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Purpose Establishing a meaningful within-individual change (MWIC) threshold is a key aspect for interpreting scores used as endpoints for evaluating treatment benefit. A new patient-reported outcome (PRO), a sleep disturbance numerical rating scale (SD NRS), was developed in adults and adolescents with moderate-to-severe atopic dermatitis (AD). This research aims to establish a MWIC threshold of the SD NRS score in the context of a drug development program. Methods An explanatory sequential mixed-methods design was used to address the research objective. This mixed-methods design used phase IIb data and a stand-alone qualitative study. Quantitative anchor-based and distribution-based approaches supported by qualitative-based approaches were conducted, and results were triangulated to determine preliminary MWIC thresholds of the SD NRS score. Results Triangulation of results from both quantitative and qualitative approaches suggested that a 2- to 6-point decrease in the SD NRS score change constitutes a preliminary range of MWIC threshold estimates. Conclusion This research determined MWIC threshold estimates for the SD NRS score in both adolescents and adults with moderate-to-severe AD using an explanatory sequential mixed-methods design. This mixed-methods design provides interesting insights for establishing MWIC thresholds of a PRO score in the context of a drug development program.

Atopic dermatitis (AD) is associated with eczematous lesions, pruritus, pain, and sleep disturbance, which may negatively impact mental health over time.To determine the predictors and longitudinal course of depressive symptoms in adults with AD.A prospective, dermatology practice-based study was performed (N = 695). AD signs, symptoms, and severity and patient health questionnaire-9 (PHQ-9) were assessed.At baseline, of the 695 participants, 454 (65.32%) had minimal, 139 (20.00%) had mild, 57 (8.20%) had moderate, 27 (3.88%) had moderately severe, and 8 (2.59%) had severe depression. Most had fluctuating levels of depressive symptoms. Feeling bad, thoughts of self-harm, difficulty concentrating, and slow movement were most persistent. Predictors of persistent depression included older age, non-White race, male sex, public or no insurance, more severe itch, skin pain, facial erythema, nipple eczema, sleep disturbance, and presence of pityriasis alba.Single center study.Depressive symptoms are closely related to and fluctuate with AD severity over time. Improved control of AD signs and symptoms, particularly itch, may secondarily improve mental health.

La photothèque Hachette Livre, aujourd’hui classée patrimoine historique national et riche d’environ 700 000 images, s’est constituée sur plus d’un siècle par l’achat de tirages, de documents divers et de collections anciennes, ainsi que par une production photographique en interne, le tout destiné à l’édition de livres et revues illustrés. L’étude de ce fonds exemplaire permet de restituer son histoire et parallèlement de mettre à jour les traces perdues de son fonctionnement, à travers l’organisation des services qui se sont succédé au cours des années, impliquant le portrait des acteurs de sa création, de son développement et de sa gestion. Ainsi se précisent tous les métiers et pratiques engagés dans les différents processus d’acquisition, de production, de conservation, de documentation, de diffusion et d’utilisation de ces images, et s’esquisse peu à peu le tableau des archives photographiques heureusement conservées du plus grand groupe éditorial français.

Prurigo nodularis (PN) is an understudied, pruritic inflammatory skin disease. Little is known about the effect of PN on quality of life and its associated economic burden.To quantify the impact of PN on quality of life and its economic implications.A cohort study of PN patients (n = 36) was conducted using the Health Utilities Index Mark 3 questionnaire. Control data from US adults (n = 4187) were obtained from the 2002-2003 Joint Canada/United States Survey of Health. Quality-adjusted life year loss and economic costs were estimated by comparing the Health Utilities Index Mark 3 scores of the PN patients with those of the controls.The PN patients had lower overall health performance compared to the controls, (mean ± SE, 0.52 ± 0.06 vs 0.86 ± 0.003, respectively, P .001). In multivariable regression, PN was found to be associated with worse health performance (coefficient -0.34, 95% CI [-0.46 to -0.23]), most prominent in the pain subdomain (coefficient -0.24, 95% CI [-0.35 to -0.13]). This correlated to an average of 6.5 lifetime quality-adjusted life years lost per patient, translating to an individual lifetime economic burden of $323,292 and a societal burden of $38.8 billion.These results demonstrate that PN is associated with significant quality-of-life impairment, similar to the level of other chronic systemic conditions. PN is also associated with a substantial individual economic burden, emphasizing the necessity of research on effective treatment options.

BACKGROUND Prurigo nodularis (PN) is associated with a variety of systemic comorbidities, including infectious diseases such as HIV and viral hepatitis. There are limited data on other infectious disease comorbidities in patients with PN. AIM To characterize infectious disease hospitalizations among patients with PN and the associated cost burden. METHODS We searched the 2016-2017 National Inpatient Sample, a cross-sectional sample of 20% of all US hospitalizations, for infectious disease hospitalizations among patients with PN. Associations of PN with infections and related costs were determined using multivariable logistic and linear regression, adjusting for age, race, sex and insurance type. RESULTS PN was associated with any infection overall (OR = 2.98, 95% CI 2.49-3.56), and with HIV, cutaneous, hepatobiliary, central nervous system, bacterial, viral and fungal/parasitic infections and for sepsis. Patients with PN had a higher mean cost of care (US$11 667 vs. US$8893, P

