health was used to assess responsiveness (Day 1-7). RESULTS: The analytical sample included 220 ILI patients (mean age = 39.3, 64.1% female, 88.6% white). Sixty-one (28%) were hospitalized at some point in their illness. Internal consistency reliability (α) of FLU-PRO Total score was 0.90 and ranged from 0.72-0.86 for domain scores. Reproducibility (Day 1-2) was 0.64 for Total, ranging from 0.46-0.78 for domain scores. Day 1 FLU-PRO scores correlated (≥0.30) with the PGA (except Gastrointestinal) and were significantly different across PGA severity groups (Total: F = 81.7, p<0.001; subscales: F = 6.9-62.2; p<0.01). Mean score improvements Day 1-7 were significantly greater in patients reporting return to usual health compared with those who did not (p<0.05, Total and subscales, except Gastrointestinal and Eyes). CONCLUSIONS: Results suggest FLU-PRO scores are reliable, valid, and responsive in adults with influenza-like illness.

Reliability, Validity, and Responsiveness of InFLUenza Patient-Reported Outcome (FLU-PRO©) Scores in Influenza-Positive Patients.

OBJECTIVES: To assess the reliability, validity, and responsiveness of InFLUenza Patient-Reported Outcome (FLU-PRO©) scores for quantifying the presence and severity of influenza symptoms. METHODS: An observational prospective cohort study of adults (≥18 years) with influenza-like illness in the United States, the United Kingdom, Mexico, and South America was conducted. Participants completed the 37-item draft FLU-PRO daily for up to 14 days. Item-level and factor analyses were used to remove items and determine factor structure. Reliability of the final tool was estimated using Cronbach α and intraclass correlation coefficients (2-day reliability). Convergent and known-groups validity and responsiveness were assessed using global assessments of influenza severity and return to usual health. RESULTS: Of the 536 patients enrolled, 221 influenza-positive subjects comprised the analytical sample. The mean age of the patients was 40.7 years, 60.2% were women, and 59.7% were white. The final 32-item measure has six factors/domains (nose, throat, eyes, chest/respiratory, gastrointestinal, and body/systemic), with a higher order factor representing symptom severity overall (comparative fit index = 0.92; root mean square error of approximation = 0.06). Cronbach α was high (total = 0.92; domain range = 0.71-0.87); test-retest reliability (intraclass correlation coefficient, day 1-day 2) was 0.83 for total scores and 0.57 to 0.79 for domains. Day 1 FLU-PRO domain and total scores were moderately to highly correlated (≥0.30) with Patient Global Rating of Flu Severity (except nose and throat). Consistent with known-groups validity, scores differentiated severity groups on the basis of global rating (total: F = 57.2, P < 0.001; domains: F = 8.9-67.5, P < 0.001). Subjects reporting return to usual health showed significantly greater (P < 0.05) FLU-PRO score improvement by day 7 than did those who did not, suggesting score responsiveness. CONCLUSIONS: Results suggest that FLU-PRO scores are reliable, valid, and responsive to change in influenza-positive adults.

Psychometric properties of the single-item measure, severity of worst tiredness, in patients with moderately to severely active rheumatoid arthritis.

BACKGROUND: To assess the reliability, validity, and responsiveness to treatment change of the single-item measure, Severity of Worst Tiredness, in patients with rheumatoid arthritis (RA). METHODS: Data from two Phase 3, randomized, placebo-controlled (RA-BUILD; and active-controlled [RA-BEAM]), clinical studies of the efficacy of baricitinib in adults with moderately to severely active RA were used. The psychometric properties of the single-item measure, Severity of Worst Tiredness, were assessed, including test-retest reliability, convergent and discriminant validity, known-groups validity, and responsiveness, using other patient- and clinician-reported outcomes frequently assessed in RA patients. RESULTS: Test-retest reliability of the Severity of Worst Tiredness was supported through large intraclass correlation coefficients (0.89 ≤ ICC ≤ 0.91). Moderate-to-large correlations were observed between this patient-reported outcome (PRO) and other related patient- and clinician-reported assessments of RA symptoms and patient functioning, supporting construct validity of the measure (│r│ ≥ 0.41). The instrument also displayed known-groups validity through statistically significant differences between mean values of the Severity of Worst Tiredness defined using other indicators of RA severity. Finally, responsiveness was supported by large and statistically significant differences in change scores from Day 1 to Week 12 for patients comparing responders and nonresponders using the American College of Rheumatology 20 (ACR20) criteria. CONCLUSION: The Severity of Worst Tiredness PRO demonstrated adequate reliability, validity, and responsiveness in clinical trials of adults with moderately to severely active RA and is fit for purpose in this patient population.

Psychometric properties of morning joint stiffness duration and severity measures in patients with moderately to severely active rheumatoid arthritis.

