Efficacy and safety of ixekizumab in a randomized, double-blinded, placebo-controlled phase IIIb study of patients with moderate-to-severe genital psoriasis.

BACKGROUND: Genital psoriasis (GenPs) is a common, debilitating and difficult-to-treat manifestation of plaque psoriasis. However, few controlled, interventional studies of GenPs exist. OBJECTIVES: To determine the efficacy of ixekizumab vs. placebo in patients with moderate-to-severe GenPs with ≥ 1% involved body surface area (BSA). METHODS: Patients with moderate-to-severe GenPs, defined as a baseline static Physician's Global Assessment of Genitalia (sPGA-G) score of ≥ 3, with BSA ≥ 1% were randomized 1 : 1 to receive placebo (n = 74) or the recommended dosing of ixekizumab (n = 75). Major outcomes included the percentage of patients achieving 0 or 1 scores on the sPGA-G (primary end point), overall sPGA, GenPs Sexual Frequency Questionnaire (GenPs-SFQ) item 2, and ≥ 3-point improvement from baseline on the GenPs itch numerical rating scale. RESULTS: At week 12, ixekizumab was superior to placebo for sPGA-G 0/1 (73% vs. 8%, P < 0·001), overall sPGA 0/1 (73% vs. 3%, P < 0·001), GenPs-SFQ item 2 score of 0 or 1 (78% vs. 21%, P < 0·001) and genital itch (60% vs. 8%, P < 0·001). No candidiasis was reported, no deaths occurred and one (1%) serious adverse event was reported in a patient receiving placebo. CONCLUSIONS: Ixekizumab was superior to placebo for the treatment of moderate-to-severe GenPs with BSA ≥ 1%. The safety profile of ixekizumab was consistent with previous studies in moderate-to-severe plaque psoriasis.

The caregiver burden in lupus: findings from UNVEIL, a national online lupus survey in the United States.

OBJECTIVES: Lupus imposes a substantial burden on patients; however, little is known about its impact on those caring for patients with the disease. In this study, we examined the impact 'caring for patients with lupus' has on caregivers from their own perspective. METHODS: UNVEIL was a one-time online national cross-sectional survey developed in partnership with the Lupus Foundation of America and fielded targeting the US Lupus Foundation of America constituents in 2014. Eligible caregivers were adults who self-identified as unpaid caregivers of patients with lupus. Eligible caregivers had to complete a series of sociodemographic questions as well as a series of well established outcome measures, such as the Short Form 12v2 Health Survey, the Work Productivity and Activity Index, the Caregiver Burden Inventory, and the Perceived Benefits of Caregiving Scale. RESULTS: A total of 253 caregivers completed the survey. The majority of caregivers (90.1%) were aged 60 years or younger, more than half (54.2%) were men, and more than half (59.7%) identified themselves as either a spouse or a partner to the patient with lupus they were caring for. Overall health-related quality of life was close to the norm mean of the general US population. Caregivers who were employed missed an average of 12.8% of paid work time due to caregiving responsibilities and reported a 33.5% reduction in on-the-job effectiveness. Nearly half of the caregivers surveyed (49.4%) indicated that their caregiving responsibilities impacted their ability to socialize with friends, and almost all caregivers (97.6%) reported experiencing increased anxiety and stress in relation to their caregiving role. CONCLUSIONS: Caregiving for patients with lupus has a substantial impact on the work productivity and the social and emotional functioning of caregivers. Healthcare professionals and policymakers should continually assess the impact of healthcare decisions on the well-being of those caring for patients with lupus.

Psychometric properties of the Itch Numeric Rating Scale in patients with moderate-to-severe plaque psoriasis.

