Uncontrolled asthma: assessing quality of life and productivity of children and their caregivers using a cross-sectional Internet-based survey

<p>Abstract</p> <p>Background</p> <p>Results of a national survey of asthmatic children that evaluated management goals established in 2004 by the National Asthma Education and Prevention Program (NAEPP) indicated that asthma symptom control fell short on nearly every goal.</p> <p>Methods</p> <p>An Internet-based survey was administered to adult caregivers of children aged 6-12 years with moderate to severe asthma. Asthma was categorized as uncontrolled when the caregiver reported pre-specified criteria for daytime symptoms, nighttime awakening, activity limitation, or rescue medication based on the NAEPP guidelines. Children's health-related quality of life (HRQOL) and caregivers' quality of life (QOL) were assessed using the Child Health Questionnaire Parent Form 28 (CHQ-PF28) and caregiver's work productivity using a modified Work Productivity and Activity Impairment Questionnaire. Children with uncontrolled vs. controlled asthma were compared.</p> <p>Results</p> <p>360 caregivers of children with uncontrolled asthma and 113 of children with controlled asthma completed the survey. Children with uncontrolled asthma had significantly lower CHQ-PF28 physical (mean 38.1 vs 49.8, uncontrolled vs controlled, respectively) and psychosocial (48.2 vs 53.8) summary measure scores. They were more likely to miss school (5.5 vs 2.2 days), arrive late or leave early (26.7 vs 7.1%), miss school-related activities (40.6 vs 6.2%), use a rescue inhaler at school (64.2 vs 31.0%), and visit the health office or school nurse (22.5 vs 8.8%). Caregivers of children with uncontrolled asthma reported significantly greater work and activity impairment and lower QOL for emotional, time-related and family activities.</p> <p>Conclusions</p> <p>Poorly controlled asthma symptoms impair HRQOL of children, QOL of their caregivers, and productivity of both. Proper treatment and management to improve symptom control may reduce humanistic and economic burdens on asthmatic children and their caregivers.</p

Statistical Techniques for Analyzing Irregular and Sparse Cyclical Longitudinal Data with Applications to Bipolar Disorder

Bipolar disorder is an illness characterized by abnormal mood swings encompassing both mania and depression, often with irregular longitudinal patterns. The variable and cyclical episodic nature of the disease presents many challenges for statistical analyses. These complex features make it difficult to characterize the data, define disease improvement measures, and develop appropriate statistical models. This is particularly problematic among rapid cycling bipolar disorder patients whose disease is defined by highly erratic and frequent mood shifts. In this dissertation, I present two approaches to analyzing data from bipolar disorder studies. The first approach focuses on the time spent in various mood states. Using longitudinal mood severity rating scale scores, data are transformed into a sequence of mood states. These sequences are analyzed as a Markov chain and stationary distributions are used to measure within- and between-group differences. The non-parametric bootstrap is employed to test for differences. The second approach focuses on features of the mood episodes. Mood severity rating scale scores are modeled as a longitudinal function of episodes and patient-specific characteristics. Episodes are parameterized by their durations, peak severities (amplitudes), and times of occurrence (locations). This flexible parametric model is fit to the data using a global iterative search algorithm known as Particle Swarm Optimization. To reduce the dimensional space of the search algorithm, an episode detection method is proposed. Estimates are derived for each patient and are used as inputs in secondary statistical models. These approaches are applied to a three-arm randomized trial of rapid cycling bipolar disorder patients. Mechanisms of these approaches are tailored to address sparsity and small sample size issues present in the data. Simulations are used to assess the statistical performance and agreement of these approaches, and recommendations for clinical application are presented

Psychometric evaluation of the Worst Pruritus Numerical Rating Scale (NRS), Atopic Dermatitis Symptom Scale (ADerm-SS), and Atopic Dermatitis Impact Scale (ADerm-IS)