Itch is a complex symptom that is both common and burdensome in atopic dermatitis (AD). Yet, little is known about the longitudinal course of itch in AD. A prospective, dermatology practice-based study was performed of adults with AD (n = 463). Patients were assessed at baseline and approximately 6, 12, 18 and 24 months. Itch was assessed using Numeric Rating Scale (NRS) average and worst-itch scores, and frequency of itch in the past week. Repeated-measures regression models were constructed to examine itch over time. Overall, 31.5% and 22.5% had moderate (4-6) or severe (7-10) NRS average-itch scores; 27.4% and 36.4% had moderate (4-6) or severe (7-10) NRS worst-itch scores; 12.7% and 62.0% had itch from eczema 3-4 and ≥ 5 days in the past week; 27.4% and 45.1% reported sometimes and often/almost always having itch, respectively. Among patients with baseline moderate (4-6) or severe (7-10) NRS average-itch scores, 21.2% and 16.3% continued to have moderate or severe scores at ≥ 1 follow-up visits. In repeated-measures regression models, persistent NRS average-itch scores were associated with baseline NRS average-itch [adjusted β (95% CI): 0.75 (0.68, 0.82)] and food allergy [- 0.45 (- 0.84, - 0.07)]. Persistent NRS worst-itch was associated with baseline worst-itch NRS [0.73 (0.66, 0.80)] and Medicaid insurance [1.06 (0.17, 1.94)]. AD patients had a heterogeneous longitudinal course with fluctuating and complex overlapping patterns of average- and worst-itch intensity, and frequency.

Introduction: Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by intensely pruritic, hyperkeratotic nodules distributed on the trunk and extensor surfaces of the extremities. PN has a profoundly negative impact on sleep and quality of life in patients with PN. There are currently no U.S. Food and Drug Administration-approved agents and patients are often recalcitrant to current therapies, highlighting the importance of further research into this severely debilitating condition. Areas covered: A PubMed search was conducted to find available literature on the pathophysiology and clinical management of PN. In this review article, we discuss the current understanding of the pathophysiology, recommended diagnostic approach, and treatment options available for PN. Expert opinion/commentary: PN is an extremely difficult condition to treat, because there is a lack of effective therapies available due to our limited understanding of its pathophysiology. Currently, available treatment options are often multimodal due to the intersection of neuroimmune etiologic factors in the pathogenesis of PN. Fortunately, as our knowledge of PN expands, novel treatments targeting specific molecular biomarkers of PN are emerging, providing hope to this long-suffering patient population.

Background Little is known about the measurement properties of Patient-Oriented Scoring Atopic Dermatitis (PO-SCORAD) in adults with atopic dermatitis (AD). Even less is known about how PO-SCORAD performs compared with the Patient-Oriented Eczema Measure (POEM). Objective To examine the measurement properties of PO-SCORAD and compare them with those of POEM. Methods A prospective dermatology practice–based study of 291 patients with AD (age range, 18-72 years). Results PO-SCORAD and POEM were moderately correlated with each other (Spearman ρ = 0.56) and had weak-moderate correlations with the Numeric Rating Scale (NRS) worst itch and average itch, Dermatology Life Quality Index (DLQI), ItchyQOL, Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance (SD) and Sleep-Related Impairment (SRI), Patient Health Questionnaire-9 (PHQ-9), and Eczema Area and Severity Index (EASI) (P Conclusion PO-SCORAD and POEM had good construct and cross-cultural validity, reliability, and responsiveness in adults with AD and were feasible for use in clinical trials and practice. However, POEM had better measurement properties than PO-SCORAD.

Sleep disturbance (SD) is common in atopic dermatitis (AD). We examined the longitudinal course of SD and relationship with itch in AD patients.A prospective, dermatology practice-based study was performed (N = 1295) where patients were assessed at baseline and follow-up visits.At baseline, 16.9% of the patients had severe SD based on Patient-Reported Outcomes Information System (PROMIS) SD T scores, 19.1% had difficulty falling asleep, 22.9% had difficulty staying asleep, and 34.2% had SD from AD. A total of 31.4% of the patients with difficulty staying asleep at baseline experienced persistent difficulties (for 3 follow-ups or more). Only 17.7% with baseline difficulty falling asleep had persistent disturbance. Despite significant fluctuation in sleep scores, SD generally improved over time. Of the patients facing baseline SD from AD, 31.5% experienced SD at the first visit, and only 12.3% experienced persistent SD at the second follow-up visit. Predictors of increased PROMIS sleep-related impairment T scores over time included baseline PROMIS sleep-related impairment T scores (0.74 [0.68-0.80]), having 3 to 6 nights of itch (2.22 [0.85-3.59]), and severe/very severe AD (4.40 [2.60-6.20]).A significant proportion of adult AD patients, particularly those with moderate-severe AD and frequent itch, had baseline SD. Although sleep scores generally improved over time, many patients experienced a fluctuating or persistent course.