BACKGROUND: To assess the measurement properties of two single-item patient-reported outcome (PRO) measures that assessed the length of time (in minutes) and severity of morning joint stiffness (MJS) experienced each day. METHODS: Data from two Phase 3, randomized placebo-controlled (and active-controlled [RA-BEAM]), clinical studies assessing the safety and efficacy of baricitinib in adults with moderately to severely active rheumatoid arthritis (RA) were used to evaluate the psychometric properties of the Duration of MJS and Severity of MJS PROs. RESULTS: Test-retest reliability of Duration of MJS and Severity of MJS was supported through large intraclass correlation coefficients among stable patients (coefficient range for both studies: 0.88 to 0.93). In support of construct validity, moderate correlations were evidenced between Duration of MJS and other related patient- and clinician-reported assessments of RA symptoms and patient functioning, whereas moderate-to-strong correlations were evidenced between these same patient- and clinician-reported assessments and Severity of MJS. Statistically significant differences between the median and mean values of Duration of MJS and Severity of MJS for differing categories of RA disease severity supported known-groups validity. Finally, large and statistically significant differences in change scores from Day 1 to Week 12 for patients defined as responders versus non-responders using the American College of Rheumatology 20 criteria supported the responsiveness of both PROs. CONCLUSION: Duration of MJS and Severity of MJS PROs demonstrated reliability, validity, and responsiveness in adults with moderately to severely active RA, supporting the measurement of these key symptoms in clinical trials.

A New Approach for Identifying Patients with Undiagnosed Chronic Obstructive Pulmonary Disease.

RATIONALE: Chronic obstructive pulmonary disease (COPD) is often unrecognized and untreated. OBJECTIVES: To develop a method for identifying undiagnosed COPD requiring treatment with currently available therapies (FEV1 <60% predicted and/or exacerbation risk). METHODS: We conducted a multisite, cross-sectional, case-control study in U.S. pulmonary and primary care clinics that recruited subjects from primary care settings. Cases were patients with COPD and at least one exacerbation in the past year or FEV1 less than 60% of predicted without exacerbation in the past year. Control subjects were persons with no COPD or with mild COPD (FEV1 ≥60% predicted, no exacerbation in the past year). In random forests analyses, we identified the smallest set of questions plus peak expiratory flow (PEF) with optimal sensitivity (SN) and specificity (SP). MEASUREMENTS AND MAIN RESULTS: PEF and spirometry were recorded in 186 cases and 160 control subjects. The mean (SD) age of the sample population was 62.7 (10.1) years; 55% were female; 86% were white; and 16% had never smoked. The mean FEV1 percent predicted for cases was 42.5% (14.2%); for control subjects, it was 82.5% (15.7%). A five-item questionnaire, CAPTURE (COPD Assessment in Primary Care to Identify Undiagnosed Respiratory Disease and Exacerbation Risk), was used to assess exposure, breathing problems, tiring easily, and acute respiratory illnesses. CAPTURE exhibited an SN of 95.7% and an SP of 44.4% for differentiating cases from all control subjects, and an SN of 95.7% and an SP of 67.8% for differentiating cases from no-COPD control subjects. The PEF (males, <350 L/min; females, <250 L/min) SN and SP were 88.0% and 77.5%, respectively, for differentiating cases from all control subjects, and they were 88.0% and 90.8%, respectively, for distinguishing cases from no-COPD control subjects. The CAPTURE plus PEF exhibited improved SN and SP for all cases versus all control subjects (89.7% and 78.1%, respectively) and for all cases versus no-COPD control subjects (89.7% and 93.1%, respectively). CONCLUSIONS: CAPTURE with PEF can identify patients with COPD who would benefit from currently available therapy and require further diagnostic evaluation. Clinical trial registered with clinicaltrials.gov (NCT01880177).

Evaluating preferences for profiles of glucagon-like peptide-1 receptor agonists among injection-naive type 2 diabetes patients in Japan.

OBJECTIVE: The objective of this study was to use a discrete choice experiment (DCE) to estimate patients' preferences for the treatment features, safety, and efficacy of two specific glucagon-like peptide-1 receptor agonists, dulaglutide and liraglutide, among patients with type 2 diabetes mellitus (T2DM) in Japan. METHODS: In Japan, patients with self-reported T2DM and naive to treatment with self-injectable medications were administered a DCE through an in-person interview. The DCE examined the following six attributes of T2DM treatment, each described by two levels: "dosing frequency", "hemoglobin A1c change", "weight change", "type of delivery system", "frequency of nausea", and "frequency of hypoglycemia". Part-worth utilities were estimated using logit models and were used to calculate the relative importance (RI) of each attribute. A chi-square test was used to determine the differences in preferences for the dulaglutide versus liraglutide profiles. RESULTS: The final evaluable sample consisted of 182 participants (mean age: 58.9 [standard deviation =10.0] years; 64.3% male; mean body mass index: 26.1 [standard deviation =5.0] kg/m(2)). The RI values for the attributes in rank order were dosing frequency (44.1%), type of delivery system (26.3%), frequency of nausea (15.1%), frequency of hypoglycemia (7.4%), weight change (6.2%), and hemoglobin A1c change (1.0%). Significantly more participants preferred the dulaglutide profile (94.5%) compared to the liraglutide profile (5.5%; P<0.0001). CONCLUSION: This study elicited the preferences of Japanese T2DM patients for attributes and levels representing the actual characteristics of two existing glucagon-like peptide-1 receptor agonists. In this comparison, dosing frequency and type of delivery system were the two most important characteristics, accounting for >70% of the RI. These findings are similar to those of a previous UK study, providing information about patients' preferences that may be informative for patient-clinician treatment discussions.