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus, skin pain, and sleep impacts, which are only reportable by patients themselves. The goal of this research is to evaluate the reliability, validity, and interpretability of the scores from three patient-reported outcome measures within the context of a clinical trial for adolescents and adults with moderate to severe AD. METHODS: Data from a Phase 3 randomized, double-blind, placebo-controlled, multinational clinical trial for individuals 12-75 years of age with moderate to severe AD (AD Up [ClinicalTrials.gov NCT03568318]) were used to assess the reliability, validity, and interpretability of scores on the Worst Pruritus Numerical Rating Scale (NRS) and the Atopic Dermatitis Symptom and Impact Scales (ADerm-SS and ADerm-IS). Analyses were conducted separately for the adult and adolescent subgroups. RESULTS: Of the 882 participants included in the psychometric analyses, the majority were adults ( = 769, 87.2%), male ( = 536, 60.8%), and white ( = 630, 71.4%). Multi-item scores from the ADerm-SS and ADerm-IS had good internal consistency reliability, and most scores demonstrated acceptable test-retest reliability. Scores from the three questionnaires demonstrated adequate validity, exhibiting correlations with other conceptually related outcome assessments and score differences between clinically distinct subgroups. Finally, the score interpretation analyses provide estimates for meaningful within-person change and between-groups difference thresholds that may be useful for future research in adults and adolescents with moderate to severe AD. CONCLUSIONS: These results provide evidence that the scores produced by the Worst Pruritus NRS, ADerm-SS, and ADerm-IS are reliable and construct-valid when completed by adults and adolescents with moderate to severe AD in a clinical trial setting. The results presented here expand upon the previous qualitative evidence of these tools and provide further support for their use in future clinical studies. While results are specific to clinical trials, next steps would be to evaluate the use of these questionnaires in clinical practice. This can provide clinicians and dermatologists a window into the patient\u27s disease experience outside of the clinic, aid in shared decision making, and support a patient-centric approach to management of moderate to severe AD

Achieving hidradenitis suppurativa response score is associated with significant improvement in clinical and patient-reported outcomes: Post hoc analysis of pooled data from PIONEER I and II

Hidradenitis Suppurativa Clinical Response (HiSCR), is a validated tool that has been used to assess the efficacy of adalimumab among patients with hidradenitis suppurativa. We evaluated the clinical meaning of HiSCR by relating it to patient-reported outcomes to give further context to its achievement in a post hoc analysis of integrated data from two phase 3 clinical trials (PIONEER I and II). Pooling placebo and active treatment arms, 39% of patients (245/629) achieved HiSCR at week 12. Irrespective of treatment, significantly (p < 0.05) more HiSCR responders than non-responders experienced clinically meaningful improvement in Dermatology Life Quality Index (60.5% vs 30.4%), Pain Numeric Rating Scale (46.9% vs 19.9%), hidradenitis suppurativa quality of life (49.4% vs 26.9%), work-related performance (52.6% vs 37.7%), and non-work-related performance (59.5% vs 33.3%). Clinically meaningful outcomes in hidradenitis suppurativa are more likely to be attained in patients achieving HiSCR level improvement

Adjunctive thyroid hormone treatment in rapid cycling bipolar disorder: A double‐blind placebo‐controlled trial of levothyroxine (L‐T4) and triiodothyronine (T3)

ObjectivesThis report describes the first comparative double-blind, placebo-controlled trial of levothyroxine (L-T4 ) and triiodothyronine (T3 ) as adjunctive treatments in rapid cycling bipolar disorder.MethodsThirty-two treatment-resistant, rapid cycling patients who had failed a trial of lithium were randomized into three treatment arms: L-T4 , T3 , or placebo. They were followed for ≥4&nbsp;months with weekly clinical and endocrine assessments.ResultsThere were no statistically significant differences between the groups in age, gender, duration of illness, or thyroid status. Markov chain analyses were employed to assess treatment effects on cycling patterns among mood states (euthymia, depression, mania, and mixed). Within groups, post-treatment the L-T4 group spent significantly less time depressed or in a mixed state and greater time euthymic. The T3 and placebo groups did not differ significantly pre- and post-treatment in any mood state, although the pattern of effects was the same for the T3 group as for the L-T4 group. Between groups, the L-T4 group had a significantly greater increase in time euthymic and decrease in time in the mixed state than the placebo group. Other group differences were not significant, although they were in the expected direction.ConclusionsThe findings in this first double-blind study directly comparing the effects of L-T4 and T3 therapy against placebo provide evidence for the benefit of adjunctive L-T4 in alleviating resistant depression, reducing time in mixed states and increasing time euthymic. Adjunctive T3 did not show statistically significant evidence of benefit over placebo in reducing the time spent in disturbed mood states

Determining Severity Strata for Three Atopic Dermatitis Patient-Reported Outcome Questionnaires: Defining Severity Score Ranges for the Worst Pruritus Numerical Rating Scale and the Atopic Dermatitis Symptom and Impact Scales (ADerm-SS and ADerm-IS)