Prurigo nodularis is a debilitating skin condition that is classified as rare by the Genetic and Rare Diseases Information Center (GARD) and the National Organization for Rare Diseases (NORD). There are currently no estimates of the prevalence of prurigo nodularis in England.We aimed to address this data gap by describing the epidemiology of prurigo nodularis in a representative dataset derived from the English National Health Service.The study utilized data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics inpatient data. Patients with a diagnosis of prurigo nodularis were selected by clinical code in the primary care or inpatient datasets. Case definition was based on a minimum of two distinct diagnoses to maximize specificity. Point prevalence was calculated for the midpoint of 2018 and incidence rates from 2008 to 2018 were presented. For those classified as incident cases, demographic and clinical characteristics were reported. In sensitivity analyses the case definition was modified to relax the multiple diagnosis criteria and to restrict cases to those diagnosed within a maximum of 4 or 10 years of the midpoint prevalence date.Overall, 11 656 patients within the dataset had at least one prurigo nodularis diagnosis. Following application of the relevant inclusion criteria, 2743 patients formed the point prevalent cohort; the estimated prevalence was 3·27 patients per 10 000 population [95% confidence interval (CI) 3·15-3·40]. In sensitivity analyses the estimated prevalence ranged from 2·24 (95% CI 2·14-2·34) to 6·98 (95% CI 6·80-7·16). Incidence over the study period was 2·88 per 100 000 patient-years. Comorbidity was relatively high in this population, notably for atopic dermatitis (52·2%), depression (41·1%) and anxiety (35·4%).This study supports the NORD/GARD classification of prurigo nodularis as a rare disease with a prevalence of 3·27 patients per 10 000 population, which equates to 18 471 patients living with the disease in England in 2018. The relatively high prevalence of comorbidity observed for these patients may increase the complexity of management.

Background Patient-Reported Outcomes Measurement Information System Global Health (PGH) was validated to assess health-related quality of life in several diseases. Little is known about its measurement properties in adult atopic dermatitis. Objective Examine the measurement properties of PGH in adult atopic dermatitis. Methods A prospective dermatology practice–based study of 994 atopic dermatitis patients (18-97 years). Results PGH physical and mental health 4-item and abridged 2-item T scores, as well as mapped EuroQol-5D score, showed strong to very strong correlation with one another and moderate to strong Spearman correlations with Patient-Oriented Scoring Atopic Dermatitis, Patient-Health Questionnaire–9, Patient-Reported Outcomes Measurement Information System sleep disturbance and related impairment, Eczema Area and Severity Index, objective Scoring Atopic Dermatitis; and weak to moderate correlations with Patient Oriented Eczema Measure, numeric rating scale worst itch and average itch, and Scoring Atopic Dermatitis. The Dermatology Life Quality Index (DLQI) had stronger correlations with Patient Oriented Eczema Measure, Patient-Oriented Scoring Atopic Dermatitis, numeric rating scale worst itch and average itch, Eczema Area and Severity Index, and Scoring Atopic Dermatitis, but weaker correlations with Patient-Health Questionnaire–9 and Patient-Reported Outcomes Measurement Information System sleep disturbance and related impairment (convergent/divergent validity). PGH and DLQI scores had similarly poor ability to differentiate between levels of self-reported global atopic dermatitis severity (known-groups validity). No floor or ceiling effects were observed. No PGH or DLQI items had differential item functioning by demographics. PGH and DLQI scores showed fair to good responsiveness. Finally, PGH and DLQI showed similarly good test-retest reliability. Limitations Single-center study. Conclusion PGH scores had sufficient validity and reliability to assess health-related quality of life in atopic dermatitis.

Background Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by intense pruritus, but information on patient experience and impact on quality of life (QoL) remains understudied. Aim To characterize disease characteristics and QoL in a global sample of patients with PN. Methods An anonymous survey was distributed via patient support groups for PN. Results In total, 231 members responded to the survey. The majority of respondents reported itch localized both to nodules and to intervening skin (67.0%). Associated symptoms included prickling, pain, stinging and burning. The extensor lower legs (69% right, 67.3% left) and flexor forearms (66.1% right, 62% left) were the most common sites of itch. Participants reported frequent healthcare utilization, with 36.3% visiting a doctor ≥ 10 times in the past year. Physician-diagnosed anxiety (45.4%), depression (16.4%) and the atopic triad (18.7%) were commonly reported. Patients with PN had mean scores of 16.4, 11.6 and 16.8 on the Dermatology Life Quality Index, Pittsburgh Sleep Quality Index and 5-Dimensions Itch, respectively. Conclusions Severe pruritus with accompanying pain, stinging and burning is characteristic of PN, with the majority of patients experiencing itch in both nodular and interlesional skin. Patients further report decreased QoL scores and impaired sleep. Patient experiences should guide future management of PN.

Patients with atopic dermatitis (AD) have heterogeneous clinical phenotypes, including different combinations of itch and lesional severity. Little is known about the characteristics and course of these subtypes.To determine the characteristics, associations, burden, and course of patients with AD using combined itch and lesional severity.A prospective practice-based study was performed using questionnaires and physical examination (n=592). AD subsets were defined using verbal rating scale for average itch combined with either eczema area and severity index, objective-scoring atopic dermatitis (SCORAD), or validated investigator's global assessment as follows: mild-moderate itch and lesions (MI-ML), mild-moderate itch and severe lesions (MI-SL), severe itch and mild-moderate lesions (SI-ML), and severe itch and lesions (SI-SL).At baseline, there were only weak-moderate correlations of numerical rating scales for worst itch or average itch or SCORAD itch with eczema area and severity index, objective-SCORAD, body surface area, and validated investigator's global assessment (Spearman's rho = 0.32-0.62). Most patients had MI-ML (59.4%-62.3%), followed by SI-ML (21.3%-29.1%), SI-SL (6.0%-12.9%), and MI-SL (3.8%-6.4%). Patients with SI-SL, followed by SI-ML and MI-SL, described their AD as being more severe overall and had worse impairment in sleep, mental health, and quality of life. However, those with MI-SL or SI-SL were far more likely to be classified as severe by a physician (multivariable logistic and linear regression, P.005 for all). Baseline MI-SL, SI-ML, and SI-SL were associated with similar longitudinal courses over time and more AD flares and itch triggers than MI-ML.Combined itch and lesional severity seem to describe unique AD phenotypes. Further studies are needed to confirm these findings and understand the optimal treatments for these groups.