BACKGROUND: Itching is a profoundly distressing symptom for many patients with psoriasis, but it has not been rigorously studied using validated tools for this condition. OBJECTIVES: This study investigated the psychometric properties of the Itch Numeric Rating Scale (Itch NRS), a single-item patient-reported outcome (PRO) measuring the worst itching severity due to psoriasis in the past 24 h. METHODS: Using disease-specific clinician-rated and PRO data from one phase II and three phase III randomized clinical studies of subjects with moderate-to-severe plaque psoriasis, the Itch NRS was evaluated for test-retest reliability, construct validity and responsiveness. A responder definition was explored using anchor- and distribution-based methods. RESULTS: Test-retest reliability analyses supported the reproducibility of the measure (intraclass correlation coefficient range 0·71-0·74). To support the construct validity of the Itch NRS, large cross-sectional correlations with the Dermatology Life Quality Index (DLQI) Symptoms and Feelings domain (r ≥ 0·60 at baseline and r ≥ 0·80 at week 12) supported a priori hypotheses, while large correlations (r ≥ 0·71) between changes in Itch NRS scores and changes in DLQI Symptoms and Feelings domain scores from baseline to week 12 established responsiveness. A 4-point change was optimal for demonstrating a level of clinically meaningful improvement in itch severity after 12 weeks of treatment, which corresponds with marked clinical improvements in plaque psoriasis. CONCLUSIONS: The Itch NRS demonstrated sufficient reliability, validity and responsiveness, and appropriate interpretation standards for evaluating change over time in itch severity among patients with moderate-to-severe plaque psoriasis when validated using clinical trial data for this condition.

Psychometric validation of the Brief Pain Inventory-Short Form in patients with systemic lupus erythematosus in the United States.

This study evaluated the Brief Pain Inventory-Short Form (BPI-SF) in patients with moderate-to-severe systemic lupus erythematosus (SLE). Patients ≥18 years old who self-reported a physician diagnosis of SLE (confirmed by medical record review) and active SLE (Systemic Lupus Activity Questionnaire (SLAQ) score of ≥11) were included. The BPI-SF and Short Form Health Survey version 2 (SF-36v2) were administered electronically at baseline, week 2 and week 12. Psychometric properties of the BPI-SF were evaluated. Cronbach alphas were >0.9 for all BPI-SF items, domains and total score. Test-retest reliability correlations for responses between baseline and week 2 of the BPI-SF had intraclass correlation coefficients (ICCs) ≥0.5. The BPI-SF domains and total score were moderately positively correlated to the SLAQ score (r ≥ 0.4), but negatively correlated to the SF-36v2 bodily pain domain (r ≤ -0.6). The BPI-SF domains and total score were moderately negatively correlated to the SF-36v2 physical functioning domain and physical component summary (r ≤ -0.4), with low correlations between the BPI-SF severity domain and SF-36v2 mental component summary (r = -0.16). Assessment of pain, as measured by the BPI-SF, demonstrated validity and reliability in a sample of patients with moderate-to-severe SLE.

Osteoporosis Assessment Questionnaire-Physical Function (OPAQ-PF): a psychometrically validated osteoporosis-targeted patient reported outcome measure of daily activities of physical function.

UNLABELLED: The purpose of this study was to evaluate the measurement properties of the Osteoporosis Assessment Questionnaire-Physical Functioning (OPAQ-PF). Based on this study, the OPAQ-PF has confirmed unidimensionality and acceptable reliability, construct validity, and sensitivity to change in a recent fracture/no recent fracture osteoporosis sample. METHODS: Dimensionality was established through exploratory and confirmatory factor analysis. Patients completed three patient reported outcome (PRO) measures and four performance-based measures (PBMs) at baseline to enable an evaluation of construct validity. Patients without a recent fracture completed the OPAQ-PF 2 weeks after baseline to enable an evaluation of test-retest reliability. Ability to detect change and interpretation of change were investigated following completion of the OPAQ-PF 12 and 24 weeks postbaseline by patients with a recent fracture. RESULTS: A prospective psychometric validation study in 144 postmenopausal women, with moderate to severe osteoporosis, 37 of whom had experienced a recent fragility fracture (<6 weeks). Unidimensionality was established for the OPAQ-PF by factor analysis. The OPAQ-PF had good internal consistency (α = 0.974) and test-retest reliability (mean intraclass correlation coefficient (ICC) 0.993. The OPAQ-PF differentiated between patients with/without recent fracture, and by severity of osteoarthritis; it correlated strongly with hypothesized-related scales and PBMs (r > 0.3, p < 0.001). Ability to detect change was established with high correlations between changes in OPAQ-PF score and changes in global concept scores in recent fracture patients (r ≥ 0.6, 24-week change). Effect size of change on OPAQ-PF score increased by level of global change (p < 0.001). Anchor-based methods identified an OPAQ-PF change of 10 at an individual patient level and 20 at a group level as meaningful to patients. CONCLUSIONS: The OPAQ-PF has confirmed unidimensionality and acceptable reliability, construct validity, and sensitivity to change in a recent fracture/no recent fracture osteoporosis sample.