INTRODUCTION: Three patient-reported outcome (PRO) questionnaires-Worst Pruritus Numerical Rating Scale (WP-NRS), Atopic Dermatitis Symptom Scale (ADerm-SS), and Atopic Dermatitis Impact Scale (ADerm-IS)-were developed to assess the symptoms and impacts of atopic dermatitis (AD). Severity strata for these PROs are needed to aid in their interpretation. METHODS: Using data from a global, randomized, double-blind, placebo-controlled, phase 3 clinical trial (NCT03568318) of patients with moderate-severe AD (age ≥ 12 years), equipercentile linking analyses were conducted to define severity strata applying the Patient Global Impression of Severity as an anchor. Analyses were conducted separately for adults and adolescents, and then harmonized between the two age groups. RESULTS: The sample included 769 adults and 113 adolescents. For the WP-NRS, 0 was associated with absent, 1-2 with minimal, 3 with mild, 4-7 with moderate, and 8-10 with severe. For the ADerm-SS Skin Pain, 0 was associated with absent, 1 with minimal, 2 with mild, 3-6 with moderate, and 7-10 with severe. For ADerm-SS 7-Item Total Symptom Score (TSS-7), 0-1 was associated with absent, 2-11 with minimal, 12-22 with mild, 23-47 with moderate, and 48-70 with severe. For ADerm-IS Sleep, 0 was associated with absent, 1-3 with minimal, 4-6 with mild, 7-20 with moderate, and 21-30 with severe. For ADerm-IS Daily Activities, 0 was associated with absent, 1-2 with minimal, 3-7 with mild, 8-25 with moderate, and 26-40 with severe. For ADerm-IS Emotional State, 0 was associated with absent, 1-2 with minimal, 3-8 with mild, 9-22 with moderate, and 23-30 with severe. CONCLUSIONS: These severity strata provide score interpretations of the WP-NRS, ADerm-SS, and ADerm-IS, translating these scores to simple and intuitive outcomes, which can inform clinical studies and clinical practice. TRIAL REGISTRATION NUMBER: NCT03568318

Determining Severity Strata for Three Atopic Dermatitis Patient-Reported Outcome Questionnaires: Defining Severity Score Ranges for the Worst Pruritus Numerical Rating Scale and the Atopic Dermatitis Symptom and Impact Scales (ADerm-SS and ADerm-IS)

INTRODUCTION: Three patient-reported outcome (PRO) questionnaires-Worst Pruritus Numerical Rating Scale (WP-NRS), Atopic Dermatitis Symptom Scale (ADerm-SS), and Atopic Dermatitis Impact Scale (ADerm-IS)-were developed to assess the symptoms and impacts of atopic dermatitis (AD). Severity strata for these PROs are needed to aid in their interpretation. METHODS: Using data from a global, randomized, double-blind, placebo-controlled, phase 3 clinical trial (NCT03568318) of patients with moderate-severe AD (age ≥ 12 years), equipercentile linking analyses were conducted to define severity strata applying the Patient Global Impression of Severity as an anchor. Analyses were conducted separately for adults and adolescents, and then harmonized between the two age groups. RESULTS: The sample included 769 adults and 113 adolescents. For the WP-NRS, 0 was associated with absent, 1-2 with minimal, 3 with mild, 4-7 with moderate, and 8-10 with severe. For the ADerm-SS Skin Pain, 0 was associated with absent, 1 with minimal, 2 with mild, 3-6 with moderate, and 7-10 with severe. For ADerm-SS 7-Item Total Symptom Score (TSS-7), 0-1 was associated with absent, 2-11 with minimal, 12-22 with mild, 23-47 with moderate, and 48-70 with severe. For ADerm-IS Sleep, 0 was associated with absent, 1-3 with minimal, 4-6 with mild, 7-20 with moderate, and 21-30 with severe. For ADerm-IS Daily Activities, 0 was associated with absent, 1-2 with minimal, 3-7 with mild, 8-25 with moderate, and 26-40 with severe. For ADerm-IS Emotional State, 0 was associated with absent, 1-2 with minimal, 3-8 with mild, 9-22 with moderate, and 23-30 with severe. CONCLUSIONS: These severity strata provide score interpretations of the WP-NRS, ADerm-SS, and ADerm-IS, translating these scores to simple and intuitive outcomes, which can inform clinical studies and clinical practice. TRIAL REGISTRATION NUMBER: NCT03568318