BACKGROUND: Multiple clinician-reported outcome measures exist for atopic dermatitis (AD) severity. However, there is no gold standard for use in clinical practice. OBJECTIVES: To determine the measurement properties of the product of validated Investigator's Global Assessment for AD (vIGA) and body surface area (BSA) overall or divided into six categories (cBSA: 0%/0.1

Background Few outcome measures were validated for assessing depressive symptoms in AD. Patient Health Questionnaire-9 (PHQ9) and the abridged PHQ2 are established patient-reported outcome measures of depressive symptoms. Objective We sought to examine the measurement properties of PHQ9 and PHQ2 in adult AD. A prospective dermatology-practice based study of 458 AD patients (age 18-97 years) was conducted. Results PHQ9 strongly correlated with Dermatology Life Quality Index, Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep-Disturbance and Sleep-Related Impairment, and PROMIS Itch Questionnaire Mood and Sleep (PIQ-MS), and moderately correlated with Patient-Oriented Eczema Measure, Numeric Rating Scale (NRS) average-itch, NRS-sleep, Eczema Area and Severity Index, Scoring AD and Rajka-Langeland scores. PHQ2 had significantly weaker correlations than PHQ9 with PROMIS SD, SRI and PIQ-MS, but similar correlations with other outcomes. PHQ9 and PHQ2 had good discriminant validity. Changes from baseline in PHQ9 and PHQ2 were poorly or weakly correlated with changes of the other outcome measures. There was no differential item functioning of PHQ items. PHQ9 showed good reliability (intraclass correlation coefficient range: 0.80-0.87). PHQ2 had slightly lower reliability (0.76-0.82). Conclusions PHQ9 and PHQ2 had similar measurement properties, but PHQ2 was more feasible to assess depressive symptoms in AD.

Background Atopic dermatitis (AD) is associated with heterogeneous triggers of itch, which may affect AD course and severity. Objective To characterize the triggers of itch in adult AD. Methods This was a prospective dermatology practice–based study using questionnaires and evaluation by a dermatologist (n = 587). Thirteen itch triggers were assessed using the patient-reported outcomes measurement information system Itch-Triggers. Results Overall, 381 (64.9%) patients reported greater than or equal to 1 itch trigger in the past week and 212 (36.1%) reported greater than or equal to 3 itch triggers. The most commonly reported triggers were stress (35.4%), sweat (30.5%), weather change (24.7%), dry air (24.4%), and heat (24.0%). In multivariable Poisson regression models, the number of itch triggers was associated with more severe patient-reported global AD severity, Numeric Rating Scale worst itch, Patient-Oriented Eczema Measure, Scoring Atopic Dermatitis sleep, Numeric Rating Scale skin pain, Eczema Area and Severity Index, and objective Scoring Atopic Dermatitis. The seasonality of AD was associated with distinct itch triggers. In multivariable logistic regression models, the number of itch triggers was associated with less than or equal to 3 months of AD remission during the year, greater than or equal to 2 AD flares, and AD being worse during some seasons. Four patterns of itch triggers were identified using latent class analysis, each associated with different clinical characteristics. Conclusion Itch triggers are common and affect the course of AD. Itch triggers are an important end point to assess in patients with AD.

Itch is a complex symptom that is both common and burdensome in atopic dermatitis (AD). Yet, little is known about the longitudinal course of itch in AD. A prospective, dermatology practice-based study was performed of adults with AD (n = 463). Patients were assessed at baseline and approximately 6, 12, 18 and 24 months. Itch was assessed using Numeric Rating Scale (NRS) average and worst-itch scores, and frequency of itch in the past week. Repeated-measures regression models were constructed to examine itch over time. Overall, 31.5% and 22.5% had moderate (4-6) or severe (7-10) NRS average-itch scores; 27.4% and 36.4% had moderate (4-6) or severe (7-10) NRS worst-itch scores; 12.7% and 62.0% had itch from eczema 3-4 and ≥ 5 days in the past week; 27.4% and 45.1% reported sometimes and often/almost always having itch, respectively. Among patients with baseline moderate (4-6) or severe (7-10) NRS average-itch scores, 21.2% and 16.3% continued to have moderate or severe scores at ≥ 1 follow-up visits. In repeated-measures regression models, persistent NRS average-itch scores were associated with baseline NRS average-itch [adjusted β (95% CI): 0.75 (0.68, 0.82)] and food allergy [- 0.45 (- 0.84, - 0.07)]. Persistent NRS worst-itch was associated with baseline worst-itch NRS [0.73 (0.66, 0.80)] and Medicaid insurance [1.06 (0.17, 1.94)]. AD patients had a heterogeneous longitudinal course with fluctuating and complex overlapping patterns of average- and worst-itch intensity, and frequency.