Development of the Osteoporosis Assessment Questionnaire--physical Function (OPAQ-PF): an osteoporosis-targeted, patient-reported outcomes (PRO) measure of physical function.

UNLABELLED: We have developed a short, patient-reported outcome questionnaire--the Osteoporosis Assessment Questionnaire--Physical Function (OPAQ-PF)--that assesses the impact of osteoporosis on physical function. OPAQ-PF contains 15 items in three domains (mobility, physical positions, and transfers) and has content validity in osteoporosis patients with and without a history of fracture. INTRODUCTION: This paper describes the development of the Osteoporosis Assessment Questionnaire--Physical Function (OPAQ-PF), a patient-reported outcome (PRO) questionnaire based on OPAQ v.2.0 (60 items, 14 domains) that assesses the impact of osteoporosis on physical function. METHODS: OPAQ v.2.0 was administered to patients with osteoporosis. Item response theory methodology and clinical judgment were used to retain/eliminate items. The resulting instrument was modified during two sets of concept elicitation and cognitive debriefing interviews with osteoporosis patients. RESULTS: Item response theory-based analysis of OPAQ v.2.0 (n = 1,478) coupled with clinician input resulted in the generation of a 21-item, six-domain instrument with a frequency response format. Interview data from 32 participants were used to modify this version and led to generation of the final instrument, OPAQ-PF. This final version has a severity response format and contains 15 items in three domains (mobility, physical positions, and transfers) that group together to provide an overall assessment of physical function in patients with osteoporosis. Twenty-two of the 32 interview participants (69 %) had previously sustained a fracture. Symptoms occurred primarily in these patients. CONCLUSIONS: OPAQ-PF represents a brief, focused, PRO instrument that assesses physical function in patients with osteoporosis, specifically related to mobility, physical positions, and transfers. This questionnaire has content validity in osteoporosis patients who have, and have not, sustained a prior fracture.

Content validity of the Benign Prostatic Hyperplasia Impact Index (BII); a measure of how urinary trouble and problems associated with BPH may impact the patient.

AIMS: The objective of this qualitative interview study was to assess the content validity of the Benign Prostatic Hyperplasia Impact Index (BII) in a sample of men with signs and symptoms of Benign Prostatic Obstruction believed to be caused by benign prostatic hyperplasia (BPH lower urinary tract symptoms/BPH-LUTS) using concept elicitation (CE) and cognitive interviewing (CI) methods. METHODS: Fifty men with BPH-LUTS participated in the study; 27 completed CE interviews and 23 completed cognitive interviews. RESULTS: Patient's average age was 69 years with a mean duration of BPH-LUTS of 6.5 years. IPSS scores ranged from 8 to 33 (higher scores indicating greater symptom severity). Overall, the most frequent symptoms (prevalence of ≥ 75%) reported spontaneously or after further explanation were awakening from sleep, increased daytime voiding (frequency), urgent desire to void (urgency), slow stream, and feeling of incomplete bladder emptying. Symptoms primarily recognized in response to follow up probe questions with a prevalence of ≥ 40% included terminal dribble, splitting of urinary stream, intermittent stream, straining and post-micturition dribble. Especially bothersome [> 5 on the numerical rating scale (NRS) of 0-10] and frequent symptoms included urgency and awakening at night to void. Discomfort or pain while urinating and post-micturition dribble were equally bothersome though less frequent. Five BPH symptom-related impact themes were identified: coping, daily responsibilities, emotion, lifestyle and relationships, and sleep. CONCLUSIONS: The BII was found to be easily understood, does capture clinically relevant BPH impacts related to urinary trouble and problems, and does capture most of the important symptom-related impacts as described by participants in this study.

Development of a conceptual model of health-related quality of life for systemic lupus erythematosus from the patient's perspective.