Prurigo nodularis is an itchy skin disease with unknown epidemiology. This study aimed to describe the epidemiology of prurigo nodularis compared with that of psoriasis. The German sickness fund claims database, with 2,783,175 continuously insured patients, included 1,720 patients diagnosed with prurigo nodularis and 51,390 with psoriasis. Patients with prurigo nodularis were averagely 8 years older than psoriasis patients and more often were women (p < 0.001). Annual incidence was a constant 0.02% in prurigo nodularis, and decreased steadily from 0.53 to 0.42% in psoriasis; cumulative incidence was 0.1% for prurigo nodularis and 1.9% for psoriasis. Prevalence was 0.1% for prurigo nodularis and 4.7% for psoriasis, with a 1-year mortality of 5.4% for prurigo nodularis and 1.2% for psoriasis (p < 0.001). The most frequent pre-existing comorbidities in patients with prurigo nodularis were inflammatory dermatoses and depression. This epidemiological study found a low prevalence of prurigo nodularis, manifesting different demographics and comorbidities compared with psoriasis.

Background Little is known about the longitudinal course of adult atopic dermatitis (AD) lesional severity and extent in clinical practice. Objective To determine the longitudinal course of AD in clinical practice. Methods A prospective, dermatology practice–based study was performed (n = 400). Patients were assessed at baseline and approximately 6, 12, 18, and 24 months by eczema area and severity index (EASI) and objective–scoring atopic dermatitis (objective-SCORAD). Multivariable repeated measures linear regression models were constructed to evaluate AD severity over time. Results Overall, 36.2% and 18.2% of patients had moderate (6.0-22.9) or severe (23.0-72.0) EASI scores at any visit, respectively. Similarly, 29.0% and 26.4% of patients had moderate (24.0-37.9) or severe (38.0-83.0) objective-SCORAD scores at any visit, respectively. Among patients with baseline moderate (6.0-22.9) or severe (23.0-72.0) EASI scores, 25.0% and 18.6% continued to have moderate or severe scores at 1 or more follow-up visits, respectively. Similarly, among patients with baseline moderate (24.0-37.9) or severe (38.0-83.0) objective-SCORAD scores, 22.6% and 24.5% continued to have moderate or severe scores at 1 or more follow-up visits, respectively. In longitudinal regression models, EASI was significantly associated with body surface area (adjusted β [95% confidence interval]: 0.16 [0.09-0.23]) and edema/papulation (2.31 [0.19-4.43]). In addition, objective-SCORAD was significantly associated with body surface area (0.12 [0.04-0.21]), edema/papulation (4.69 [2.05-7.32]), and scratch (3.34 [0.45-6.24]) over time. Conclusion AD lesional severity has a heterogeneous longitudinal course. Many patients had fluctuating lesional severity scores over time. A minority of patients had persistently moderate or severe lesions over time. Most patients with moderate-severe disease at baseline were unable to achieve persistent lesional clearance.

Background Multiple atopic dermatitis (AD) severity scales exist, with no gold standard for use in clinical practice. Objectives To determine the measurement properties of the Rajka-Langeland score and compare it with other clinician-reported outcomes in adults and children with AD. Methods We performed a prospective dermatology practice-based study using questionnaires and evaluation by a dermatologist (n = 427). Results Rajka-Langeland had good concurrent validity with the Eczema Area and Severity Index (Spearman rho = 0·63), SCORing AD (SCORAD) (rho = 0·61), objective-SCORAD (rho = 0·52) and body surface area (rho = 0·51); good convergent validity with the numeric rating scale average-itch (rho = 0·60) and worst-itch (rho = 0·59), Patient-Oriented Eczema Measure (rho = 0·57), Dermatology Life Quality Index (rho = 0·53), Patient-Reported Outcomes Measurement Information System Itch Questionnaire (rho = 0·35-0·55) in adults and/or children; fair discriminant validity for patient- and physician-reported global AD severity; good responsiveness to change of severity of AD and itch; good reliability; internal consistency; with no floor or ceiling effects. Interpretability bands (3, clear/almost clear; 4-5, mild; 6-7, moderate; 8-9, severe) and minimal clinically important difference (1 point) were established. Conclusions The Rajka-Langeland score showed good construct validity, reliability, internal consistency and responsiveness in adults and children with AD.

Background Atopic dermatitis (AD) is associated with itch, pain, and sleep disturbance, all of which may contribute toward cognitive dysfunction. Objective To determine the relationship of AD severity and cognitive function in adults. Methods We performed a prospective dermatology practice-based study using questionnaires and evaluation by a dermatologist (n = 386). Cognitive function was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Cognitive Function 8-item Short-Form. Results At baseline, 118 patients (58.1%) reported ≥1 symptoms of cognitive dysfunction in the past 4 weeks, with 29 (14.3%) having mild, 11 (5.4%) moderate, and 4 (2.0%) severe PROMIS Cognitive Function T-scores. In propensity score-weighted regression models, PROMIS Cognitive Function T-scores were inversely associated with patient-reported global AD severity, Patient Oriented Eczema Measure (POEM), Numeric Rating Scale worst itch and skin pain, SCORing Atopic Dermatitis (SCORAD)-sleep, POEM-sleep, Eczema Area and Severity Index, and SCORAD, with stepwise decreases of cognitive function with worsening AD severity. At all AD severity levels, cognitive dysfunction was associated with increased Dermatology Life Quality Index and ItchyQoL scores. Changes from baseline in PROMIS Cognitive Function T-scores were weakly to moderately inversely correlated with changes from baseline in multiple AD outcomes. Limitations Single-center study without non-AD controls. Conclusion Cognitive dysfunction is associated with AD severity. Cognitive function may be an important end point for monitoring treatment response in AD.