AIMS: The aim of this study was to evaluate the impact of systemic lupus erythematosus (SLE) on the lives of patients in order to inform the development of a conceptual model. METHODS: Twenty-two participants with SLE (defined as meeting four of the 11 ACR criteria) were recruited for this study. Semi-structured, in-person interviews were conducted with each participant, exploring the symptoms experienced and the impact on the patient's life. Thematic analysis of interview transcripts was conducted in ATLAS.ti software to identify areas of impact and explore the interrelationships between concepts to inform the development of a conceptual model. RESULTS: Almost all participants were female (95%); the sample was diverse in terms of age (mean age of 45.5 years; age range of 20-60 years), ethnicity (59% black/African American) and disease duration. Commonly reported symptoms were pain, fatigue/tiredness and skin problems. Qualitative analysis revealed seven themes relating to the impact of SLE symptoms on patient's Health Related Quality of Life (HRQL): emotions, social, family and leisure activities, daily activities, cognition, appearance, employment activities and independence. The interrelationships between symptoms, impacts and symptom triggers are illustrated in a conceptual model. CONCLUSIONS: The conceptual model illustrates the wide-reaching impact of SLE symptoms on a patient's HRQL, and the potential broad impact of a treatment that improves SLE symptoms.

Expectations about and experiences with insulin therapy contribute to diabetes treatment satisfaction in insulin-naïve patients with type 2 diabetes.

AIM: The aim of this study was to investigate how patients' expectations about and experiences with insulin therapy contribute to diabetes treatment satisfaction. METHODS: The Expectations about Insulin Therapy (EAITQ) and the Experience with Insulin Therapy Questionnaires (EWITQ) were administered at baseline and end-point, respectively to insulin-naïve patients with type 2 diabetes in a randomised trial comparing treatment algorithms for inhaled insulin. Pearson correlation coefficients were calculated between EAITQ and EWITQ scores, patient characteristics and patient-reported outcomes measures. Wilcoxon Signed Rank test compared EAITQ and EWITQ item score distributions. Differences between EAITQ and EWITQ scores were calculated to categorize patients according to the extent to which their expectations were met by experiences (i.e. unmet, met, exceeded). RESULTS: EAITQ and EWITQ data were available for 240 patients (61% male, mean age 58 years, mean diabetes duration 10 years, mean baseline HbA(1c) 8.4%). Increasingly positive expectations were significantly associated with greater self-efficacy; greater levels of positive experiences were significantly associated with greater positive expectations, shorter diabetes duration, less symptom distress, greater well-being, self-efficacy and diabetes treatment satisfaction. Overall, patients' experiences with inhaled insulin therapy were significantly more positive than their expectations: 58% patients' experiences exceeded expectations, 29% patients' experiences met expectations and 13% patients' experiences did not meet expectations. Post hoc tests indicated that treatment satisfaction scores differed among these groups (all p < 0.01). CONCLUSION: Expectations may not independently impact treatment satisfaction, but the relationship with experiences significantly contributes to it. The EAITQ and EWITQ may be useful tools for clinicians to better understand patients' expectations about and experiences with insulin therapy.

Initial clinical experience with a wearable controller for the Novacor left ventricular assist system.

The Novacor left ventricular assist system (LVAS), an implanted electromechanically driven blood pump, has been used in an ongoing clinical trial as a bridge to cardiac transplantation since 1984. The initial configuration included a console based extracorporeal controller. Because patients supported by the device usually become rehabilitated and highly mobile, a wearable control system was developed for the ambulatory patient. Ergonomically designed for portability, comfort, and appearance, it offers the recipient greater mobility, improved self-image, and an enhanced quality of life. This wearable control system consists of a microprocessor based compact controller that drives the implanted pump/drive unit in synchronous counterpulsation to the native heart. Main and reserve rechargeable power packs, each incorporating a "smart" monitoring circuit with charge-level display and alarm, are capable of supporting the pump for as long as 7 hr. An LVAS monitor can be connected to the controller for device monitoring and adjustment or as a power supply in lieu of the main power pack. Clinical evaluation in patients with end-stage heart disease followed the same protocol as the console study. By April 4, 1994, 41 patients had been supported by the wearable system, including 9 patients currently being supported. Mean duration of use was 51 days (range, 1.5-143+ days), compared with 42 days for 170 console patients (range, 0-370 days). Survival to transplant was 66%, which was similar to the survival (60%) for the patients using the console. Post-transplant survival was 100%, compared with 90% for console patients (not significantly different). After recovering from implant surgery and pre-implant morbidity, device recipients had considerable freedom and mobility and were able to move freely within and outside the hospital. Recipients could readily switch between monitored and untethered operation and could manage power pack replacement and recharging.