The optimal approaches for monitoring sleep disturbances in adults with atopic dermatitis (AD) is not established. Multiple patient-reported outcome measures for AD and itch have sleep-related items. These items have not been validated previously.Assess the measurement properties of sleep-related items from the Patient-Oriented Eczema Measure (POEM), SCORing AD (SCORAD), 5-dimensions of itch (5D), and ItchyQOL in adults with AD.We performed a prospective dermatology practice-based study using questionnaires and evaluation by a dermatologist (n = 115).There was modest overlap and weak-moderate concordance of responses to the different assessments. Regarding concurrent validity, POEM-sleep, SCORAD-sleep, 5D-sleep, and ItchyQOL-sleep showed moderate correlations with each other. Regarding convergent validity, all items showed moderate correlation with total POEM, but weak correlations with Eczema Area and Severity Index (EASI), objective and total SCORAD, moderate to strong correlations with mean ItchyQOL and Dermatology Life Quality Index (DLQI), but poor or no significant correlation with Numeric Rating Scale (NRS) for worst or average itch. Regarding discriminant validity, all items showed significant and stepwise increases with increasing self-reported and physician-reported AD severity (Kruskal-Wallis, P.01 for all). Floor effects were observed for POEM-sleep (n = 53, 46.1%), SCORAD-sleep (n = 28, 24.4%), 5D-sleep (n = 41, 35.7%), and ItchyQOL-sleep (n = 33, 28.7%); no ceiling effects were observed. Change in sleep-related item scores showed moderate strong correlations with change in POEM, 5Ditch, mean ItchyQOL, DLQI, objective and total SCORAD, and EASI, but inconsistent correlations with change of itch severity.Sleep-related items from POEM, SCORAD, 5D and ItchyQOL showed good validity and responsiveness to monitor sleep disturbances in adult AD patients.

Introduction Well- or moderately differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are often slow-growing, and some patients with unresectable, asymptomatic, non-functioning tumors may face the choice between watchful waiting (WW), or somatostatin analogues (SSA) to delay progression. We developed a comprehensive multi-criteria decision analysis (MCDA) framework to help patients and physicians clarify their values and preferences, consider each decision criterion, and support communication and shared decision-making. Methods The framework was adapted from a generic MCDA framework (EVIDEM) with patient and clinician input. During a workshop, patients and clinicians expressed their individual values and preferences (criteria weights) and, on the basis of two scenarios (treatment vs WW; SSA-1 [lanreotide] vs SSA-2 [octreotide]) with evidence from a literature review, expressed how consideration of each criterion would impact their decision in favor of either option (score), and shared their knowledge and insights verbally and in writing. Results The framework included benefit-risk criteria and modulating factors, such as disease severity, quality of evidence, costs, and constraints. Overall and progression-free survival being most important, criteria weights ranged widely, highlighting variations in individual values and the need to share them. Scoring and considering each criterion prompted a rich exchange of perspectives and uncovered individual assumptions and interpretations. At the group level, type of benefit, disease severity, effectiveness, and quality of evidence favored treatment; cost aspects favored WW (scenario 1). For scenario 2, most criteria did not favor either option. Conclusions Patients and clinicians consider many aspects in decision-making. The MCDA framework provided a common interpretive frame to structure this complexity, support individual reflection, and share perspectives. Funding Ipsen Pharma. Electronic supplementary material The online version of this article (10.1007/s12325-017-0653-1) contains supplementary material, which is available to authorized users.

Background Cervical dystonia (CD) involves painful involuntary contraction of the neck and shoulder muscles and abnormal posture in middle-aged adults. Botulinum neurotoxin type A (BoNT-A) is effective in treating CD but little is known about its associated cost-effectiveness. Objective To evaluate the cost-effectiveness of abobotulinumtoxinA for treating CD from the UK payer perspective. Methods A Markov model was developed to evaluate the cost-effectiveness of abobotulinum-toxinA versus best supportive care (BSC) in CD, with a lifetime horizon and health states for response, nonresponse, secondary nonresponse, and BSC in patients with CD (mean age: 53 years; 37% male). Clinical improvement measured using Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) was mapped to utility using data from a randomized trial of abobotulinumtoxinA. Health care resource use, costs, and other inputs were from the British National Formulary, Personal Social Services Research Unit, published literature, or expert opinion. Costs and outcomes were discounted at 3.5% per annum. Results In the base case, the incremental lifetime quality-adjusted life-years (QALYs) gained from abobotulinumtoxinA arm versus BSC was 0.253 per patient, whereas the incremental cost was £7,160, leading to an incremental cost-effectiveness ratio (ICER) of £30,468 per QALY. One-way sensitivity analyses showed that these results were sensitive to the proportion of responders to abobotulinumtoxinA at first injection, duration between injections, the number of reinjections allowed among primary nonresponders, and any difference in baseline TWSTRS value between the BSC and abobotulinumtoxinA arms. Probabilistic sensitivity analysis showed that abobotulinumtoxinA was cost-effective 46% and 49% of times at thresholds of £20,000 and £30,000 per QALY, respectively. Scenarios are considered including vial-sharing, productivity losses, secondary response/nonresponse at subsequent injections, 5-year time horizon, and alternative reinjection intervals for BoNT-As produced ICERs ranging from cost-saving to £40,777 per QALY, versus BSC. Conclusion AbobotulinumtoxinA was found to be cost-effective in treating adults with CD, at acceptable willingness-to-pay thresholds in the UK.

Little is known about the measurement properties of Patient-Oriented Scoring Atopic Dermatitis (PO-SCORAD) in adults with atopic dermatitis (AD). Even less is known about how PO-SCORAD performs compared with the Patient-Oriented Eczema Measure (POEM).To examine the measurement properties of PO-SCORAD and compare them with those of POEM.A prospective dermatology practice-based study of 291 patients with AD (age range, 18-72 years).PO-SCORAD and POEM were moderately correlated with each other (Spearman ρ = 0.56) and had weak-moderate correlations with the Numeric Rating Scale (NRS) worst itch and average itch, Dermatology Life Quality Index (DLQI), ItchyQOL, Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance (SD) and Sleep-Related Impairment (SRI), Patient Health Questionnaire-9 (PHQ-9), and Eczema Area and Severity Index (EASI) (P.001). POEM had significantly stronger correlations with DLQI, ItchyQOL, and EASI than did PO-SCORAD. PO-SCORAD and POEM had fair discriminant validity. Changes from baseline in PO-SCORAD and POEM were moderately correlated with each other; were weakly to strongly correlated with NRS worst itch and average itch, DLQI, ItchyQOL, PROMIS SD, PROMIS SRI, PHQ-9, and EASI; and had good test-retest reliability. There was no differential item functioning of items or floor or ceiling effects for PO-SCORAD or POEM. The thresholds for meaningful change for PO-SCORAD and POEM were -15.5 and -5.0, respectively. Median completion times for PO-SCORAD and POEM were 3 minutes and 1 minute, respectively.PO-SCORAD and POEM had good construct and cross-cultural validity, reliability, and responsiveness in adults with AD and were feasible for use in clinical trials and practice. However, POEM had better measurement properties than PO-SCORAD.

Most patients with mycosis fungoides are diagnosed with early-stage disease. However, prevalence of early-stage disease is unknown, and evidence of its burden is scarce. The aim of this study is to estimate the prevalence of early-stage mycosis fungoides, how long patients live with early-stage disease and to characterise these patients. Data were obtained from 4 key publications and from US cancer registries (Surveillance, Epidemiology and End Results Program; SEER). The derived incidence of early-stage mycosis fungoides was 0.26/100,000 (UK), 0.29/100,000 (US) and 0.38/100,000 (US-SEER) and the prevalence was 4.8/100,000 (UK), 5.2/100,000 (US) and 6.6/100,000 (US-SEER). Early-stage disease may last for 18 years. From SEER registries, 3,132 were diagnosed at early stage (mostly stage IA). Median age at diagnosis was 58 years. Compared with stage IA, the relative risk of death was 1.3 for stage IB and 3.5 for stage IIA. We confirm the rarity of early-stage mycosis fungoides, a differential prognosis and the potential for elevated burden of disease.

Background Patients with atopic dermatitis (AD) have heterogeneous clinical phenotypes, including different combinations of itch and lesional severity. Little is known about the characteristics and course of these subtypes. Objective To determine the characteristics, associations, burden, and course of patients with AD using combined itch and lesional severity. Methods A prospective practice-based study was performed using questionnaires and physical examination (n=592). AD subsets were defined using verbal rating scale for average itch combined with either eczema area and severity index, objective—scoring atopic dermatitis (SCORAD), or validated investigator's global assessment as follows: mild-moderate itch and lesions (MI-ML), mild-moderate itch and severe lesions (MI-SL), severe itch and mild-moderate lesions (SI-ML), and severe itch and lesions (SI-SL). Results At baseline, there were only weak-moderate correlations of numerical rating scales for worst itch or average itch or SCORAD itch with eczema area and severity index, objective-SCORAD, body surface area, and validated investigator's global assessment (Spearman's rho = 0.32-0.62). Most patients had MI-ML (59.4%-62.3%), followed by SI-ML (21.3%-29.1%), SI-SL (6.0%-12.9%), and MI-SL (3.8%-6.4%). Patients with SI-SL, followed by SI-ML and MI-SL, described their AD as being more severe overall and had worse impairment in sleep, mental health, and quality of life. However, those with MI-SL or SI-SL were far more likely to be classified as severe by a physician (multivariable logistic and linear regression, P Conclusion Combined itch and lesional severity seem to describe unique AD phenotypes. Further studies are needed to confirm these findings and understand the optimal treatments for these groups.

Objective: Post-stroke spasticity (PSS) is a common complication following stroke. This study describes the differences in healthcare resource utilization between patients who do and do not develop PSS in the UK. Methods: Adults registered in The Health Improvement Network database with a recorded stroke between 2007 and 2011 were included. PSS was identified through Read codes; machine learning was used to retrospectively identify unrecorded PSS events. Patients with diagnosed or predicted PSS in the 12 months after stroke were matched to those with no PSS on age, sex, number of strokes, socioeconomic status, and comorbidities using the nearest neighbor algorithm. Utilization and costs associated with general practitioner visits, nurse visits, hospitalizations, referrals to specialists, laboratory tests, and medications in the 12 months after stroke were compared. Results: Overall, 2,951 PSS cases were matched to 37,753 controls. During the first year, more PSS cases visited a physiotherapist (19% vs 7%) and occupational therapist (12% vs 5%) compared to controls. A greater proportion of cases were also referred to specialists (76% vs 64%) and hospitalized (33% vs 9%) compared to controls. Medication for spasticity was, on average, 14.68 prescriptions for cases and 5.64 for controls. Total mean costs per patient were £1,270 (standard deviation [SD] = 772) and £635 (SD = 273) for cases and controls, respectively. Conclusion: Costs after stroke for patients developing PSS are twice as high compared to patients who do not develop it, with the major driver being the number of hospital admissions. This highlights the need for better recording and closer management of PSS.

Background: Many established products (EPs – marketed for eight years or more) are widely used off-label despite little evidence on benefit–risk ratio. This exposes patients to risks related to safety and lack of efficacy, and healthcare providers to liability. Introducing new indications for EPs may represent a high societal value; however, manufacturers rarely invest in R&D for EPs. The objective of this research was to describe incentives and disincentives for developing new indications for EPs in Europe and to investigate consequences of current policies. Methods: Targeted literature search and expert panel meetings. Results: Within the current European-level and national-level regulatory framework there are limited incentives for development of new indications with EPs. Extension of indication normally does not allow the price to be increased or maintained, the market protection period to be extended, or exclusion from a reference price system. New indication frequently triggers re-evaluation, resulting in price erosion, regardless of the level of added value with the new indication. In consequence, manufacturers are more prone to undertake R&D efforts at early to mid-stage of product life cycle rather than with EPs, or to invest in new chemical entities, even in therapeutic areas with broad off-label use. This represents a potentially missed opportunity as developing new indications for EPs offers an alternative to off-label use or lengthy and expensive R&D for new therapies, opens new opportunities for potentially cost-effective treatment alternatives, as well as greater equity in patients’ access to treatment options. Conclusion: There are potential benefits from the development of new indications for EPs that are currently not being realized due to a lack of regulatory and pricing incentives in Europe. Incentives for orphan or paediatric drugs have proven to be effective in promoting R&D. Similarly, incentives to promote R&D in EPs should be developed, for the benefit of patients and healthcare systems.

Background To evaluate treatment effects of abobotulinumtoxinA in cervical dystonia (CD) using multilevel modelling and beta-binomial regression on different dimensions of the Short-Form-36 (SF-36) health-related quality-of-life questionnaire. Methods This study involved a post hoc analysis of patient-reported outcomes (PROs) from a Phase III, double-blind, randomised, placebo-controlled multicentre trial that had evaluated abobotulinumtoxinA's efficacy in patients with CD, including assessment using the SF-36 at baseline and 8 weeks. Multilevel modelling was used to explore between-centre and between-patient variability in these outcomes. In addition, the outcomes were assessed using beta-binomial regression, since this provides a good fit with the non-normal distribution of SF-36 data and allowed all eight health domains to be analysed by a single method. Results Compared with placebo, abobotulinumtoxinA produced significant improvement in the physical health component of SF-36 from baseline to week 8. Reduction in the physical health component score was associated with patients’ age ( p = 0.008), being male ( p = 0.009) and investigator's visual analogue scale for symptoms ( p = 0.006). The abobotulinumtoxinA group was 1.6 times more likely than the placebo group to show improvement in the physical functioning domain ( p = 0.01). Significant improvements for the role-emotional and mental health domains were 2.4 ( p = 0.0001) and 1.5 times ( p = 0.007) more likely with abobotulinumtoxinA than with placebo. Conclusions AbobotulinumtoxinA's clinical efficacy in relieving symptoms of CD is associated with significant HRQoL benefits. Compared with placebo, abobotulinumtoxinA therapy is associated with statistically significant improvements at week 8 on the physical health component of SF-36, as well as in the physical functioning, role-emotional and mental health domains.

Background: Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) are rare neoplasms. For innovative treatments, payer recommendations frequently involve sub-populations more restricted than approved indications. Paucity of epidemiologic data specific to sub-populations is a challenge for reimbursement strategies. Objectives: To estimate the population size by site and type of GEP-NETs in the US, EU, and Australia, over a five-year period. Methods: Two GEP-NET sub-populations, respectively approved and restricted indication for reimbursement, were considered: i) Stable/slow progressing well-differentiated, functioning and non-functioning GEP-NETs and unresectable locally advanced/metastatic disease; and ii) Stable/slow progressing well-differentiated, nonfunctioning GEP-NETs and unresectable locally advanced/metastatic disease. For both, tumours originating from the hindgut were excluded. Following identification in the literature of crude prevalence and incidence rates for a broader GEP-NET, estimates were obtained for each sub-population using proportions of GEP-NETs by site and type derived from clinical studies. Then, these figures were further refined using clinical expert opinions. A 5-year target population growth model was developed. Results: Over 5 years, respectively for the first and second sub-population, number of patients is expected to increase from 7,473 to 9,393 and 5,231 to 6,575 in selected European countries; from 8,051 to 10,119 and 5,636 to 7,083 in the US; and from 593 to 746 and 415 to 522 in Australia. Because the second sub-population is a subgroup of the first, lower estimates were obtained. Conclusion: In the absence of epidemiologic data on specific sub-populations, the development of a population growth model can be used to estimate trends in population size under varying labelling hypotheses.